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>>WELCOME

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EVERYONE. IT IS A PLEASURE TO

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SEE YOU, ALL BEIT VIRTUALLY.

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THANK YOU FOR JOINING THIS ROUND

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TABLE, WE COULDN'T DO IT WITHOUT

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YOUR PARTICIPATION. AND THESE

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MEETINGS ARE VERY IMPORTANT TO

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NIAMS AS WE LEARN ABOUT EMERGING

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AREAS IN THE FIELD AND HOW WE

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MIGHT MAKE A DIFFERENCE. I WILL

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NOW TURN THE MEETING OVER TO THE

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NIAMS DIRECTOR DR. LINDSEY

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CRISWELL FOR OPENING REMAR REMA.

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DR. CRISWELL.

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>>THANK YOU, JONELLE.
GOOD

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MORNING EVERYONE, I'M DR. LINDS

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SHY CRISWELL, DIRECTOR NATIONAL

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INSTITUTE OF ARTHRITIS AND

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MUSCULOSKELETAL AND SKIN

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DISEASES. WELCOME Y'ALL TO OUR

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ROUND TABLE ON CARTILAGE

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PRESERVATION AND RESTORATION IN

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KNEE OSTEOARTHRITIS. WE ARE

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HOPING TODAY'S MEETING WILL HELP

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TO GENERATE ADDITIONAL INTEREST

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IN THE TOPIC OF CARTILAGE

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PRESERVATION RESTORATION AMONG

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THE NIAMS COMMUNITY AND TO THAT

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END THE MEETING IS BEING

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VIDEOCAST AND RECORDED AND WILL

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BE AVAILABLE FOR VIEWING ON THE

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NIH VIDEOCAST ARCHIVE. SO WE

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GREATLY APPRECIATE YOUR

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ATTENDANCE TODAY AS WELL AS --

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AS YOUR EFFORTS TO GATHER

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FEEDBACK FROM YOUR COLLEAGUES.

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THE INFORMATION YOU PROVIDED IN

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PREPARATION FOR THE ROUND TABLE

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HELPED TO SHAPE OUR AGENDA, AND

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WILL SUPPLEMENT TODAY'S

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DISCUSSION. I WANTED TO THANK

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DR. TED XANG FOR AGREEING TO

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LEAD THIS MEETING AND ORGANIZING

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THE ROUND TABLE HAS BEEN A TEAM

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EFFORT INVOLVING IN MEMBERS OF

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OUR INSTITUTE.  SO OUR DIVISION

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OF EXTRAMURAL RESEARCH I WOULD

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LIKE TO ESPECIALLY RECOGNIZE DR.

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GAIL LESTER WHO SERVES AS

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DIRECTOR OF THE DIVISION, DR.

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PAE, ANALYST RESPONSIBLE FOR

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MUCH OF THE BEHIND THE SCENES

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WORK AND PROGRAM DIRECTORS,

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INCLUDING DR. LEXI BELGUN, DR.

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ANTHONY, DR. MARKWITS AND DR.

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CHUCK WASHABAU. I WOULD ALSO

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LIKE TO RECOGNIZE STAFF FROM

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ANALYSIS POLICY PLANNING BRANCH

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WHO PLAYED KEY ROLES PUTTING

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THIS ROUND TABLE TOGETHER. DR.

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STEPHANIE BURRO, CHIEF OF THE

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BRANCH, DR. JONELLE DRUGAN, DR.

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VAN NGUYNEY AND DR. THOMAS

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JACKSON. BEFORE I GO OVER -- I

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WOULD LIKE TO PROCEED WITH

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INTRODUCTIONS BY THE GROUP. 

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FIRST DR. BOB CARTER WHO SERVES

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AS DEPUTY DIRECTOR OF THE

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INSTITUTE. I WANTED TO INVITE

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DR. CARTER TO SAY A FEW WORDS AT

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THIS TIME. BOB.

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>>GOOD MORNING. DELIGHTED
TO BE

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HERE WITH Y'ALL, PARTICULARLY

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OLD FRIENDS AND HOPEFULLY NEW

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FRIENDS. THIS HAS BEEN A LEONG

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TIME BIRTHING. WE HAVE BEEN

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WORKING ON THIS GOOD YEAR AND A

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HALF AT LEAST AND TED HAS BEEN

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IN THE MIDDLE AND APPRECIATE HIS

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WILLINGNESS TO WORK WITH US AND

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BE FLEXIBLE AND WORK WITH WHAT

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WE THINK IS AN EXCITING AGENDA.

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THERE'S AN AWFUL LOT TO TALK

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ABOUT WHEN IT COMES TO

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REGENERATIVE MEDICINE APPROACHES

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OR HOW TO PRESERVE CARTILAGE IN

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PATIENTS WITH OA. IT IS A HUGE

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AREA IT IS DIFFICULT AND FRAUGHT

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WITH PROBLEMS PARTICULARLY LOT

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OF THINGS GOING ON WHICH THERE

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IS NOT MUCH DATA ALSO ALL SORTS

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OF DIFFERENT THINGS BEING TRIED

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WITHOUT MUCH DOCUMENTATION WHAT

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THEY ARE. BUT I WANT TO INSTEAD

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OF FOCUSING ON THOSE PROBLEMS I

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HOPE WE CAN FOCUS TODAY ON WHAT

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THE HOPE IS. WHERE IS THE

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PROMISE, THE LIGHT THAT WE CAN

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SEE COMING? WHERE IS THE HOPE?

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WE THINK WE HAVE TO CHANGE HOW

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WE TREAT OA. WE CAN'T REPLACE

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THE KNEES AND ALL THE PEOPLE

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THAT NEED IT IN ANOTHER 10, 20

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YEARS, WE DESPERATELY NEED NEW

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WAYS TO REVERSE AND PREVENT

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REGRESSION OF OA. WHAT WE ARE

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DOING TODAY IS WHERE ARE THE

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POSSIBILITIES, HOW CAN WE --

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WHAT SHOULD WE THINK OF THE

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TERMS OF HOW WE ARE GOING TO GET

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THERE. SO HOPE WITH THAT FOCUS

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REALLY LOOKING FORWARD TO SOME

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LEARNING A LOT AND GOOD

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DISCUSSION AND THANK YOU FOR ALL

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FOR PARTICIPATING.

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>>THANKS, BOB. IT IS ALSO

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IMPORTANT FOR YOU TO KNOW THAT

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NOT ONLY ARE THE LEADERSHIP AND

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STAFF OF THE NIAMS PARTICIPATING

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IN THIS ROUND TABLE, BUT SINCE

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TODAY'S DISCUSSION INTERSECTS

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WITH THE PORTFOLIOS OF OTHER NIH

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AND HHS COMPONENTS, WE ASKED OUR

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COLLEAGUES TO JOIN US HERE

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TODAY. THUS WE ARE FORTUNATE TO

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HAVE REPRESENTATIVES FROM THE

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NATIONAL HEART LUNG AND BLOOD

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INSTITUTE. THE NATIONAL

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INSTITUTE OF DENTAL AND

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CRANIOFACIAL RESEARCH AND THE

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U.S. FOOD AND DRUG

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ADMINISTRATION. THEIR

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INFORMATION IS LISTED IN THE

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ROSTER AND THEY WILL INTRODUCE

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THEMSELVES SOON. NEXT I WILL ASK

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EACH PARTICIPANT IN THE MEETING

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TO INTRODUCE YOURSELF TO PROVIDE

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A SENSE OF THE BREADTH OF THIS

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GROUP THAT WE HAVE ASSEMBLED

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TODAY. IN THE INTEREST OF TIME,

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WE WON'T HAVE OTHER NIAMS STAFF

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LISTED ON THE ROASTER INTRODUCE

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THEMSELVES AT THIS TIME BUT ASK

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THEY INTRODUCE THEMSELVES WHEN

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SPEAKING. NOW WHEN DR. XING

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CALLS YOUR NAME UNMUTE AND SHARE

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YOUR NAME, INSTITUTION AND THE

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EXPERTISE RELEVANT TO TODAY'S

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DISCUSSION. TED. 

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>>GOOD MORNING, EVERYONE.
MY

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NAME IS TED, TED ZHENG, PROGRAM

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DIRECTOR OF NIAMS AND MY

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RESEARCH PORTFOLIO IS CLINICAL

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OSTEOARTHRITIS AND DIAGNOSTIC

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TOOLS. OVER THE LAST YEAR I

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WOULD LIKE TO TAKE THIS LEAD AND

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BEEN HAS BEEN PLEASURE TO WORK

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WITH EACH OF YOU TO PREPARE THIS

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ROUND TABLE MEETING. THANK YOU.

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I WANT TO THANK EVERY ONE OF YOU

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FOR PARTICIPATING TODAY'S

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MEETING. I'M GOING TO CALL YOUR

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NAME LIKE DR. CRISWELL SAID,

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JUST BRIEFLY STATE YOUR NAME,

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INSTITUTE AND AFFILIATION, ONE

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OR TWO SENTENCE TO HIGHLIGHT

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YOUR AREA OF EXPERTISE RELATED

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TO THE ROUND TABLE. I WILL START

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WITH CO-CHAIRS AND GO BY THE

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LIST. BASED ON ALPHABETIC ORDER

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OF YOUR LAST NAME. DR. CONSTANCE

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CHU PLEASE.

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>>HI, GOOD MORNING. I'M
CONNIE

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CHU, VICE CHAIR OF RESEARCH

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STANFORD UNIVERSITY. I'M

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ORTHOPEDIC MEDICINE SPORTS

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MEDICINE AND ARTHROSCOPY. ACTIVE

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RESEARCH IN NIH FUNDED WHERE I

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GOT MY START WITH NIH, FOR MORE

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THAN 20 YEARS IN JOINT

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PRESERVATION AND PREVENTION OF

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OSTEOARTHRITIS.

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>>THANK YOU. DR. SCOTT
RODEO.

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>>GOOD MORNING, FIRST
GOOD

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MORNING TO CONNI CONNIE. I'M SCT

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RODEO, ORTHOPEDIC SURGEON

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SPECIAL SURGERY NEW YORK CITY I

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COME AT THIS AS CLINICIAN AND

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SCIENTIST. I TAKE CARE OFFER

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ATHLETES IN GIANTS FOOTBALL

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TEAM, RESEARCH SIDE WE USE

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NUMBER OF ANIMAL MODELS TO STUDY

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POST TRAUMATIC OA TENDON

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LIGAMENT REPAIR, IS AS VICE

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CHAIR AT HHS SO I COME AS

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CLINICIAN AND SCIENTIST.

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>>THANK YOU, SCOTT.

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>>DR. DR. AMBIKP
BAJPAYEE.

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>>I HEAD THE MOLECULAR

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BIOELECTROSTATICS AND DRUG

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DEVELOPMENT WE ARE INTERESTED IN

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DESIGNING ELECTRICALLY CHARGED

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BIOMATERIALS FOR APPLICATIONS IN

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DRUG DELIVERY AND IMAGING OF

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NEGATIVELY CHARGED AVASCULAR

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TISSUES HARD TO PENETRATE. SO WE

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HAVE A SPECIAL FOCUS HERE ON

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CARTILAGE REPAIR AND TREATING

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OSTEOARTHRITIS FOR WHICH WE

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DESIGN SUSTAINED RELEASE

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THERAPIES USING CATIONIC

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PEPTIDES PROTEINS AND EXOSOMES. 

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HAPPY TO BE HERE. THANK YOU FOR

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INVITING ME. DR. BAJPAYEE.

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>>DR. FRANKS BARRY.

216
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>>I'M FRANK BARRY, MY
CURRENT

217
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AFFILIATION IS AS DIRECTOR OF

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THE TRANSLATIONAL MEDICINE

219
00:08:20,320 --> 00:08:23,080
INSTITUTE AT COLORADO STATE

220
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UNIVERSITY. MY AREA OF RESEARCH

221
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FOCUS IS MESENCHYMAL STROME A.M.

222
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CELL THERAPY DEVELOPMENT INST

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OWE ARTHRITIS AND CARTILAGE

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REPAIR. VERY MUCH WITH

225
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TRANSLATIONAL INTEREST AND VERY

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HAPPY TO BE PART OF THE

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DISCUSSION TODAY.

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>>THANK YOU. DR.
STEPHANIE

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BRYANT.

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>>GOOD MORNING. EVERYONE.
MY

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NAME IS STEPHANIE BRYANT, I'M

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HERE AT THE UNIVERSITY OF

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COLORADO BOULDER. I'M IN THE

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DEPARTMENT OF CHEMICAL AND

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BIOLOGICAL ENGINEERING AS WELL

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AS MATERIAL SCIENCE AND

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ENGINEERING. I'M AN HE CAN

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ENGINEER BY TRAINING. AND MY

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RESEARCH REALLY FOCUSES ON

240
00:09:01,880 --> 00:09:03,320
DESIGNING HYDRO GELS FOR

241
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PROMOTING CARTILAGE

242
00:09:04,760 --> 00:09:06,120
REGENERATION. I'M LOOKING

243
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FORWARD TO BEING PART OF THIS.

244
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THANK YOU SO MUCH.

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>>THANK YOU. OUR HEART
LUNG AND

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POLLUTE. DR. DENIS BUXTON

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PLEASE.

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>>GOOD MORNING, I'M DENII

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BUXTON, DIVISION OF

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CARDIOVASCULAR SCIENCE. I LEAD

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THE NHLBI PROGENITOR CELL

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BIOLOGY TRANSLATIONAL CONSOR 

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CONSORTIUM. AND ALSO MUCH --

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SOME OF THE CLINICAL TRIALS IN

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CELL THERAPY FOR NHLBI.

256
00:09:36,880 --> 00:09:42,760
>>THANK YOU. SO DR.
JENNIFER

257
00:09:42,760 --> 00:09:47,720
ELISSEEFF. MY NAME IS JENNIFER

258
00:09:47,720 --> 00:09:49,200
ELISSEEFF, BIOMEDICAL

259
00:09:49,200 --> 00:09:50,760
ENGINEERING JOHNS HOPKINS AND

260
00:09:50,760 --> 00:09:52,400
WORK ON STEM CELLS AN HYDRO GELS

261
00:09:52,400 --> 00:09:54,960
FOR CARTILAGE REPAIR AND NOW

262
00:09:54,960 --> 00:09:56,680
MOVING TO SENESCENCE AND

263
00:09:56,680 --> 00:10:00,680
INFLAMMATION PATHWAYS ASSOCIATED

264
00:10:00,680 --> 00:10:01,640
WITH OSTEOARTHRITIS AND

265
00:10:01,640 --> 00:10:02,680
CARTILAGE DAMAGE. NICE TO BE

266
00:10:02,680 --> 00:10:05,880
HERE. THANK YOU.

267
00:10:05,880 --> 00:10:15,080
>>DR. ANDREAS GOMOLL.

268
00:10:15,080 --> 00:10:19,520
LOOKS LIKE WE ARE MISSING HIM.

269
00:10:19,520 --> 00:10:22,280
>>I DON'T THINK HE'S ON.

270
00:10:22,280 --> 00:10:25,320
>>DR. DANIEL GRANDE.

271
00:10:25,320 --> 00:10:27,480
>>GOOD MORNING, EVERYONE.
I'M

272
00:10:27,480 --> 00:10:31,080
DANIEL GRANDE, SCIENTIST, I'M AT

273
00:10:31,080 --> 00:10:32,240
NORTH WELL HEALTH NEW YORK,

274
00:10:32,240 --> 00:10:33,360
DEPARTMENT OF ORTHOPEDIC

275
00:10:33,360 --> 00:10:35,040
SURGERY. I'M INTERESTED IN MANY

276
00:10:35,040 --> 00:10:37,280
CARTILAGE REPAIR FOR A LEONG

277
00:10:37,280 --> 00:10:41,840
TIME AT THIS POINT. ALSO WE HAVE

278
00:10:41,840 --> 00:10:43,720
A ACTIVE PROGRAM IN REGENERATIVE

279
00:10:43,720 --> 00:10:45,520
MEDICINE HERE. THANK YOU.

280
00:10:45,520 --> 00:10:47,880
>>THANK YOU.

281
00:10:47,880 --> 00:10:50,120
>>DR. FARSHID GUILAK.

282
00:10:50,120 --> 00:10:53,080
>>I'M FARSHID GUILAK.

283
00:10:53,080 --> 00:10:54,160
WASHINGTON UNIVERSITY ST. LOUIS

284
00:10:54,160 --> 00:10:56,080
AND SHRINERS HOSPITALS FOR

285
00:10:56,080 --> 00:10:57,600
CHILDREN IN ST. LOUIS AND MY

286
00:10:57,600 --> 00:11:01,040
RESEARCH IS FOCUSED ON MOSTLY

287
00:11:01,040 --> 00:11:05,240
OSTOSTEOARTHRITIS,S AND RHEUMATD

288
00:11:05,240 --> 00:11:06,400
ARTHRITIS AND DEVELOPING

289
00:11:06,400 --> 00:11:07,840
CELLULAR TISSUE ENGINEERING

290
00:11:07,840 --> 00:11:10,200
THERAPIES TO TREAT THEM AND MOST

291
00:11:10,200 --> 00:11:11,440
RECENTLY I'LL PRESENT TODAY ON

292
00:11:11,440 --> 00:11:13,800
THE APPLICATION OF SYNTHETIC

293
00:11:13,800 --> 00:11:16,520
BIOLOGY TO REPROGRAM STEM CELLS

294
00:11:16,520 --> 00:11:17,960
AS DRUG DELIVERY VEHICLES FOR

295
00:11:17,960 --> 00:11:19,840
ARTHRITIS.

296
00:11:19,840 --> 00:11:24,160
>>THANK YOU. DR. MARK
HOCHBERG

297
00:11:24,160 --> 00:11:29,160
>>GOOD MORNING. I'M
PROFESSOR

298
00:11:29,160 --> 00:11:31,160
OF MEDICINE EPIDEMIOLOGY PUBLIC

299
00:11:31,160 --> 00:11:32,320
HEALTH UNIVERSITY OF MARYLAND

300
00:11:32,320 --> 00:11:35,200
SCHOOL OF MEDICINE IN BALTIMORE 

301
00:11:35,200 --> 00:11:37,080
AND DIRECTOR OF THE MEDICAL CARE

302
00:11:37,080 --> 00:11:38,880
CLINICAL CENTER FOR THE VA

303
00:11:38,880 --> 00:11:40,240
MARYLAND HEALTHCARE SYSTEM. AND

304
00:11:40,240 --> 00:11:44,200
YOU SEE THE BALTIMORE VA MEDICAL

305
00:11:44,200 --> 00:11:47,320
CENTER BEHIND ME ME. I WORKED IN

306
00:11:47,320 --> 00:11:49,120
THE FIELD OF OSTEOARTHRITIS

307
00:11:49,120 --> 00:11:52,120
CLINICAL EPIDEMIOLOGIC RESEARCH

308
00:11:52,120 --> 00:11:56,880
FOR ABOUT 40 YEARS. AND I WILL

309
00:11:56,880 --> 00:11:58,520
BE TALKING ON SMALL MOLECULES

310
00:11:58,520 --> 00:12:00,160
FOR CARTILAGE REGENERATION,

311
00:12:00,160 --> 00:12:02,400
SOMETHING FOR WHICH I HAVE NO

312
00:12:02,400 --> 00:12:06,360
PERSONAL EXPERIENCE.

313
00:12:06,360 --> 00:12:12,440
>>THANK YOU, MARK. DR.
JOHNNY

314
00:12:12,440 --> 00:12:12,640
HUARD.

315
00:12:12,640 --> 00:12:16,640
>>I'M JOHNNY HUARD, CHIEF

316
00:12:16,640 --> 00:12:19,720
OFFICER OF THE STEADMAN

317
00:12:19,720 --> 00:12:22,320
PHILIPPON RESEARCH INSTITUTE AND

318
00:12:22,320 --> 00:12:23,320
DIRECTOR OF MEDICINE PROGRAM

319
00:12:23,320 --> 00:12:24,840
HERE IN VAIL, COLORADO. I HAVE

320
00:12:24,840 --> 00:12:26,480
BEEN WORKING ON STEM CELL

321
00:12:26,480 --> 00:12:27,840
THERAPY FOR OSTEOARTHRITIS FOR A

322
00:12:27,840 --> 00:12:30,040
WHILE NOW AND I'M ALSO INVOLVED

323
00:12:30,040 --> 00:12:34,760
IN BIOLOGICAL APPROACH TO REDUCE

324
00:12:34,760 --> 00:12:37,120
INFLAMMATION TO ALIENATION OF

325
00:12:37,120 --> 00:12:39,080
SENESCENCE CELLS AND DEVELOPING

326
00:12:39,080 --> 00:12:40,360
BLOOD FIBROSIS APPROACH. THANK

327
00:12:40,360 --> 00:12:41,240
YOU FOR HAVING ME.

328
00:12:41,240 --> 00:12:51,800
>>AND OUR FROM FDA. DR.
LARISSA

329
00:12:52,280 --> 00:12:52,480
LAPTEVA,

330
00:12:52,480 --> 00:12:54,360
>>TISSUES ADVANCED
THERAPIES IN

331
00:12:54,360 --> 00:12:56,360
THE CENTER FOR BIOLOGICS

332
00:12:56,360 --> 00:12:58,040
EVALUATION RESEARCH AT THE FOOD

333
00:12:58,040 --> 00:13:00,360
AND DRUG ADMINISTRATION. IN

334
00:13:00,360 --> 00:13:02,160
ADDITION TO THAT MAYBE MORE

335
00:13:02,160 --> 00:13:04,000
IMPORTANTLY I'M ALSO

336
00:13:04,000 --> 00:13:05,920
RHEUMATOLOGIST, BORN AND RAISED

337
00:13:05,920 --> 00:13:09,360
IN NIAMS, MORE THAN 20 YEARS AGO

338
00:13:09,360 --> 00:13:11,440
WHERE I FINISHED FELLOWSHIP AND

339
00:13:11,440 --> 00:13:12,800
WORKED AS A CLINICAL

340
00:13:12,800 --> 00:13:13,880
INVESTIGATOR FOR A WHILE AND

341
00:13:13,880 --> 00:13:19,840
THEN MOVED TO FDA. I'M ALSO

342
00:13:19,840 --> 00:13:22,600
COMBINING MY WORK AT THE AGENCY

343
00:13:22,600 --> 00:13:24,840
WITH THE CLINICAL CARE IN THE

344
00:13:24,840 --> 00:13:26,960
RHEUMATOLOGY CLINIC IN NIAMS UP

345
00:13:26,960 --> 00:13:28,200
UNTIL THIS DAY. LOOKING FORWARD

346
00:13:28,200 --> 00:13:30,360
TO THE DISCUSSION. THANK YOU FOR

347
00:13:30,360 --> 00:13:31,600
INVITING ME.

348
00:13:31,600 --> 00:13:35,800
>>GLAD TO HAVE YOU BACK,

349
00:13:35,800 --> 00:13:39,480
LARISSA. DR. CHRISTIAN

350
00:13:39,480 --> 00:13:43,560
LATTERMANN PLEASE. 

351
00:13:43,560 --> 00:13:46,440
>>AMYE LEONG. YOU ARE
NEXT.

352
00:13:46,440 --> 00:13:50,320
>>GOOD MORNING, EVERYONE.
AMYE

353
00:13:50,320 --> 00:13:53,440
LEONG FROM SANTA BARBARA,

354
00:13:53,440 --> 00:13:55,840
CALIFORNIA PRESIDENT AND CEO OF

355
00:13:55,840 --> 00:13:57,920
HEALTHY MOTIVATION. MY CHARGE IS

356
00:13:57,920 --> 00:13:59,600
TO BRING TO YOU AND OTHERS

357
00:13:59,600 --> 00:14:01,120
PATIENT PERSPECTIVE, A PATIENT

358
00:14:01,120 --> 00:14:05,200
PERSPECTIVE ON THIS. IT HAS

359
00:14:05,200 --> 00:14:08,600
STARTED LIKE SOME OTHERS, BORN

360
00:14:08,600 --> 00:14:11,480
OUT OF NIAMS EARLY, EARLY ON AT

361
00:14:11,480 --> 00:14:14,560
THE START OF NIAMS ACTUALLY. DR.

362
00:14:14,560 --> 00:14:17,080
STEVEN KATZ AND I STARTED

363
00:14:17,080 --> 00:14:20,680
TOGETHER, THE SAME YEAR HE AS

364
00:14:20,680 --> 00:14:23,920
DIRECTOR AND MYSELF AS APPOINTED

365
00:14:23,920 --> 00:14:26,840
TO THIS NIAMS STEERING COMMITTEE

366
00:14:26,840 --> 00:14:28,400
ADVISORY COMMITTEE. DELIGHTED TO

367
00:14:28,400 --> 00:14:32,280
BE HERE. I BRING THE PERSPECTIVE

368
00:14:32,280 --> 00:14:36,240
OF A LIFE LIVED FOR A LEONG,

369
00:14:36,240 --> 00:14:38,960
LEONG TIME WITH VARIOUS FORMS OF

370
00:14:38,960 --> 00:14:40,880
ARTHRITIS, ULTIMATELY

371
00:14:40,880 --> 00:14:43,360
CULMINATING IN OA. I FIND IT

372
00:14:43,360 --> 00:14:47,680
VERY INTERESTING THESE GROUPS OF

373
00:14:47,680 --> 00:14:49,600
MEDICINE OR DISEASES ARE CLUMPED

374
00:14:49,600 --> 00:14:52,360
SO CLOSELY TOGETHER THAT WE

375
00:14:52,360 --> 00:14:54,800
PATIENTS AND THE PATIENT WORLD,

376
00:14:54,800 --> 00:14:56,040
PUBLIC WORLD OF IT IS SO

377
00:14:56,040 --> 00:14:58,040
CONFUSED BY THAT. SO I'M LOOKING

378
00:14:58,040 --> 00:15:00,120
FORWARD TO BRINGING THIS

379
00:15:00,120 --> 00:15:02,680
MESSAGE, MY BUSINESS BACKGROUND

380
00:15:02,680 --> 00:15:06,640
IS IN ORGANIZATIONAL DEVELOPMENT

381
00:15:06,640 --> 00:15:07,960
STRUCTURE ADVOCACY

382
00:15:07,960 --> 00:15:09,120
COMMUNICATIONS, PROCESSES AND I

383
00:15:09,120 --> 00:15:10,520
HOPE THAT CAN BE HELPFUL TO

384
00:15:10,520 --> 00:15:11,320
Y'ALL. THANK YOU.

385
00:15:11,320 --> 00:15:13,560
>>THANK YOU, AMYE.

386
00:15:13,560 --> 00:15:24,040
>>DR. CAROLYN LUTZKO. I
SAW

387
00:15:26,720 --> 00:15:35,120
YOUR NAMES HERE. DR. MICHAEL

388
00:15:35,120 --> 00:15:35,360
MONT.

389
00:15:35,360 --> 00:15:37,520
>>OKAY. THANK YOU, TED
AND

390
00:15:37,520 --> 00:15:38,920
THANK YOU, EVERYONE, CERTAINLY

391
00:15:38,920 --> 00:15:43,960
AN HONOR TO BE HERE. SO I'M AN

392
00:15:43,960 --> 00:15:46,720
ORTHOPEDIC SURGEON AT SINAI

393
00:15:46,720 --> 00:15:48,600
HOSPITAL AT BALTIMORE, WHERE I

394
00:15:48,600 --> 00:15:50,720
DO MY CLINICAL WORK. I'M ALSO

395
00:15:50,720 --> 00:15:54,160
THE DIRECTOR OF CLINICAL STUDIES

396
00:15:54,160 --> 00:15:56,000
AT NORTH WELL IN THE SAME SYSTEM

397
00:15:56,000 --> 00:15:59,200
AS DANIEL GRANDE WHO JUST

398
00:15:59,200 --> 00:16:01,400
PRESENTED HIMSELF. I'M WELL

399
00:16:01,400 --> 00:16:06,600
KNOWN FOR -- I HAVE ONE OR TWO

400
00:16:06,600 --> 00:16:08,360
NIH GRANTS ON THE FIELD OF

401
00:16:08,360 --> 00:16:11,800
AVASCULAR NECROSIS OR OSTEO

402
00:16:11,800 --> 00:16:14,000
NECROSIS CO-HEADS WITH STANFORD

403
00:16:14,000 --> 00:16:17,320
AND HOPKINS BUT WE ARE FROM MY

404
00:16:17,320 --> 00:16:18,920
WHOLE CAREER WE HAVE BEEN DOING

405
00:16:18,920 --> 00:16:22,240
CLINICAL STUDIES OF VARIOUS

406
00:16:22,240 --> 00:16:25,880
INJEINJECTABLES FOR TREATMENT OF

407
00:16:25,880 --> 00:16:27,760
KNEE OSTEOARTHRITIS.  WE HAVE

408
00:16:27,760 --> 00:16:29,640
FOUR OR FIVE CLINICAL STUDIES

409
00:16:29,640 --> 00:16:31,720
ONGOING RIGHT NOW. SO REALLY

410
00:16:31,720 --> 00:16:33,720
LOOKING FORWARD TO THIS PROGRAM,

411
00:16:33,720 --> 00:16:35,680
I LIKE DOING HIP AND KNEE

412
00:16:35,680 --> 00:16:37,160
REPLACEMENTS BUT IT IS MY LIFE

413
00:16:37,160 --> 00:16:38,480
LEONG PASSION TO SAVE PEOPLE

414
00:16:38,480 --> 00:16:40,280
FROM NEEDING THOSE PROCEDURES.

415
00:16:40,280 --> 00:16:43,280
WELCOME, EVERYONE. THANK YOU.

416
00:16:43,280 --> 00:16:49,360
>>THANK YOU. DR. GEORGE

417
00:16:49,360 --> 00:16:49,680
MUSCHLER,

418
00:16:49,680 --> 00:16:53,240
>>PLEASURE TO JOIN TODAY
I'M

419
00:16:53,240 --> 00:16:57,400
GEORGE MUSCHLER, ORTHOPEDIC

420
00:16:57,400 --> 00:16:59,080
SURGEON AND BIOPROFESSIONAL

421
00:16:59,080 --> 00:17:01,640
ENGINEER AT CLEVELAND CLINIC. MY

422
00:17:01,640 --> 00:17:02,760
CLINICAL PRAXIS IS ONCOLOGY BUT

423
00:17:02,760 --> 00:17:05,160
HOW HIP AND KNEE ARTHROPLASTY

424
00:17:05,160 --> 00:17:06,480
AND RUN THE JOINT RESERVATION

425
00:17:06,480 --> 00:17:09,040
CENTER WHERE WE HAVE ONGOING

426
00:17:09,040 --> 00:17:10,800
CLINICAL TRIALS AND REGISTRY TO

427
00:17:10,800 --> 00:17:12,600
LOOK AT EFFICACY OF BIOLOGICS.

428
00:17:12,600 --> 00:17:15,000
MY RESEARCH BACKGROUND IS

429
00:17:15,000 --> 00:17:19,400
STARTED IN HARVEST AND ISOLATION

430
00:17:19,400 --> 00:17:21,400
AND QUANTITATIVE METRICS TO

431
00:17:21,400 --> 00:17:22,520
MEASURE PERFORMANCE OF CELL

432
00:17:22,520 --> 00:17:23,960
POPULATIONS AVAILABLE TO US FROM

433
00:17:23,960 --> 00:17:26,840
BONE MARROW AND BONE. HELPING

434
00:17:26,840 --> 00:17:28,160
WITH STANDARDS DEVELOPMENT IN

435
00:17:28,160 --> 00:17:32,520
THAT AREA. AND RECENTLY

436
00:17:32,520 --> 00:17:33,520
DEVELOPING A PLATFORM FOR

437
00:17:33,520 --> 00:17:34,920
AUTOMATION OF IMAGE PROCESSING

438
00:17:34,920 --> 00:17:39,280
AND CELL PROCESSING FOR MSC AND

439
00:17:39,280 --> 00:17:42,640
IPS CELLS AS SOURCE FOR

440
00:17:42,640 --> 00:17:45,680
CARTILAGE. '

441
00:17:45,680 --> 00:17:47,960
>>THANK YOU. OUR
COLLEAGUE FROM

442
00:17:47,960 --> 00:17:48,880
NIDCR.

443
00:17:48,880 --> 00:17:51,640
>>HELLO. THANK YOU FOR
THE

444
00:17:51,640 --> 00:17:54,960
INVITATION TO PARTICIPATE IN

445
00:17:54,960 --> 00:17:56,920
THIS ROUND TABLE DISCUSSION. I'M

446
00:17:56,920 --> 00:17:59,360
SENIOR INVESTIGATOR AT THE NIDCR

447
00:17:59,360 --> 00:18:03,480
ON THE NIH CAMPUS AND I WORK ON

448
00:18:03,480 --> 00:18:05,480
SKELETAL STEM CELLS. MY LAB

449
00:18:05,480 --> 00:18:07,640
FOCUSES ON CHARACTERIZING THESE

450
00:18:07,640 --> 00:18:12,240
CELLS. DETERMINING THE ROLE THEY

451
00:18:12,240 --> 00:18:13,400
PLAY IN DISEASE, IN PARTICULAR

452
00:18:13,400 --> 00:18:16,040
HOW TO USE NECESSARY CELLS IN

453
00:18:16,040 --> 00:18:18,480
SKELETAL REGENERATION.

454
00:18:18,480 --> 00:18:21,840
>>THANK YOU. DR. DANIEL
SARIS.

455
00:18:21,840 --> 00:18:23,520
>>GOOD MORNING,
EVERYBODY.

456
00:18:23,520 --> 00:18:25,720
THANK YOU FOR THE INVITATION AND

457
00:18:25,720 --> 00:18:27,560
I FEEL HONORED AND EXCITED TO BE

458
00:18:27,560 --> 00:18:28,920
PART OF THIS ROUND TABLE. MY

459
00:18:28,920 --> 00:18:31,920
NAME IS DANIEL SARIS, ORTHOPEDIC

460
00:18:31,920 --> 00:18:34,000
SURGEON IN ROCHESTER, MINNESOTA

461
00:18:34,000 --> 00:18:36,320
MAYO CLINIC. THE LARGER PART WAS

462
00:18:36,320 --> 00:18:38,160
IN THE NETHERLANDS WHERE WE RAN

463
00:18:38,160 --> 00:18:40,280
THE TRIALS THAT LED TO CELL

464
00:18:40,280 --> 00:18:42,720
THERAPY REGISTRATION IN THE EMA

465
00:18:42,720 --> 00:18:44,320
AND THE FDA SPACE FOR CARTILAGE

466
00:18:44,320 --> 00:18:48,040
REPAIR. I MOVE TO MINNESOTA IN

467
00:18:48,040 --> 00:18:49,800
2018 AND BECAME PROFESSOR OF

468
00:18:49,800 --> 00:18:51,440
REGENERATIVE MEDICINE AT MAYO

469
00:18:51,440 --> 00:18:53,800
CLINIC. I RUN THE ORTHOPEDIC

470
00:18:53,800 --> 00:18:55,960
SPORTS MEDICINE RESEARCH AND

471
00:18:55,960 --> 00:18:57,200
CARTILAGE BIOLOGY TRANSLATIONAL

472
00:18:57,200 --> 00:19:00,480
LAB AND WE ARE FORTUNATE TO HAVE

473
00:19:00,480 --> 00:19:03,120
INDs OPEN FOR CELL BASED JOINT

474
00:19:03,120 --> 00:19:04,400
PRESERVATION I FEEL STRONGLY

475
00:19:04,400 --> 00:19:07,080
ABOUT FROM A PERSONAL, FROM

476
00:19:07,080 --> 00:19:08,160
PROFESSIONAL PERSPECTIVE AND

477
00:19:08,160 --> 00:19:09,360
HAVING BEEN PAST PRESIDENT OF

478
00:19:09,360 --> 00:19:11,400
THE INTERNATIONAL CARTILAGE

479
00:19:11,400 --> 00:19:12,560
REPAIR AND JOINT PRESERVATION

480
00:19:12,560 --> 00:19:14,000
SOCIETY. LOOK FORWARD TO TODAY,

481
00:19:14,000 --> 00:19:15,120
THANKS FOR THE INVITE.

482
00:19:15,120 --> 00:19:19,120
>>THANK YOU. DR. SHANE
SHAPIRO.

483
00:19:19,120 --> 00:19:21,920
>>I'M SHANE SHAPIRO, I
WORK AT

484
00:19:21,920 --> 00:19:24,920
MAYO CLINIC SOUTHERN CAMPUS IN

485
00:19:24,920 --> 00:19:27,840
FLORIDA. I'M CLINICIAN AND

486
00:19:27,840 --> 00:19:29,440
SCIENTIST, A MEDICAL ORTHOPEDIST

487
00:19:29,440 --> 00:19:30,840
IN SPORTS MEDICINE PHYSICIAN,

488
00:19:30,840 --> 00:19:34,720
HAVE BEEN USING INJECTABLE

489
00:19:34,720 --> 00:19:38,920
BIOLOGICS AND NON-CELLULAR

490
00:19:38,920 --> 00:19:39,600
REGENERATIVE THERAPIES FOR A

491
00:19:39,600 --> 00:19:41,960
NUMBER OF YEARS AND CONDUCTING

492
00:19:41,960 --> 00:19:44,640
TRANSLATIONAL STUDIES, SOME

493
00:19:44,640 --> 00:19:45,960
RANDOMIZED CLINICAL TRIALS, AND

494
00:19:45,960 --> 00:19:48,320
ALSO DISCOVERY SCIENCE WHERE WE

495
00:19:48,320 --> 00:19:50,840
PARTNERED WITH COLLEAGUES IN

496
00:19:50,840 --> 00:19:54,720
MULTIPLE DISCIPLINES LOOKING AT

497
00:19:54,720 --> 00:19:56,680
EXTRA CELLULAR VESICALES.  AS

498
00:19:56,680 --> 00:20:01,080
SUCH I HAVE FILED EIGHT FDA

499
00:20:01,080 --> 00:20:03,960
INDs FOR NOVEL REGENERATIVE

500
00:20:03,960 --> 00:20:05,240
THERAPIES, AND LOOKING FORWARD

501
00:20:05,240 --> 00:20:06,440
TO THIS GREAT DISCUSSION, THANK

502
00:20:06,440 --> 00:20:09,240
YOU FOR HAVING ME. I TOO GOT MY

503
00:20:09,240 --> 00:20:11,320
START AT THE NIH AS AN

504
00:20:11,320 --> 00:20:14,120
INTRAMURAL RESEARCH TRAINEE AT

505
00:20:14,120 --> 00:20:15,640
NHGRI AS PART OF THE HUMAN

506
00:20:15,640 --> 00:20:17,400
GENOME PROJECT. COUPLE OF

507
00:20:17,400 --> 00:20:19,800
DECADES AGO. SO NICE TO BE BACK

508
00:20:19,800 --> 00:20:21,120
AND PARTICIPATING.

509
00:20:21,120 --> 00:20:26,320
>>THANK YOU. DR. DAN
WHITE.

510
00:20:26,320 --> 00:20:28,120
>>GOOD MORNING. CERTAINLY
AN

511
00:20:28,120 --> 00:20:29,880
HONOR TO BE HERE. I AM A

512
00:20:29,880 --> 00:20:31,520
PHYSICAL THERAPIST AND ASSOCIATE

513
00:20:31,520 --> 00:20:33,960
PROFESSOR AT THE UNIVERSITY OF

514
00:20:33,960 --> 00:20:38,000
DELAWADELAWARE. MY MANGER OF STS

515
00:20:38,000 --> 00:20:39,760
PHYSICAL ACTIVITY IN SEDENTARY

516
00:20:39,760 --> 00:20:41,240
BEHAVIOR USING MONITORING

517
00:20:41,240 --> 00:20:43,680
DEVICES AND WE DO THESE STUDIES

518
00:20:43,680 --> 00:20:45,440
TYPICALLY IN LARGE COHORT

519
00:20:45,440 --> 00:20:47,720
STUDIES AND WE HAVE AS WELL AS

520
00:20:47,720 --> 00:20:49,400
CLINICAL TRIALS AND CURRENTLY I

521
00:20:49,400 --> 00:20:51,760
HAVE A FDA ASKED ME TO DO AN IDE

522
00:20:51,760 --> 00:20:54,080
WHICH WE GOT APPROVED TO LOOK AT

523
00:20:54,080 --> 00:20:56,840
STEM CELLS, MESENCHYMAL STEM

524
00:20:56,840 --> 00:20:58,320
CELLS FROM BONE MARROW ASPIRATE

525
00:20:58,320 --> 00:21:01,560
AND LOOKING AT CHANGES IN

526
00:21:01,560 --> 00:21:03,960
PHYSICAL ACTIVITY FROM THIS IN

527
00:21:03,960 --> 00:21:05,760
PEOPLE WITH KNEE OSTEOARTHRITIS.

528
00:21:05,760 --> 00:21:07,280
ALSO LIKE TO CONGRATULATE SCOTT

529
00:21:07,280 --> 00:21:10,080
RODEO WITH THE TWO AND 0 GIANTS

530
00:21:10,080 --> 00:21:11,200
START FIRST FILE IN A LEONG TIME

531
00:21:11,200 --> 00:21:12,320
SO THANK YOU FOR HELPING THE

532
00:21:12,320 --> 00:21:14,000
TEAM WITH THAT.

533
00:21:14,000 --> 00:21:19,720
>>LEONG SEASON. 

534
00:21:19,720 --> 00:21:23,440
>>DR. LATTERMANN JOIN US.

535
00:21:23,440 --> 00:21:25,120
>>HELLO, GOOD MORNING.

536
00:21:25,120 --> 00:21:26,880
APOLOGIZE FOR THE DELAY. I HAD

537
00:21:26,880 --> 00:21:30,400
TO GET MY POWERPOINT. MY NAME IS

538
00:21:30,400 --> 00:21:33,040
CHRISTIAN LATTERMANN CHIEF OF

539
00:21:33,040 --> 00:21:34,680
SPORTS BRIGHAM WOMEN'S HOSPITAL

540
00:21:34,680 --> 00:21:36,800
IN BOSTON AND DIRECTOR FOR MASS

541
00:21:36,800 --> 00:21:38,600
GENERAL BRIGHAM. MY RESEARCH

542
00:21:38,600 --> 00:21:40,640
INTERESTS ARE IN CLINICAL TRIALS

543
00:21:40,640 --> 00:21:43,560
IN CARTILAGE REPAIR AND ORTHO

544
00:21:43,560 --> 00:21:45,480
BIOLOGICS AS WELL AS IN BASIC

545
00:21:45,480 --> 00:21:48,640
SCIENCE. THE ETIOLOGY OF POST

546
00:21:48,640 --> 00:21:49,520
TRAUMATIC OSTEOARTHRITIS,

547
00:21:49,520 --> 00:21:50,440
PARTICULARLY WITH FOCUS ON

548
00:21:50,440 --> 00:21:53,440
INFLAMMATION. GOOD MORNING. GLAD

549
00:21:53,440 --> 00:21:54,720
TO BE PART OF THIS.

550
00:21:54,720 --> 00:21:58,200
>>THANK YOU FOR JOINING
US.  

551
00:21:58,200 --> 00:22:04,360
ALSO CAROLYN LUTZKO.

552
00:22:04,360 --> 00:22:06,080
>>GOOD MORNING. I
APOLOGIZE,

553
00:22:06,080 --> 00:22:06,920
HAVING SOME TECHNICAL TROUBLE

554
00:22:06,920 --> 00:22:12,440
HERE. BUT I AM A PROFESSOR

555
00:22:12,440 --> 00:22:13,840
PEDIATRICS AT UNIVERSITY OF

556
00:22:13,840 --> 00:22:15,240
CINCINNATI, IN CINCINNATI

557
00:22:15,240 --> 00:22:18,200
CHILDREN'S HOSPITAL. MY AREA OF

558
00:22:18,200 --> 00:22:19,920
RESEARCH IS CELL AN GENE

559
00:22:19,920 --> 00:22:23,080
THERAPY. FOCUSED ON

560
00:22:23,080 --> 00:22:25,160
MANUFACTURING AND PREPARATION OF

561
00:22:25,160 --> 00:22:28,320
CELL PRODUCTS EXVIVO FOR PHASE 1

562
00:22:28,320 --> 00:22:29,760
AND 2 CLINICAL TRIALS. 

563
00:22:29,760 --> 00:22:35,160
>>THANK YOU, CAROLYN. DR.

564
00:22:35,160 --> 00:22:40,440
CRISWELL, HAPPY TO REPORT ALL

565
00:22:40,440 --> 00:22:44,600
PARTICIPANTS EXCEPT DR. GOMOLL

566
00:22:44,600 --> 00:22:45,160
PRESENT. BACK TO YOU.

567
00:22:45,160 --> 00:22:47,520
>>I'M BLOWN AWAY BY THE

568
00:22:47,520 --> 00:22:49,080
INCREDIBLE EXPERTISE WE

569
00:22:49,080 --> 00:22:50,320
ASSEMBLED HERE. THANK YOU ALL,

570
00:22:50,320 --> 00:22:51,600
REALLY EXCITED TO HAVE YOU

571
00:22:51,600 --> 00:22:54,600
JOINING US. T BEFORE WE BEGIN

572
00:22:54,600 --> 00:22:55,600
OUR SUBSTANTIVE DISCUSSION I

573
00:22:55,600 --> 00:22:56,880
WOULD LIKE TO PROVIDE CONTEXT

574
00:22:56,880 --> 00:22:59,640
FOR THE ROUND TABLE. AS YOU KNOW

575
00:22:59,640 --> 00:23:01,200
KNEE OSTEOARTHRITIS IS A

576
00:23:01,200 --> 00:23:01,760
DEGENERATIVE CONDITION

577
00:23:01,760 --> 00:23:03,240
CHARACTERIZED BY WEARING AWAY OF

578
00:23:03,240 --> 00:23:06,360
CARTILAGE IN THE KNEE. AND THIS

579
00:23:06,360 --> 00:23:07,320
GRADUAL WE ARE AND TEAR

580
00:23:07,320 --> 00:23:08,200
PROGRESSION OF KNEE

581
00:23:08,200 --> 00:23:09,160
OSTEOARTHRITIS LEADS TO

582
00:23:09,160 --> 00:23:11,440
DEVELOPMENT OF BONE SPURS AND

583
00:23:11,440 --> 00:23:12,880
WORSENING PAIN. THUS, IT IS A

584
00:23:12,880 --> 00:23:14,560
VERY IMPORTANT AREA FOCUS FOR

585
00:23:14,560 --> 00:23:16,200
NIAMS AND FOR OUR PUBLIC HEALTH

586
00:23:16,200 --> 00:23:19,480
MISSION. REGENERATIVE MEDICINE

587
00:23:19,480 --> 00:23:21,840
HAS BROUGHT HEALTH APPLICATIONS

588
00:23:21,840 --> 00:23:23,080
IN KNEE OSTEOARTHRITIS, USED FOR

589
00:23:23,080 --> 00:23:26,160
DEVELOPING METHODS TO REGROW,

590
00:23:26,160 --> 00:23:28,560
REPAIR OR REPLACE DAMAGED

591
00:23:28,560 --> 00:23:30,360
CARTILAGE. SO THE GOAL OF THIS

592
00:23:30,360 --> 00:23:31,600
PARTICULAR MEETING IS TO DISCUSS

593
00:23:31,600 --> 00:23:34,760
THE CHALLENGES, THE GAPS AND THE

594
00:23:34,760 --> 00:23:36,320
OPPORTUNITIES FACING THE FIELDS

595
00:23:36,320 --> 00:23:37,600
OF REGENERATIVE MEDS SIN AS

596
00:23:37,600 --> 00:23:39,040
RELATES TO CARTILAGE

597
00:23:39,040 --> 00:23:41,640
PRESERVATION AND RESTORATION IN

598
00:23:41,640 --> 00:23:44,200
KNEE OSTEOARTHRITIS. OVER THE

599
00:23:44,200 --> 00:23:45,520
LEONG TERM DISCUSSIONS OF THESE

600
00:23:45,520 --> 00:23:47,280
ROUND TABLES HAVE HELPED SHAPE

601
00:23:47,280 --> 00:23:48,160
THE INSTITUTE THINKING ABOUT

602
00:23:48,160 --> 00:23:52,000
AREAS TO PURSUE ACROSS OUR BASIC

603
00:23:52,000 --> 00:23:53,960
TRANSLATIONAL AND CLINICAL

604
00:23:53,960 --> 00:23:55,200
PORTFOLIOS. I'M PARTICULARLY

605
00:23:55,200 --> 00:23:56,640
INTERESTED IN LEARNING ABOUT

606
00:23:56,640 --> 00:23:57,760
WAYS WHICH NIAMS CAN FURTHER

607
00:23:57,760 --> 00:24:00,040
ENGAGE WITH RESEARCHERS TO

608
00:24:00,040 --> 00:24:01,480
SUPPORT THIS CRITICAL WORK AND

609
00:24:01,480 --> 00:24:02,800
CONTRIBUTE TO THE ADVANCEMENTED

610
00:24:02,800 --> 00:24:05,800
OF REGENERATIVE MEDICINE. NOW TO

611
00:24:05,800 --> 00:24:08,120
SET A FEW QUICK GROUND RULES. WE

612
00:24:08,120 --> 00:24:11,640
WANT TO LEARN FROM YOU, THE

613
00:24:11,640 --> 00:24:13,320
EXPERTS ABOUT THE BROAD

614
00:24:13,320 --> 00:24:14,560
LANDSCAPE OF REGENERATIVE

615
00:24:14,560 --> 00:24:16,560
MEDICINE AND IMPLICATIONS FOR

616
00:24:16,560 --> 00:24:17,440
KNEE OSTEOARTHRITIS. THUS WE

617
00:24:17,440 --> 00:24:18,560
DON'T WANT THE PRODUCTIVITY OF

618
00:24:18,560 --> 00:24:19,880
THIS ROUND TABLE TO BE LIMITED

619
00:24:19,880 --> 00:24:25,120
BY FOCUSING ON FUNDING AND

620
00:24:25,120 --> 00:24:26,240
DEVELOPMENT OF SPECIFIC FUNDING

621
00:24:26,240 --> 00:24:28,040
OPPORTUNITY ANNOUNCEMENT. NIAMS

622
00:24:28,040 --> 00:24:29,320
RECOGNIZES TODAY'S TOPIC

623
00:24:29,320 --> 00:24:30,960
PRESENTS MANY EXCITING AND

624
00:24:30,960 --> 00:24:32,520
INNOVATIVE OPPORTUNITIES FOR

625
00:24:32,520 --> 00:24:33,560
DISCOVERING AND WILL BE CALLING

626
00:24:33,560 --> 00:24:35,080
ON EACH OF YOU FOR YOUR INPUT

627
00:24:35,080 --> 00:24:36,520
OVER THE COURSE OF THE ROUND

628
00:24:36,520 --> 00:24:38,880
TABLE TO SHARE YOUR EXPERIENCES

629
00:24:38,880 --> 00:24:41,120
ABOUT CARTILAGE PRESERVATION AND

630
00:24:41,120 --> 00:24:44,680
RESTORATION RESEARCH TODAY AS

631
00:24:44,680 --> 00:24:45,520
WELL AS FOO UTURE OPPORTUNITIES

632
00:24:45,520 --> 00:24:47,160
AS YOU SEE THEM. WE WILL ALSO

633
00:24:47,160 --> 00:24:48,840
POST SUMMARY OF TODAY'S

634
00:24:48,840 --> 00:24:50,280
DELIBERATIONS ALEONG WITH LINK

635
00:24:50,280 --> 00:24:52,400
TO RECORDING THE VIDEOCAST ON

636
00:24:52,400 --> 00:24:54,040
THE NIAMS WEBSITE. WE WILL LET

637
00:24:54,040 --> 00:24:55,160
YOU KNOW WHEN SUMMARY IS

638
00:24:55,160 --> 00:24:57,680
AVAILABLE AND ENCOURAGE YOU TO

639
00:24:57,680 --> 00:24:59,920
SHARE WITH THOSE CANVAS FOR

640
00:24:59,920 --> 00:25:01,600
INPUT IN ADVANCE OF THE MEETING.

641
00:25:01,600 --> 00:25:02,960
SOME FINAL QUICK REMINDERS

642
00:25:02,960 --> 00:25:06,800
BEFORE I TURN THINGS TO OUR

643
00:25:06,800 --> 00:25:09,920
CHAIR, DR. DRUGAN. SHE HAS A FEW

644
00:25:09,920 --> 00:25:13,480
THINGS TO SHARE ABOUT LOGISTICS.

645
00:25:13,480 --> 00:25:13,760
JONELLE.

646
00:25:13,760 --> 00:25:15,520
>>THANK YOU, DR.
CRISWELL. A

647
00:25:15,520 --> 00:25:18,000
QUICK REMINDER THIS MEETING IS

648
00:25:18,000 --> 00:25:19,680
VIDEOCAST AND I JUST LEARNED

649
00:25:19,680 --> 00:25:22,360
FROM SOME OF MY COLLEAGUES WE

650
00:25:22,360 --> 00:25:25,320
HAVE 70 VIEWERS SO FAR. AND THAT

651
00:25:25,320 --> 00:25:28,120
NUMBER WILL ONLY GROW BASED ON

652
00:25:28,120 --> 00:25:29,440
EXPERIENCE THAT PEOPLE WILL TUNE

653
00:25:29,440 --> 00:25:31,560
IN THROUGH THE DAY, PROMISE

654
00:25:31,560 --> 00:25:32,640
THESE 70 OSTEOARTHRITIS ARE NOT

655
00:25:32,640 --> 00:25:33,960
ALL MY FRIENDS AND FAMILY SO

656
00:25:33,960 --> 00:25:36,200
THERE'S CLEARLY PEOPLE OUT THERE

657
00:25:36,200 --> 00:25:39,560
WHO ARE IN SCIENTIFIC COMMUNITY

658
00:25:39,560 --> 00:25:40,320
WHO ARE INTERESTED IN WHAT WE

659
00:25:40,320 --> 00:25:42,040
ARE TALKING ABOUT TODAY.  WE ASK

660
00:25:42,040 --> 00:25:43,360
OUR INVITED PARTICIPANTS TO

661
00:25:43,360 --> 00:25:44,920
PLEASE KEEP YOUR VIDEO ON FOR

662
00:25:44,920 --> 00:25:49,960
THE DISCUSSION PORTION OF THE

663
00:25:49,960 --> 00:25:51,440
MEETING TO HELP DISCUSSION

664
00:25:51,440 --> 00:25:52,480
CO-CHAIRS TO KNOW WHO IS ON

665
00:25:52,480 --> 00:25:53,880
DURING THE DISCUSSION.  STAFF

666
00:25:53,880 --> 00:25:55,560
KEEP YOUR CAMERAS OFF P UNLESS

667
00:25:55,560 --> 00:25:57,040
YOU ARE SPEAKING AND IF YOU ARE

668
00:25:57,040 --> 00:26:01,200
SPEAKING INTRODUCE YOURSELF

669
00:26:01,200 --> 00:26:02,760
SINCE YOU WERE NOT INTRODUCE

670
00:26:02,760 --> 00:26:05,600
WHEN DID DID AS ROLL CALL. TO

671
00:26:05,600 --> 00:26:06,640
EVERYONE, PLEASE MUTE YOUR

672
00:26:06,640 --> 00:26:08,920
MICROPHONE UNLESS SPEAKING. IF

673
00:26:08,920 --> 00:26:10,880
YOU WOULD LIKE TO SPEAK DURING

674
00:26:10,880 --> 00:26:12,040
THE DISCUSSION RAISE YOUR HAND

675
00:26:12,040 --> 00:26:13,200
BY CLICKING ON THE PARTICIPANT

676
00:26:13,200 --> 00:26:15,400
ICON AT THE BOTTOM OF THE

677
00:26:15,400 --> 00:26:17,280
SCREEN. AT THE BOTTOM OF THE

678
00:26:17,280 --> 00:26:18,440
PARTICIPANT WINDOW YOU WILL SEE

679
00:26:18,440 --> 00:26:20,640
AN OPTION TO RAISE YOUR HAND. 

680
00:26:20,640 --> 00:26:23,600
THE CO-CHAIR WILL CALL ON YOU TO

681
00:26:23,600 --> 00:26:25,720
SPEAK, NIAMS PROGRAM STAFF AND

682
00:26:25,720 --> 00:26:28,920
TED MAINLY WILL LOOK FOR

683
00:26:28,920 --> 00:26:30,360
CO-CHAIRS TO LOOK FOR RAISED

684
00:26:30,360 --> 00:26:32,480
HANDS AND HE WILL MONITOR THE

685
00:26:32,480 --> 00:26:33,600
CHAT FOR COMMENTS. WE HAVE JUST

686
00:26:33,600 --> 00:26:35,480
LEARNED FROM EXPERIENCE THAT WE

687
00:26:35,480 --> 00:26:36,800
PREFER FOR YOU TO MAKE YOUR

688
00:26:36,800 --> 00:26:38,720
COMMENTS VERBALLY BECAUSE THAT

689
00:26:38,720 --> 00:26:40,720
LEADS TO A MORE ROBUST

690
00:26:40,720 --> 00:26:41,840
DISCUSSION. PLEASE REMEMBER TO

691
00:26:41,840 --> 00:26:44,920
LOWER YOUR HANDS WHILE SPEAKING.

692
00:26:44,920 --> 00:26:47,240
DAVE IS GOING TO BE DOING TIME

693
00:26:47,240 --> 00:26:49,200
KEEPING. I'M RUSHING THROUGH

694
00:26:49,200 --> 00:26:52,920
THESE REMARKS SO WE CAN STAY ON

695
00:26:52,920 --> 00:26:55,720
TIME. ONE OTHER THING YOU WILL

696
00:26:55,720 --> 00:26:57,360
SEE ON THE AGENDA WE HAVE A

697
00:26:57,360 --> 00:26:59,280
PHOTO FOR A GROUP LUNCH, COUPLE

698
00:26:59,280 --> 00:27:00,320
OF PEOPLE ASKED ABOUT THAT, IT

699
00:27:00,320 --> 00:27:04,920
IS NOT A TYPO. WE WILL TAKE A

700
00:27:04,920 --> 00:27:06,400
SCREEN SHOT OF OUR GROUP. IT IS

701
00:27:06,400 --> 00:27:08,800
A TRADITION AS WE HAVE TAKEN

702
00:27:08,800 --> 00:27:10,800
PHOTOS AT ALMOST EVERY NIAMS

703
00:27:10,800 --> 00:27:12,040
ROUND TABLE AND THIS IS

704
00:27:12,040 --> 00:27:13,160
SOMETHING WE DIDN'T WANT TO GIVE

705
00:27:13,160 --> 00:27:15,920
UP DURING THIS PERIOD OF VIRTUAL

706
00:27:15,920 --> 00:27:19,040
MEETINGS. DR. CRISWELL, GIVE YOU

707
00:27:19,040 --> 00:27:20,880
AN OPPORTUNITY TO TAKE QUESTIONS

708
00:27:20,880 --> 00:27:21,880
BEFORE TURNING THE MEETING OVER

709
00:27:21,880 --> 00:27:25,080
TO OUR CO-CHAIRS.  THANK YOU. 

710
00:27:25,080 --> 00:27:26,240
>>THANK YOU FOR YOUR

711
00:27:26,240 --> 00:27:26,920
PARTICIPATION, LOOKING FORWARD

712
00:27:26,920 --> 00:27:29,120
TO A PRODUCTIVE DISCUSSION.

713
00:27:29,120 --> 00:27:30,760
BEFORE WE BEGIN, ARE THERE ANY

714
00:27:30,760 --> 00:27:41,000
QUESTIONS?

715
00:27:49,920 --> 00:27:52,480
>>HEARING UP IN I WILL
TURN IT

716
00:27:52,480 --> 00:27:53,960
TO DR. ZHENG.

717
00:27:53,960 --> 00:27:57,680
>>WE WILL STAR START. DR.
ROAD,

718
00:27:57,680 --> 00:27:58,640
DR. CHU, YOU ARE ON.

719
00:27:58,640 --> 00:28:04,480
>>THANK YOU, EVERYBODY.
IT

720
00:28:04,480 --> 00:28:05,480
GIVES ME GREAT PLEASURE TO

721
00:28:05,480 --> 00:28:08,720
INTRODUCE THE FIRST SPEAKER. SO

722
00:28:08,720 --> 00:28:09,920
AMYE LEONG WILL TALK TO US ABOUT

723
00:28:09,920 --> 00:28:14,200
THE PATIENT PERSPECTIVE. I WANT

724
00:28:14,200 --> 00:28:17,280
TO HIGHLIGHT MORE ABOUT HER

725
00:28:17,280 --> 00:28:20,640
BACKGROUND. SO SHE WAS 18 YEARS

726
00:28:20,640 --> 00:28:24,560
OLD WHEN SHE RECEIVED THE

727
00:28:24,560 --> 00:28:25,920
DIAGNOSIS OF RHEUMATOID

728
00:28:25,920 --> 00:28:33,160
ARTHRITIS.  THIS WAS FOLLOWED BY

729
00:28:33,160 --> 00:28:35,720
OSTEOPOROSIS DIAGNOSIS.  SHE WAS

730
00:28:35,720 --> 00:28:37,560
WHEELCHAIR BOUND IN SIX YEARS

731
00:28:37,560 --> 00:28:39,880
AND SHE SPENT FIVE YEARS IN A

732
00:28:39,880 --> 00:28:43,760
WHEELCHAIR. SHE HAD MORE THAN 22

733
00:28:43,760 --> 00:28:45,400
SURGERIES AND 20 JOINT

734
00:28:45,400 --> 00:28:46,360
REPLACEMENTS OVER THE SUBSEQUENT

735
00:28:46,360 --> 00:28:51,720
YEARS. DURING THIS TIME SHE

736
00:28:51,720 --> 00:28:53,400
DEVELOPED AMERICA'S LARGEST

737
00:28:53,400 --> 00:28:55,720
NETWORK OF YOUNG ADULT EDUCATION

738
00:28:55,720 --> 00:28:56,960
AND ADVOCACY PROGRAMS. SHE

739
00:28:56,960 --> 00:28:59,080
STARTED A CONSULTING FIRM AND

740
00:28:59,080 --> 00:29:01,600
DECIDED THAT SHE WAS GOING TO

741
00:29:01,600 --> 00:29:06,640
GET OFF OF DISABILITY AND SHE

742
00:29:06,640 --> 00:29:10,720
HAS REALLY BROUGHT THE PATIENT

743
00:29:10,720 --> 00:29:14,360
PERSPECTIVE TO BARE OVER NUMBER

744
00:29:14,360 --> 00:29:15,800
OF YEARS WORKING WITH NOT JUST

745
00:29:15,800 --> 00:29:21,600
NIAMS BUT PCORI AHRQ, AND IS

746
00:29:21,600 --> 00:29:24,440
RECOGNIZED BY PRESIDENT BUSH FOR

747
00:29:24,440 --> 00:29:27,040
HER CONTRIBUTIONS, SO WE ARE

748
00:29:27,040 --> 00:29:29,160
REALLY THRILLED THAT SHE IS ABLE

749
00:29:29,160 --> 00:29:31,720
TO KICK OFF OUR MEETING. PLEASE

750
00:29:31,720 --> 00:29:36,720
JOIN ME TO WELCOME AMYE LEONG.

751
00:29:36,720 --> 00:29:40,800
>>THANK YOU, DR. CHU. I
AM

752
00:29:40,800 --> 00:29:42,320
DELIGHTED TO BE HERE FIRST OF

753
00:29:42,320 --> 00:29:45,000
ALL, THANK YOU SO MUCH, DR.

754
00:29:45,000 --> 00:29:53,080
CRISWELL AND GREAT, GREAT NIAMS

755
00:29:53,080 --> 00:29:55,280
TEAM. AS SOMEONE PREVIOUSLY

756
00:29:55,280 --> 00:29:59,240
SAID, THEY GREW UP IN NIAMS. AND

757
00:29:59,240 --> 00:30:03,440
I AM ONE OF THOSE PEOPLE NOT WHO

758
00:30:03,440 --> 00:30:04,680
GREW UP WITHIN THE SYSTEM BUT

759
00:30:04,680 --> 00:30:09,840
GREW UP ALONGSIDE THE SYSTEM.

760
00:30:09,840 --> 00:30:11,720
WHO ASKED TO JUMP THE RIVER AND

761
00:30:11,720 --> 00:30:14,240
COME OVER ON OCCASIONAL BASIS.

762
00:30:14,240 --> 00:30:15,840
MY INVOLVEMENT STARTED WITH ARE

763
00:30:15,840 --> 00:30:17,240
YOU SURE YOU WANT TO INVITE A

764
00:30:17,240 --> 00:30:18,240
PATIENT TO THIS RESEARCH ROUND

765
00:30:18,240 --> 00:30:22,800
TABLE? TO WHY DON'T WE INVITE

766
00:30:22,800 --> 00:30:24,720
PATIENTS IN AN OPPORTUNITY TO

767
00:30:24,720 --> 00:30:27,000
BRING ALL STAKEHOLDERS TOGETHER.

768
00:30:27,000 --> 00:30:30,360
YOU CAN SEE THE TRAJECTORY.

769
00:30:30,360 --> 00:30:32,000
TODAY WE AND THE FIELD OF

770
00:30:32,000 --> 00:30:36,200
MEDICINE IF YOU WILL, IN THE

771
00:30:36,200 --> 00:30:37,760
FIELD OF STRUCTURAL MEDICINE,

772
00:30:37,760 --> 00:30:39,720
CALL THIS PATIENT ENGAGEMENT.

773
00:30:39,720 --> 00:30:41,720
I'M SO EXCITED TO HAVE BEEN A

774
00:30:41,720 --> 00:30:43,080
PART OF THIS IN THE VERY

775
00:30:43,080 --> 00:30:44,520
BEGINNING. THOUGH WE DIDN'T KNOW

776
00:30:44,520 --> 00:30:47,800
WHAT NAME IT WAS. SO THE KINDS

777
00:30:47,800 --> 00:30:48,840
OF THINGS WE WILL TALK ABOUT IN

778
00:30:48,840 --> 00:30:50,960
THE VERY BRIEF TIME I HAVE WITH

779
00:30:50,960 --> 00:30:53,920
YOU AND SOMETIMES I WILL SPEAK

780
00:30:53,920 --> 00:30:58,880
VERY FAST, I ASK YOU TO BEAR

781
00:30:58,880 --> 00:31:02,040
WITH ME, 30 YEARS AGO A LOT OF

782
00:31:02,040 --> 00:31:05,680
THESE ORGANIZATIONS DID NOT

783
00:31:05,680 --> 00:31:07,440
EXIST. HOWEVER BECAUSE OF THESE

784
00:31:07,440 --> 00:31:08,280
ORGANIZATIONS OBVIOUSLY THE

785
00:31:08,280 --> 00:31:10,440
NATIONAL INSTITUTE OF ARTHRITIS

786
00:31:10,440 --> 00:31:12,080
MUSCULOSKELETAL AND SKIN

787
00:31:12,080 --> 00:31:13,520
DISEASES, THE NIH DIRECTORS

788
00:31:13,520 --> 00:31:17,040
OFFICE, ABSOLUTELY. U.S. BONE

789
00:31:17,040 --> 00:31:19,280
AND JOINT DECADE, ABSOLUTELY. AT

790
00:31:19,280 --> 00:31:22,080
THE GLOBAL LEVEL I HAVE SERVED

791
00:31:22,080 --> 00:31:23,800
FOR 15 YEARS AS THEIR

792
00:31:23,800 --> 00:31:25,800
INTERNATIONAL SPOKESPERSON. THE

793
00:31:25,800 --> 00:31:27,440
ARTHRITIS FOUNDATION HERE IN THE

794
00:31:27,440 --> 00:31:31,440
UNITED STATES BECAME MY HOME

795
00:31:31,440 --> 00:31:35,480
BASE. I WANT TO THANK DR. JASON

796
00:31:35,480 --> 00:31:36,640
KIM FOR HELPING THE SLIDES,

797
00:31:36,640 --> 00:31:38,160
BECAUSE IT IS NOT JUST MY

798
00:31:38,160 --> 00:31:39,400
PERSPECTIVE, IT IS A PERSPECTIVE

799
00:31:39,400 --> 00:31:44,360
THAT WE ARE SEEING IN THE PUBLIC

800
00:31:44,360 --> 00:31:47,320
HEARING FROM THE PUBLIC AND WANT

801
00:31:47,320 --> 00:31:48,560
TO SHARE THAT WITH YOU A GREAT

802
00:31:48,560 --> 00:31:51,640
DEAL. THE GLOBAL ALLIANCE FOR

803
00:31:51,640 --> 00:31:53,080
MUSCULOSKELETAL HEALTH, NAMES,

804
00:31:53,080 --> 00:31:59,160
NIH, PCORI AND THE FDA

805
00:31:59,160 --> 00:32:00,680
A. CXFC DISCROW SURE I SERVE AS

806
00:32:00,680 --> 00:32:02,560
FOUNDING MEMBER OF PATIENT --

807
00:32:02,560 --> 00:32:04,600
DISCLOSURE I SERVE AS PATIENT

808
00:32:04,600 --> 00:32:05,840
ENGAGEMENT ADVISORY COMMITTEE

809
00:32:05,840 --> 00:32:08,800
OUT OF CDRH AT THE FDA. SO

810
00:32:08,800 --> 00:32:10,600
ANOTHER GREAT HOME FOR AND

811
00:32:10,600 --> 00:32:13,160
OPPORTUNITY FOR PATIENTS TO

812
00:32:13,160 --> 00:32:19,520
ENGAGE. NEXT SLIDE. SO VERY

813
00:32:19,520 --> 00:32:20,440
QUICK VISION STATEMENT OF THE

814
00:32:20,440 --> 00:32:23,320
ARTHRITIS FOUNDATION, IN TERMS

815
00:32:23,320 --> 00:32:25,640
OF SCIENCE, BUT DON'T LOOK AT IT

816
00:32:25,640 --> 00:32:27,760
AS JUST THAT OWNED BY THE AF, IT

817
00:32:27,760 --> 00:32:30,880
IS A STATEMENT THAT ACTUALLY

818
00:32:30,880 --> 00:32:32,720
BINDS US ALL TOGETHER TO RELIEVE

819
00:32:32,720 --> 00:32:37,240
THE BURDENS OF OSTEOARTHRITIS

820
00:32:37,240 --> 00:32:38,480
PATIENTS THROUGH SCIENCE.

821
00:32:38,480 --> 00:32:40,680
CRITICAL PIECE. IN THIS DAY AND

822
00:32:40,680 --> 00:32:44,440
AGE, LET ME GO ON, IN THIS DAY

823
00:32:44,440 --> 00:32:46,320
AND AGE, GIVING IDEA THE

824
00:32:46,320 --> 00:32:48,320
ARTHRITIS FOUNDATION IS CON VIE

825
00:32:48,320 --> 00:32:51,000
NOR IN IMPORTANT MEET --

826
00:32:51,000 --> 00:32:53,600
CONVENER IN IMPORTANT MEETINGS.

827
00:32:53,600 --> 00:32:56,080
YOU CAN SEE OUR FDA PERSON

828
00:32:56,080 --> 00:32:58,600
THERE, MARK HOPBURG IS

829
00:32:58,600 --> 00:32:59,840
REPRESENTED, MANY OF YOU IN THE

830
00:32:59,840 --> 00:33:01,960
AUDIENCE NOW HAVE PARTICIPATED.

831
00:33:01,960 --> 00:33:08,960
MOVING ONWARD.  YOU CAN SEE THAT

832
00:33:08,960 --> 00:33:12,800
DR. RODEO, DR. BROADER, MANY

833
00:33:12,800 --> 00:33:16,400
OTHERS HAVE BEEN PART OF THIS.

834
00:33:16,400 --> 00:33:19,200
DR. MUSCHLER ALSO VERY MUCH

835
00:33:19,200 --> 00:33:21,000
LEADERS IN THIS AREA. SO IT IS

836
00:33:21,000 --> 00:33:22,680
NOT JUST ARTHRITIS FOUNDATION

837
00:33:22,680 --> 00:33:25,600
THING, BUT IT IS AN OPPORTUNITY

838
00:33:25,600 --> 00:33:28,360
THROUGH OTHER CONNECTED ENTITIES

839
00:33:28,360 --> 00:33:30,600
TO BEGIN TO WORK TOGETHER TO

840
00:33:30,600 --> 00:33:31,880
SHARE THE WEALTH TO MOVE FORWARD

841
00:33:31,880 --> 00:33:40,560
TOGETHER. I WANT TO ADDRESS FEW

842
00:33:40,560 --> 00:33:43,000
PUBLIC MISCONCEPTIONS, THE LIST

843
00:33:43,000 --> 00:33:44,440
IS TEN TIMES BIGGER THAN THIS

844
00:33:44,440 --> 00:33:45,480
BUT CERTAINLY AS YOU GO THROUGH

845
00:33:45,480 --> 00:33:47,040
AND READ IT YOU CAN COME BACK TO

846
00:33:47,040 --> 00:33:51,480
THE SLIDE AT YOUR OWN WILL BUT

847
00:33:51,480 --> 00:33:52,800
THERE IS A LOT OF

848
00:33:52,800 --> 00:33:56,120
MISCONCEPTIONS. THE FIRST THING

849
00:33:56,120 --> 00:33:58,840
IS THE FIRST IS EVERYBODY SAYS

850
00:33:58,840 --> 00:34:01,400
IT, NOTHING CAN BE DONE. FOR MY

851
00:34:01,400 --> 00:34:06,400
OA AND MY OA ARM OR KNEE OR OA

852
00:34:06,400 --> 00:34:08,080
ELBOW. WHATEVER THAT BODY PART

853
00:34:08,080 --> 00:34:10,760
IS, AND I KNOW FOCUS IS ON

854
00:34:10,760 --> 00:34:13,560
CARTILAGE TODAY, THE KNEE IN

855
00:34:13,560 --> 00:34:14,400
PARTICULAR BUT THE WIDER

856
00:34:14,400 --> 00:34:19,000
PERCEPTION OF THE PUBLIC IS THAT

857
00:34:19,000 --> 00:34:20,840
WHEN THERE IS A PERCEPTION OF A

858
00:34:20,840 --> 00:34:22,000
HITCH IN THE GET ALEONG, THAT'S

859
00:34:22,000 --> 00:34:25,360
A COLLOQUIAL WAY OF SAYING ITS

860
00:34:25,360 --> 00:34:27,160
HURTS, I CAN'T FUNCTION WIT, I

861
00:34:27,160 --> 00:34:28,280
CAN'T DO WHAT I NORMALLY DO WITH

862
00:34:28,280 --> 00:34:38,840
IT. WHAT HELP CAN I GET? IF YOU

863
00:34:42,400 --> 00:34:43,360
HAVE DONE A SEARCH ON THE

864
00:34:43,360 --> 00:34:46,400
INTERNET YOU SEE THE PUBLIC

865
00:34:46,400 --> 00:34:48,840
MISCONCEPTIONS ARE RAMPANT.

866
00:34:48,840 --> 00:34:50,000
THEREFORE IS THAT RIGHT TANS,

867
00:34:50,000 --> 00:34:51,800
UNPROVEN REMEDIES THOSE KINDS OF

868
00:34:51,800 --> 00:34:55,120
THINGS OCCUR. BUT THERE IS HIGH

869
00:34:55,120 --> 00:34:59,120
INTEREST. TO GET FROM THIS SLIDE

870
00:34:59,120 --> 00:35:01,080
IS THE LITTLE SQUIGGLY LINES

871
00:35:01,080 --> 00:35:02,280
THAT REPRESENT THE BLUE KNEE

872
00:35:02,280 --> 00:35:05,240
PAIN AND THE GREEN SHOULDER

873
00:35:05,240 --> 00:35:09,840
PAIN, THESE ARE THE KINDS OF

874
00:35:09,840 --> 00:35:10,600
SEARCH WEB SEARCH TRENDS THAT

875
00:35:10,600 --> 00:35:13,120
HAVE BEEN GOING ON AND PRODUCED

876
00:35:13,120 --> 00:35:14,960
BY GOOGLE FOR OUR REVIEW WHICH

877
00:35:14,960 --> 00:35:16,600
IS VERY INTERESTING SO THE TOP

878
00:35:16,600 --> 00:35:18,640
TWO IN TERMS OF WHERE PEOPLE ARE

879
00:35:18,640 --> 00:35:20,840
TRYING TO GO TO SEARCH ARE KNEE

880
00:35:20,840 --> 00:35:23,360
AND SHOULDER. BUT THERE IS A

881
00:35:23,360 --> 00:35:24,760
CLOSE ALIGNMENT WITH HIP AS

882
00:35:24,760 --> 00:35:26,920
WELL. SO THERE IS A LOT OF

883
00:35:26,920 --> 00:35:29,080
DESIRE OUT THERE. THESE ARE --

884
00:35:29,080 --> 00:35:35,280
THE NUMBERS ARE IN THE MILLIONS 

885
00:35:35,280 --> 00:35:39,080
HERE IS ANOTHER THAT SAYS NOT

886
00:35:39,080 --> 00:35:41,560
JUST ABOUT THE KNEE, IT IS

887
00:35:41,560 --> 00:35:42,960
BEYONDS THE KNEE, THE KNEE IS

888
00:35:42,960 --> 00:35:46,240
THE MOST RESEARCHED JOINT IN OA

889
00:35:46,240 --> 00:35:47,760
BUT NOT ALL PATIENTS ARE

890
00:35:47,760 --> 00:35:51,120
AFFECTED IN KNEE AS YOU KNOW. 

891
00:35:51,120 --> 00:35:52,360
TOTAL JOINT REPLACEMENTS ARE A

892
00:35:52,360 --> 00:35:54,000
GOOD OPTION BUT AS DR. CRISWELL

893
00:35:54,000 --> 00:35:57,000
SAID WE CAN'T KEEP DOING THIS.

894
00:35:57,000 --> 00:35:58,360
THERE ARE TOO MANY PEOPLE

895
00:35:58,360 --> 00:36:01,080
GETTING THEM. HI MYSELF AM OWNER

896
00:36:01,080 --> 00:36:06,960
OF 20. SUCCESSFULLY OVER THE

897
00:36:06,960 --> 00:36:07,760
PAST LAST YOU WERE TEEN YEARS

898
00:36:07,760 --> 00:36:09,440
BUT NEWEST IS NOT DOING SO WELL.

899
00:36:09,440 --> 00:36:16,160
AND ALSO LOOKING AT KNEE OA AND

900
00:36:16,160 --> 00:36:17,840
HIP OA, IN THE MILLIONS HIGHER

901
00:36:17,840 --> 00:36:22,320
UP IN TERMS OF WHAT PEOPLE ARE

902
00:36:22,320 --> 00:36:23,560
SEEKING, WHAT THEY WANT TO DO

903
00:36:23,560 --> 00:36:28,400
ABOUT IT, THEN WHEN YOU LOOK AT

904
00:36:28,400 --> 00:36:30,240
THIS IS NUMBER OF PUBMED RESULTS

905
00:36:30,240 --> 00:36:30,920
THAT OSTEOARTHRITIS AND

906
00:36:30,920 --> 00:36:32,840
RHEUMATOID ARTHRITIS ARE THE

907
00:36:32,840 --> 00:36:37,440
LOWEST WHEN COMPARED TO

908
00:36:37,440 --> 00:36:44,760
ALZHEIMER'S DIABETES AND CANCER 

909
00:36:44,760 --> 00:36:46,600
LOT OF INTEREST BY PATIENTS BUT

910
00:36:46,600 --> 00:36:47,280
THE DIVERSITY PIECE IS

911
00:36:47,280 --> 00:36:48,920
INTERESTING. SO THE KNEE OA,

912
00:36:48,920 --> 00:36:53,440
THERE IS AGAIN HIGH, HIGH

913
00:36:53,440 --> 00:36:54,640
INTEREST THERE IS MORE INTEREST

914
00:36:54,640 --> 00:36:55,920
WHEN COMPARED IN OTHER DISEASE

915
00:36:55,920 --> 00:37:01,720
SPECIFIC AREAS, CANCER DIABETES,

916
00:37:01,720 --> 00:37:03,880
ALZHEIMERS HIGH INTEREST AREAS.

917
00:37:03,880 --> 00:37:05,640
BUT RHEUMATOID ARTHRITIS AND

918
00:37:05,640 --> 00:37:07,280
OSTEOARTHRITIS ARE VERY, VERY

919
00:37:07,280 --> 00:37:08,680
LITTLE. THIS IS FACTORED IN THE

920
00:37:08,680 --> 00:37:14,640
MILLIONS.  I PUT THIS RESEARCH

921
00:37:14,640 --> 00:37:19,080
STUDY UP ABOUT DIVERSITY LOOKING

922
00:37:19,080 --> 00:37:20,960
AT OA IN CHINA FOR THE FIRST

923
00:37:20,960 --> 00:37:25,920
TIME. WHAT THEY FOUND WAS

924
00:37:25,920 --> 00:37:28,160
CHINESE MEN FROM CHINA ACTUALLY

925
00:37:28,160 --> 00:37:33,560
HAD AN 80 TO 90% LESS INCIDENCE

926
00:37:33,560 --> 00:37:38,080
OF OA THAN MEN. IN THE UNITED

927
00:37:38,080 --> 00:37:39,680
STATES. THE ARTICLE WAS QUICK TO

928
00:37:39,680 --> 00:37:40,640
SAY THERE WERE WHITE MEN IN THE

929
00:37:40,640 --> 00:37:43,680
UNITED STATES.  SO I THINK THAT

930
00:37:43,680 --> 00:37:46,040
IS A VERY INTERESTING POINT

931
00:37:46,040 --> 00:37:49,360
ABOUT DIVERSITY. I THINK IT WAS

932
00:37:49,360 --> 00:37:51,680
MAYO CLINIC, ONE CLINIC

933
00:37:51,680 --> 00:37:53,000
ANNOUNCED TODAY THAT THEY ARE

934
00:37:53,000 --> 00:37:57,520
STARTING TO APPEAR A DIFFERENCE

935
00:37:57,520 --> 00:38:00,080
BETWEEN RACIAL CONFIGURATIONS IN

936
00:38:00,080 --> 00:38:03,800
SOME OF THE EARLY WORK. SO THOSE

937
00:38:03,800 --> 00:38:07,200
ARE KINDS OF THINGS WE NEED AND

938
00:38:07,200 --> 00:38:11,760
WANT AS PATIENTS TO CONSIDER. 

939
00:38:11,760 --> 00:38:13,600
SOMETHING THAT HELPS US FOR US

940
00:38:13,600 --> 00:38:19,800
BUT IS MORE LIKE US.  KNEE, VERY

941
00:38:19,800 --> 00:38:20,920
CLEARLY WE NEED MORE CLINICAL

942
00:38:20,920 --> 00:38:24,480
TRIALS. WE NEED MORE CHALLENGING

943
00:38:24,480 --> 00:38:26,280
RESEARCH QUESTIONS. I'M SO

944
00:38:26,280 --> 00:38:28,640
DELIGHTED TO BE PART OF NIAMS

945
00:38:28,640 --> 00:38:29,720
RESEARCH ROUNDS TABLES.  THIS IS

946
00:38:29,720 --> 00:38:31,040
THE TIME WHEN WE ARE ROLLING UP

947
00:38:31,040 --> 00:38:34,600
OUR SLEEVES AND SAYING HEY, HOW

948
00:38:34,600 --> 00:38:36,040
ABOUT IF I TALK TO YOU ABOUT

949
00:38:36,040 --> 00:38:37,920
THIS AND THIS, HOW ABOUT IF WE

950
00:38:37,920 --> 00:38:40,920
SIT DOWN AND MAP THIS THING OUT

951
00:38:40,920 --> 00:38:42,960
TOGETHER, IN WAYS YOU HAD NOT

952
00:38:42,960 --> 00:38:45,120
DONE BEFORE. SO THINKING OUTSIDE

953
00:38:45,120 --> 00:38:50,320
OF YOUR BOX. OUTSIDE YOUR

954
00:38:50,320 --> 00:38:52,040
INSTITUTION, YOUR DISTINCT AREAS

955
00:38:52,040 --> 00:38:54,920
OF SPECIALTY, BUT DOING WHAT I

956
00:38:54,920 --> 00:38:58,080
CALL THE JEFF BEZOS APPROACH.

957
00:38:58,080 --> 00:38:59,600
YOU BRING IN ALL THE APPROPRIATE

958
00:38:59,600 --> 00:39:01,960
PEOPLE YOU NEED TO BRING IN AND

959
00:39:01,960 --> 00:39:03,640
YOU SIT THEM DOWN AND YOU GIVE

960
00:39:03,640 --> 00:39:05,120
THEM ALL KINDS OF FOOD BUT YOU

961
00:39:05,120 --> 00:39:10,760
LOCK THE DOOR. YOU SAY PLEASE

962
00:39:10,760 --> 00:39:12,760
COME UP WITH IDEAS AND PRIORITY,

963
00:39:12,760 --> 00:39:19,560
LET'S MOVE IT FROM HERE.ED THE A

964
00:39:19,560 --> 00:39:21,800
FOUNDATION IS INTERESTED IN

965
00:39:21,800 --> 00:39:24,760
MOVING TO RESEARCH PHASE

966
00:39:24,760 --> 00:39:26,360
THEMSELVES. SO THE ARTHRITIS

967
00:39:26,360 --> 00:39:27,760
FOUNDATION MOST KNOW IS A

968
00:39:27,760 --> 00:39:30,040
PATIENT ADVOCACY PATIENT

969
00:39:30,040 --> 00:39:32,320
EDUCATION ORGANIZATION. HOWEVER,

970
00:39:32,320 --> 00:39:34,400
RECENTLY THEY ARE ANNOUNCING

971
00:39:34,400 --> 00:39:36,760
STILL ANNOUNCING TWO PARTICULAR

972
00:39:36,760 --> 00:39:41,400
THINGS, ONE THAT WAS ANNOUNCED

973
00:39:41,400 --> 00:39:43,840
YET AND ONE ANNOUNCED TWO MONTHS

974
00:39:43,840 --> 00:39:45,080
AGO. THE ONE ANNOUNCED TWO

975
00:39:45,080 --> 00:39:49,760
MONTHS AGO IS THE PIKASO

976
00:39:49,760 --> 00:39:54,000
PROJECT. SO THEY POOLED TOGETHER

977
00:39:54,000 --> 00:39:55,040
EIGHT INSTITUTIONS AND

978
00:39:55,040 --> 00:39:56,760
UNFORTUNATELY I CANNOT TELL YOU

979
00:39:56,760 --> 00:39:58,160
WHAT THEY ARE, OTHERWISE THEY

980
00:39:58,160 --> 00:40:00,840
WILL KILL ME BECAUSE IT IS

981
00:40:00,840 --> 00:40:02,200
PREMATURE, GETTING AN EARLY IN

982
00:40:02,200 --> 00:40:05,120
ON THIS. 50 PLUS WORLD CLASS

983
00:40:05,120 --> 00:40:07,880
SCIENTISTS, HUNDREDS OF PEOPLE

984
00:40:07,880 --> 00:40:12,720
WITH HIGH RISK OA AND TESTING

985
00:40:12,720 --> 00:40:14,240
EXCITING LOW COST DRUGS

986
00:40:14,240 --> 00:40:15,320
COMPARATIVE EFFECTIVENESS

987
00:40:15,320 --> 00:40:17,760
RESEARCH. SO THEY WILL BE

988
00:40:17,760 --> 00:40:18,960
EMBARKING ON THAT VENTURE

989
00:40:18,960 --> 00:40:22,560
STARTING IN 2023. THE MORE

990
00:40:22,560 --> 00:40:24,200
RECENT ONE WHICH WAS ANNOUNCED

991
00:40:24,200 --> 00:40:25,800
YESTERDAY, AT THE ANNUAL MEETING

992
00:40:25,800 --> 00:40:28,480
OF THE AMERICAN ORTHOPEDIC FOOT

993
00:40:28,480 --> 00:40:34,280
AND ANKLE SOCIETY IS A RESEARCH

994
00:40:34,280 --> 00:40:35,720
PARTNERSHIP WITH THE ARTHRITIS

995
00:40:35,720 --> 00:40:40,000
FOUNDATION AND AOFAS THAT WILL

996
00:40:40,000 --> 00:40:41,560
ESTABLISH SEVERAL MERITS. SO

997
00:40:41,560 --> 00:40:43,560
THIS IS WHAT IS HAPPENING, IT IS

998
00:40:43,560 --> 00:40:47,520
NOT GOING AWAY, THERE IS MORE OF

999
00:40:47,520 --> 00:40:50,920
IT.  I WANT TO LAST LEND ON THIS

1000
00:40:50,920 --> 00:40:52,160
IF YOU GIVE ME THREE MORE

1001
00:40:52,160 --> 00:40:53,800
MINUTES I APPRECIATE IT. THE

1002
00:40:53,800 --> 00:40:55,560
PICTURE ON THE RIGHT IS THE

1003
00:40:55,560 --> 00:40:58,000
LOWER HALF OF ME TODAY. YOU ARE

1004
00:40:58,000 --> 00:40:59,960
SEEING THE SHOULDERS AND UP PART

1005
00:40:59,960 --> 00:41:02,400
OF AMYE. THE SHOULDERS AND BELOW

1006
00:41:02,400 --> 00:41:05,240
IS WHAT YOU ARE SEEING ON THIS

1007
00:41:05,240 --> 00:41:09,720
PICTURE. MY LEG IS IN A FULL LEG

1008
00:41:09,720 --> 00:41:11,760
VERY BRIGHT PINK CAST. WHY?

1009
00:41:11,760 --> 00:41:14,800
BECAUSE I HAVE A TIBIA THAT DOES

1010
00:41:14,800 --> 00:41:16,720
NOT SUPPORT THE TOTAL KNEE JOINT

1011
00:41:16,720 --> 00:41:18,760
REPLACEMENT THAT WAS PUT IN. A

1012
00:41:18,760 --> 00:41:23,320
YEAR AND A HALF AGO. THIS IS A

1013
00:41:23,320 --> 00:41:24,920
NEW SCENARIO. IT IS ABOUT

1014
00:41:24,920 --> 00:41:26,560
QUALITY OF BONE. SO WHEN I THINK

1015
00:41:26,560 --> 00:41:30,000
ABOUT ANYTHING, I ALWAYS THINK

1016
00:41:30,000 --> 00:41:30,880
ABOUT QUALITY. QUALITY OF THE

1017
00:41:30,880 --> 00:41:33,000
FOOD, FRESHNESS OF THE FOOD,

1018
00:41:33,000 --> 00:41:36,120
QUALITY OF THE BONE THAT WILL BE

1019
00:41:36,120 --> 00:41:38,920
HOLDING A PROSTHESIS. AND HOW

1020
00:41:38,920 --> 00:41:41,320
LONG CANNA HAPPEN? HOW LONG CAN

1021
00:41:41,320 --> 00:41:43,840
I DO THAT? IN THE MEANTIME,

1022
00:41:43,840 --> 00:41:45,120
BEFORE WE CAN COME UP WITH A

1023
00:41:45,120 --> 00:41:47,400
SOLUTION WHICH IS THIS PICTURE

1024
00:41:47,400 --> 00:41:48,840
GETTING ME BACK INTO WHAT I USED

1025
00:41:48,840 --> 00:41:53,320
TO DO, YOGA, WALKING, THOSE

1026
00:41:53,320 --> 00:41:59,840
KINDS OF THINGS, IS A LONG HAUL 

1027
00:41:59,840 --> 00:42:03,320
SO PERSONALLY QUITE EFFECTIVELY

1028
00:42:03,320 --> 00:42:05,400
PATIENTS WANT ANSWERS NOW. NOT

1029
00:42:05,400 --> 00:42:07,160
TEN YEARS FROM NOW, NOT FIVE

1030
00:42:07,160 --> 00:42:09,240
YEARS FROM NOW. THEY WANT TO BE

1031
00:42:09,240 --> 00:42:10,000
ABLE TO HOLD THEIR BABY, THEY

1032
00:42:10,000 --> 00:42:11,720
WANT TO PICK UP THEIR BABY, PICK

1033
00:42:11,720 --> 00:42:14,120
UP THEIR CHILD, THEY WANT TO

1034
00:42:14,120 --> 00:42:17,880
WORK BECAUSE AS YOU KNOW,

1035
00:42:17,880 --> 00:42:21,160
DISABILITY FROM ARTHRITIS IS

1036
00:42:21,160 --> 00:42:24,920
AMONG THE TOP DISABLING

1037
00:42:24,920 --> 00:42:26,560
CONDITIONS IN THE UNITED STATES

1038
00:42:26,560 --> 00:42:28,440
AS WE KNOW TO BE COUNTING IT SO

1039
00:42:28,440 --> 00:42:30,880
THESE ARE BIG, BIG PROBLEMS. WE

1040
00:42:30,880 --> 00:42:33,000
NEED YOU, I NEED YOU. THAT IS

1041
00:42:33,000 --> 00:42:36,840
WHY I'M SO EXCITED TO BE HERE TO

1042
00:42:36,840 --> 00:42:39,280
BEGIN TO SEE MORE A BROADER

1043
00:42:39,280 --> 00:42:40,120
PERSPECTIVE ABOUT WHAT IT IS

1044
00:42:40,120 --> 00:42:43,040
THAT YOU DO, WHAT IT IS YOUR

1045
00:42:43,040 --> 00:42:45,720
EXPERTISE IS AND HOW WE CAN WORK

1046
00:42:45,720 --> 00:42:47,800
TOGETHER TO MOVE THIS ALONG

1047
00:42:47,800 --> 00:42:50,440
FASTER BETTER MORE EFFICIENTLY.

1048
00:42:50,440 --> 00:42:53,520
AND TO REALLY ADDRESS THE

1049
00:42:53,520 --> 00:42:57,200
PATIENTS' NEEDS. APPRECIATE YOUR

1050
00:42:57,200 --> 00:43:00,520
HELP. AS YOU CAN SEE THIS -- I

1051
00:43:00,520 --> 00:43:01,640
LIKE MOSAIC AND THAT IS WHAT I

1052
00:43:01,640 --> 00:43:03,320
WANT TO TALK ABOUT. I WANT YOU

1053
00:43:03,320 --> 00:43:05,000
TO ALWAYS THINK ABOUT THE BONES

1054
00:43:05,000 --> 00:43:06,800
AND CARTILAGE AND JOINTS WHAT

1055
00:43:06,800 --> 00:43:09,320
YOU TALK ABOUT AND WORKING ON

1056
00:43:09,320 --> 00:43:13,600
BUT TO ME IT IS HOW I FUNCTION.

1057
00:43:13,600 --> 00:43:18,640
THIS IS A BIG REQUEST. AND THE

1058
00:43:18,640 --> 00:43:20,640
REQUEST IS AS YOU GO BACK TO

1059
00:43:20,640 --> 00:43:23,040
YOUR RESEARCH LAB TO YOUR PETRI,

1060
00:43:23,040 --> 00:43:27,040
TO YOUR DESIGNS AND GENETIC

1061
00:43:27,040 --> 00:43:28,160
STUDIES THINK ABOUT EVERY ONE OF

1062
00:43:28,160 --> 00:43:32,400
THOSE CELLS REPRESENTING AMYE.

1063
00:43:32,400 --> 00:43:33,600
ME. ACTUALLY REPRESENTING ONES

1064
00:43:33,600 --> 00:43:36,000
YOU LOVE. THESE ARE REAL PEOPLE.

1065
00:43:36,000 --> 00:43:42,080
REAL LIVES.  THAT CAN BE HELPED

1066
00:43:42,080 --> 00:43:44,200
BY YOUR IDEAS AND YOUR

1067
00:43:44,200 --> 00:43:45,640
CONNECTEDNESS. I LOOK FORWARD TO

1068
00:43:45,640 --> 00:43:47,200
TODAY.  LET'S GO ABOUT IT AND DO

1069
00:43:47,200 --> 00:43:48,600
SOME GREAT STUFF. THANK YOU SO

1070
00:43:48,600 --> 00:43:55,640
MUCH.

1071
00:43:55,640 --> 00:43:59,320
>>THANK YOU SO MUCH FOR
THOSE

1072
00:43:59,320 --> 00:44:03,080
COMPELLING WORDS.

1073
00:44:03,080 --> 00:44:05,520
>>WHAT DO YOU SEE AS MOST

1074
00:44:05,520 --> 00:44:07,320
IMPORTANT BARRIERS TO PATIENTS

1075
00:44:07,320 --> 00:44:10,400
ENROLLING IN CLINICAL TRIALS?

1076
00:44:10,400 --> 00:44:12,760
>>ACTUALLY WORKING ON
THAT NOW,

1077
00:44:12,760 --> 00:44:17,880
PATIENT ENGAGEMENT. LACK OF

1078
00:44:17,880 --> 00:44:18,680
INFORMATION, KNOWLEDGE AND LACK

1079
00:44:18,680 --> 00:44:20,120
OF PEOPLE WHO LOOK LIKE

1080
00:44:20,120 --> 00:44:27,760
THEMSELVES, LEADING THE CHARGE. 

1081
00:44:27,760 --> 00:44:28,880
SOING THE IMPORTANT YOUR NAME IS

1082
00:44:28,880 --> 00:44:30,320
ON IT AND YOUR EXPERTISE IS

1083
00:44:30,320 --> 00:44:32,000
DRIVING IT BUT BEFORE YOU IS

1084
00:44:32,000 --> 00:44:35,320
SOMEBODY LIKE ME. DOESN'T HAVE

1085
00:44:35,320 --> 00:44:36,680
TO BE ME BUT LIKE ME WHO SAYS

1086
00:44:36,680 --> 00:44:37,960
THIS IS GOOD FOR ALL OF US. THIS

1087
00:44:37,960 --> 00:44:40,400
IS GOING TO ADVANCE. THE MORE

1088
00:44:40,400 --> 00:44:42,600
YOU ARE GIVING OF YOUR -- WHAT

1089
00:44:42,600 --> 00:44:44,160
YOU KNOW ABOUT THE DISEASE, WHAT

1090
00:44:44,160 --> 00:44:47,680
YOU KNOW ABOUT THE PAIN, WHAT

1091
00:44:47,680 --> 00:44:50,960
YOU KNOW IN TERMS OF FUNCTION.

1092
00:44:50,960 --> 00:44:53,040
THESE ARE IMPORTANT CONCEPTS. 

1093
00:44:53,040 --> 00:44:55,880
EXAMPLE, POST TRAUMATIC STRESS.

1094
00:44:55,880 --> 00:44:59,440
MANY OF YOU KNOW I LIVE IN SANTA

1095
00:44:59,440 --> 00:45:01,720
BARBARA, CALIFORNIA, I USED TO

1096
00:45:01,720 --> 00:45:05,080
LIVE IN MOTESETO AND OUR FAMILY

1097
00:45:05,080 --> 00:45:06,840
WAS AFFECTED BY THE FIRES AND

1098
00:45:06,840 --> 00:45:09,360
MUD SLIDES, WE LOST OUR HOUSE

1099
00:45:09,360 --> 00:45:10,720
AND ALMOST LOST OURSELVES IN ALL

1100
00:45:10,720 --> 00:45:16,720
OF THAT. IN THE BEGINNING OF

1101
00:45:16,720 --> 00:45:18,800
2018 AND IT HAS TAKEN US TWO

1102
00:45:18,800 --> 00:45:21,120
YEARS TO RECOVER JUST HAVING A

1103
00:45:21,120 --> 00:45:24,200
HOUSE. WE LOST EVERYTHING. I

1104
00:45:24,200 --> 00:45:26,520
LOST CHINA THAT GOES BACK FOUR

1105
00:45:26,520 --> 00:45:28,520
GENERATIONS IN MY FAMILY IN

1106
00:45:28,520 --> 00:45:31,480
CHINA. I LOST SO MANY WONDERFUL

1107
00:45:31,480 --> 00:45:33,040
PICTURES. BUT THE STRESS FROM

1108
00:45:33,040 --> 00:45:36,120
ALL THAT, NOT ONLY THE STRESS OF

1109
00:45:36,120 --> 00:45:38,920
THE TRAUMA BUT THE STRESS OF THE

1110
00:45:38,920 --> 00:45:43,080
BUILDING BACK PART HAS

1111
00:45:43,080 --> 00:45:44,720
INTRODUCED A WHOLE DIFFERENT

1112
00:45:44,720 --> 00:45:47,920
FOUNDATION FROM WHICH WHICH

1113
00:45:47,920 --> 00:45:49,920
IMMUNE SYSTEM NOW MORE CONGESTED

1114
00:45:49,920 --> 00:45:53,240
QUITE FRANKLY, TO TRY AND WORK

1115
00:45:53,240 --> 00:45:57,320
AND TO BE ON MY SIDE, THAT

1116
00:45:57,320 --> 00:46:01,080
HELPS.  HAS.  THANKS FOR THE QU.

1117
00:46:01,080 --> 00:46:04,040
>>AMYE, WE ALL WANT TO DO
THESE

1118
00:46:04,040 --> 00:46:05,560
CLINICAL TRIALS BECAUSE THAT IS

1119
00:46:05,560 --> 00:46:07,240
HOW WE WILL GET SOME ANSWERS BUT

1120
00:46:07,240 --> 00:46:08,760
I THINK MOST OF US FIND THE

1121
00:46:08,760 --> 00:46:12,400
BIGGEST OBSTACLE IS THE PATIENTS

1122
00:46:12,400 --> 00:46:14,480
DON'T WANT TO BE RANDOMIZE, THEY

1123
00:46:14,480 --> 00:46:16,560
HEAR THIS 50/50, MAYBE TRY TO

1124
00:46:16,560 --> 00:46:19,240
GET LESS THAN 50/50 FOR THE --

1125
00:46:19,240 --> 00:46:21,000
SO DO YOU HAVE ANY HINTS FOR US

1126
00:46:21,000 --> 00:46:23,160
THAT THAT IS WHAT I FIND MOST OF

1127
00:46:23,160 --> 00:46:25,800
US FIND IS BIGGEST OBSTACLE FOR

1128
00:46:25,800 --> 00:46:26,120
ADVANCING --

1129
00:46:26,120 --> 00:46:29,160
>>THAT IS A WEBINAR OF A
WHOLE

1130
00:46:29,160 --> 00:46:31,200
DIFFERENT NATURE. YES, THERE ARE

1131
00:46:31,200 --> 00:46:34,960
THINGS YOU CAN DO. T YOU HAVE TO

1132
00:46:34,960 --> 00:46:37,240
REMEMBER WE DO NOT HAVE YOUR

1133
00:46:37,240 --> 00:46:42,840
EDUCATIONAL BACKGROUND. WE DON'T

1134
00:46:42,840 --> 00:46:45,400
HAVE A SCIENCE MINDED APPROACH

1135
00:46:45,400 --> 00:46:49,480
TO DRAWING CONCLUSIONS. MUCH OF

1136
00:46:49,480 --> 00:46:51,560
THE PUBLIC I SAY IN A BROAD

1137
00:46:51,560 --> 00:46:54,320
FASHION, THERE IS A RANGE EVEN

1138
00:46:54,320 --> 00:46:57,080
IN THAT. ARE BASED ON YOUR

1139
00:46:57,080 --> 00:46:59,080
PERCEPTIONS. WHO YOU KNOW, WHAT

1140
00:46:59,080 --> 00:47:02,680
YOU KNOW, YOUR ACCESS EVEN DOWN

1141
00:47:02,680 --> 00:47:04,800
TO ETHNICITY OF HOW YOUR PARENTS

1142
00:47:04,800 --> 00:47:08,840
RAISE YOU IN TERMS OF PROBLEM

1143
00:47:08,840 --> 00:47:14,120
SOLVING. IS THERE A LOCAL

1144
00:47:14,120 --> 00:47:14,800
PATIENT GROUP ORGANIZATION

1145
00:47:14,800 --> 00:47:16,880
PREFERABLY, NOT JUST A GROUP

1146
00:47:16,880 --> 00:47:17,680
MEETING, AN ORGANIZATION THAT

1147
00:47:17,680 --> 00:47:19,360
CAN BE HELPFUL BUT THERE ARE

1148
00:47:19,360 --> 00:47:21,560
WAYS THAT CAN BE DONE. QUITE

1149
00:47:21,560 --> 00:47:23,880
HONESTLY, THE FACT IS, IN THE

1150
00:47:23,880 --> 00:47:27,520
THE RHEUMATOLOGY COMMUNITY, THAT

1151
00:47:27,520 --> 00:47:28,880
IS LARGER COMMUNITY RESEARCH

1152
00:47:28,880 --> 00:47:31,320
COMMUNITY, THAT WE BELONG TO,

1153
00:47:31,320 --> 00:47:32,640
THAT IS NOT REALLY AN ACTIVE

1154
00:47:32,640 --> 00:47:36,960
TOPIC. IT SHOULD BE. ABSOLUTELY

1155
00:47:36,960 --> 00:47:41,720
SHOULD BE. SO WE CAN BEGIN

1156
00:47:41,720 --> 00:47:42,800
PROCESS. IS THAT YOUR

1157
00:47:42,800 --> 00:47:44,400
RESPONSIBILITY? PROBABLY NOT BUT

1158
00:47:44,400 --> 00:47:46,280
I WILL TALK TO ARTHRITIS

1159
00:47:46,280 --> 00:47:49,240
FOUNDATION, I WILL TALK TO THE

1160
00:47:49,240 --> 00:47:52,120
ALLIANCE FOR GLOBAL

1161
00:47:52,120 --> 00:47:53,280
MUSCULOSKELETAL ACTION. I WILL

1162
00:47:53,280 --> 00:47:56,680
TALK TO A LOT -- PCORI DOES

1163
00:47:56,680 --> 00:47:57,600
DIFFERENT KINDS OF OPPORTUNITIES

1164
00:47:57,600 --> 00:48:03,000
THAT HELPS PEOPLE UNDERSTAND THE

1165
00:48:03,000 --> 00:48:04,000
SCIENTIFIC METHODOLOGY, THAT IS

1166
00:48:04,000 --> 00:48:04,520
REALLY IMPORTANT.

1167
00:48:04,520 --> 00:48:08,640
ONCE THEY UNDERSTAND THAT, OK O.

1168
00:48:08,640 --> 00:48:10,640
SO THEY MAY NOT LIKE IT, THEY

1169
00:48:10,640 --> 00:48:12,000
MAY NOT KNOW, THEY SHOULDN'T

1170
00:48:12,000 --> 00:48:15,000
EVEN KNOW BUT THE FACT IS YOU

1171
00:48:15,000 --> 00:48:18,480
HAVE TO TELL THEM A LITTLE BIT

1172
00:48:18,480 --> 00:48:21,640
BUT THEN SCOOT OVER IT.  BUT

1173
00:48:21,640 --> 00:48:22,840
THAT IS ANOTHER CONVERSATION SO

1174
00:48:22,840 --> 00:48:24,160
BE HAPPY TO ENTERTAIN THAT

1175
00:48:24,160 --> 00:48:26,880
LATER. 

1176
00:48:26,880 --> 00:48:31,120
>>I WILL TAKE THE MIC AS

1177
00:48:31,120 --> 00:48:32,240
PREROGATIVE TO STAY NEAR ON

1178
00:48:32,240 --> 00:48:35,120
TIME. MY PLEASURE TO INTRODUCE

1179
00:48:35,120 --> 00:48:36,160
CONNIE CHU WHO INTRODUCED

1180
00:48:36,160 --> 00:48:37,320
HERSELF EARLIER BUT BRIEFLY

1181
00:48:37,320 --> 00:48:40,360
PROFESSOR AND VICE CHAIR OF

1182
00:48:40,360 --> 00:48:43,160
RESEARCH AT STAN -- ALSO DIRECTS

1183
00:48:43,160 --> 00:48:44,200
THE JOINT PRESERVATION CENTER

1184
00:48:44,200 --> 00:48:46,720
AND CHIEF OF SPORTS MEDICINE AT

1185
00:48:46,720 --> 00:48:52,800
THE VA NEAR STANFO STANFORD.

1186
00:48:52,800 --> 00:48:54,160
ACCOMPLISHED SCIENTIST,

1187
00:48:54,160 --> 00:48:57,960
EXTENSIVE FUNDING, HER WORK IS

1188
00:48:57,960 --> 00:48:59,200
FOCUSED ON CARTILAGE REPAIR

1189
00:48:59,200 --> 00:49:00,640
REGENERATION AND CARTILAGE

1190
00:49:00,640 --> 00:49:03,080
IMAGING WHERE SHE PUBLISHED

1191
00:49:03,080 --> 00:49:05,800
EXTENSIVE WILL I SO SHE WILL

1192
00:49:05,800 --> 00:49:07,200
TALK ON BLOOD DERIVED THERAPIES

1193
00:49:07,200 --> 00:49:07,680
FOR OA.

1194
00:49:07,680 --> 00:49:10,880
>>U THAT, SCOTT.  AMYE,
ALSO,

1195
00:49:10,880 --> 00:49:13,280
THANK YOU FOR INTRODUCING WHAT

1196
00:49:13,280 --> 00:49:18,120
WILL BE THE PRIMARY THING OF MY

1197
00:49:18,120 --> 00:49:20,320
TOPIC, THAT IT IS NOT CARTILAGE

1198
00:49:20,320 --> 00:49:25,000
OF BONE CHANGES IN ISOLATION BUT

1199
00:49:25,000 --> 00:49:26,440
RATHER BLACKING AT PEOPLE AS --

1200
00:49:26,440 --> 00:49:28,320
LOOKING AT PEOPLE AS

1201
00:49:28,320 --> 00:49:30,000
INDIVIDUALS, AND TAKING A MORE

1202
00:49:30,000 --> 00:49:33,440
SYSTEMS BASED APPROACH TO

1203
00:49:33,440 --> 00:49:36,000
OSTEOARTHRITIS. SO I AM THANKFUL

1204
00:49:36,000 --> 00:49:38,320
FOR THIS OPPORTUNITY TO TOUCH ON

1205
00:49:38,320 --> 00:49:43,040
THIS ASPECT OF OSTEOARTHRITIS BY

1206
00:49:43,040 --> 00:49:44,720
TALKING ABOUT BLOOD DERIVED

1207
00:49:44,720 --> 00:49:46,240
BIOLOGIC THERAPIES FOR

1208
00:49:46,240 --> 00:49:54,680
OSTEOARTHRITIS. SO MY APPROACH

1209
00:49:54,680 --> 00:49:56,640
TO OSTEOARTHRITIS HAS BEEN EARLY

1210
00:49:56,640 --> 00:49:59,240
DIAGNOSIS AND EARLY TREATMENT TO

1211
00:49:59,240 --> 00:50:01,280
PREVENTED OR DELAY ONSET OF

1212
00:50:01,280 --> 00:50:02,720
OSTEOARTHRITIS. SO REALLY THE

1213
00:50:02,720 --> 00:50:05,280
GOAL IS TO TRANSFORM OUR

1214
00:50:05,280 --> 00:50:06,480
CLINICAL APPROACH FROM SAYING

1215
00:50:06,480 --> 00:50:08,680
OH, THERE IS NOTHING WE CAN DO

1216
00:50:08,680 --> 00:50:12,240
OR PALIATION, TOWARDS PREVENES

1217
00:50:12,240 --> 00:50:13,280
AND TOWARDS EARLY TREATMENT

1218
00:50:13,280 --> 00:50:20,760
THERAPIES.  SO BLOOD REALLY

1219
00:50:20,760 --> 00:50:23,680
REFLECTS WHAT IS GOING ON IN THE

1220
00:50:23,680 --> 00:50:27,000
HUMAN BODY. AND I AM IN SPORTS

1221
00:50:27,000 --> 00:50:30,600
MEDICINE, AND THE PUBLIC, THE

1222
00:50:30,600 --> 00:50:33,040
AMERICAN PUBLIC LOVES SPORTS.

1223
00:50:33,040 --> 00:50:35,360
AND SO I WAS IN PITTSBURGH AT

1224
00:50:35,360 --> 00:50:36,880
THE TIME WHEN WE WERE BATTLING

1225
00:50:36,880 --> 00:50:41,880
FOR ONE OF OUR SUPERBOWL

1226
00:50:41,880 --> 00:50:48,120
CHAMPIONSHIPS, AND THE ANC

1227
00:50:48,120 --> 00:50:50,640
CHAMPIONSHIP FINALS, TOURISM CL

1228
00:50:50,640 --> 00:50:52,400
AND THE SUPERBOWL WAS TWO WEEKS

1229
00:50:52,400 --> 00:50:56,040
AWAY. SO AT THAT TIME HE

1230
00:50:56,040 --> 00:50:59,800
RECEIVED A NEW TREATMENT A NEW

1231
00:50:59,800 --> 00:51:01,600
TREATMENT. NOT ONLY WAS HE BACK

1232
00:51:01,600 --> 00:51:05,520
ON THE FIELD BUT HE CAUGHT TWO

1233
00:51:05,520 --> 00:51:10,120
INNING TOUCHDOWNS AND NAMED

1234
00:51:10,120 --> 00:51:13,360
SUPERMVP. THE LITERATURE OF

1235
00:51:13,360 --> 00:51:17,880
ASTHMA EXPLODED AND IS MOST

1236
00:51:17,880 --> 00:51:20,880
PEOPLE KNOW ERP IS TOUTED AS

1237
00:51:20,880 --> 00:51:25,840
BEING USEFUL FOR EVERYTHING FROM

1238
00:51:25,840 --> 00:51:28,360
TREATING BALDNESS TO ALL ACHES

1239
00:51:28,360 --> 00:51:32,000
AND PAINS SO OF COURSE IT HAS

1240
00:51:32,000 --> 00:51:34,880
BEEN EVALUATED AND USED IN THE

1241
00:51:34,880 --> 00:51:36,000
TREATMENT OF OSTEOARTHRITIS. I

1242
00:51:36,000 --> 00:51:39,840
JUST WANT TO HIGHLIGHT SOME OF

1243
00:51:39,840 --> 00:51:44,680
THE EARLIER ARTICLES GOT IT

1244
00:51:44,680 --> 00:51:46,880
RIGHT.  HE GOT NOT JUST

1245
00:51:46,880 --> 00:51:49,840
PLATELETS BUT HE GOT PLASMA AND

1246
00:51:49,840 --> 00:51:53,400
IT IS A PROMISING TREATMENT FOR

1247
00:51:53,400 --> 00:51:57,320
ATHLETES IN BLOOD AND ALSO THERE

1248
00:51:57,320 --> 00:52:00,800
IS INCLUDING TIGER WOODS HAVE

1249
00:52:00,800 --> 00:52:11,360
PUBLICLY RECEIVED PRP TREATMENT

1250
00:52:12,080 --> 00:52:13,360
THE PUBLIC INTEREST HAS GROWN

1251
00:52:13,360 --> 00:52:16,320
FROM THERE. PRP IS ILL DEFINED

1252
00:52:16,320 --> 00:52:19,480
GENERALLY, HOWEVER, IT IS A

1253
00:52:19,480 --> 00:52:23,200
BLOOD PRODUCT AND REGULATED AS A

1254
00:52:23,200 --> 00:52:27,720
BLOOD PRODUCT. THE USE GOES BACK

1255
00:52:27,720 --> 00:52:30,480
DECADES. WE HAVE HEARD MANY

1256
00:52:30,480 --> 00:52:33,880
DEFINITIONS, BUT ESSENTIALLY IN

1257
00:52:33,880 --> 00:52:35,920
THE CODES OF FEDERAL REGULATIONS

1258
00:52:35,920 --> 00:52:43,600
IT STATES CLEARLY IN 640.34, PRP

1259
00:52:43,600 --> 00:52:44,920
PRODUCTS SHOULD HAVE AT LEAST

1260
00:52:44,920 --> 00:52:47,040
250,000 PLATELETS PER

1261
00:52:47,040 --> 00:52:48,440
MICROLITER. SO THOSE WHO

1262
00:52:48,440 --> 00:52:50,000
MEASURED THE PLATELET COUNTS

1263
00:52:50,000 --> 00:52:53,080
KNOW SOME HAVE THAT, ALREADY IN

1264
00:52:53,080 --> 00:52:55,080
THEIR PLASMA. AND OTHERS HAVE

1265
00:52:55,080 --> 00:53:02,120
LEVELS BELOW THIS. SO IN THE USE

1266
00:53:02,120 --> 00:53:03,600
FOR OSTEOARTHRITIS, THE QUESTION

1267
00:53:03,600 --> 00:53:07,000
IS, DOES THIS WORK? I THINK THAT

1268
00:53:07,000 --> 00:53:13,920
IS VERY DIFFICULT TO ANSWER FOR

1269
00:53:13,920 --> 00:53:16,000
VARIETY OF REASONS, LOOK AT

1270
00:53:16,000 --> 00:53:17,840
STUDIES OVER THE YEARS DOING

1271
00:53:17,840 --> 00:53:23,680
SOME OF MY OWN RESEARCH AND ALSO

1272
00:53:23,680 --> 00:53:30,880
READING STUDIES OF OTHERS, IT

1273
00:53:30,880 --> 00:53:32,320
BILLS DOWN TO IT DEPENDS,

1274
00:53:32,320 --> 00:53:33,680
DEPENDS ON THE QUALITY OF

1275
00:53:33,680 --> 00:53:35,880
PATIENT HEALTH AND THEIR BLOOD

1276
00:53:35,880 --> 00:53:38,400
AT THE TIME THE AUTOLOGOUS PRP

1277
00:53:38,400 --> 00:53:47,480
IS PREPARED. A RECENT STUDY,

1278
00:53:47,480 --> 00:53:54,680
HAVING TROUBLE ADVANCING. VERY

1279
00:53:54,680 --> 00:53:58,680
WELL DONE STUFF OUT OF VAILIA, A

1280
00:53:58,680 --> 00:53:59,640
RANDOMIZED PLACEBO CONTROLLED

1281
00:53:59,640 --> 00:54:04,400
CLINICAL TRIAL. THEY LOOKED AT A

1282
00:54:04,400 --> 00:54:07,920
RELATIVELY EARLY OA POPULATION.

1283
00:54:07,920 --> 00:54:10,560
SO AMYE SHOWED EMAILS AND I KNOW

1284
00:54:10,560 --> 00:54:12,920
MY OWN INBOX IS FLOODED WITH

1285
00:54:12,920 --> 00:54:15,880
EMAILS FROM PEOPLE WHO ARE

1286
00:54:15,880 --> 00:54:18,080
LOOKING FOR THIS TREATMENT AS

1287
00:54:18,080 --> 00:54:19,320
ALTERNATIVE TO JOINT

1288
00:54:19,320 --> 00:54:20,680
REPLACEMENT. IN THIS STUDY THAT

1289
00:54:20,680 --> 00:54:23,320
THEY LOOKED AT EARLIER GRADES OF

1290
00:54:23,320 --> 00:54:26,800
OSTEOARTHRITIS AND REALLY SHOWED

1291
00:54:26,800 --> 00:54:27,800
THAT THERE WAS NO DIFFERENCE

1292
00:54:27,800 --> 00:54:30,160
MANY THE MAIN OUTCOMES BETWEEN

1293
00:54:30,160 --> 00:54:33,040
PLATELET RICH PLASMA AND SALINE.

1294
00:54:33,040 --> 00:54:37,080
THEIR MAIN PLATELET COUNT DID

1295
00:54:37,080 --> 00:54:41,720
MEET FDA ROLES. SO I KNOW THEIR

1296
00:54:41,720 --> 00:54:43,400
CRITICISMS OF THIS STUDY, I

1297
00:54:43,400 --> 00:54:46,120
WOULD ENCOURAGE EVERYONE WHO IS

1298
00:54:46,120 --> 00:54:49,200
INTERESTED TO READ IT THOROUGHLY

1299
00:54:49,200 --> 00:54:51,000
INCLUDING THE ADVANCE PLEASE,

1300
00:54:51,000 --> 00:54:55,200
THE APPENDICES, BECAUSE I -- THE

1301
00:54:55,200 --> 00:55:00,880
QUALITY OF THIS STUDY IS QUITE

1302
00:55:00,880 --> 00:55:02,600
GOOD IN MY OPINION. MY OWN WORK,

1303
00:55:02,600 --> 00:55:07,080
THIS IS STILL ONGOING, AT SIX

1304
00:55:07,080 --> 00:55:09,400
MONTH FOLLOW-UP WED 100%

1305
00:55:09,400 --> 00:55:10,680
FOLLOW-UP IN THE PATIENT

1306
00:55:10,680 --> 00:55:13,520
REPORTED OUTCOMES. ESSENTIALLY

1307
00:55:13,520 --> 00:55:18,280
THE MEAN OUTCOMES DO SHOW

1308
00:55:18,280 --> 00:55:19,600
IMPROVEMENT IN PAIN STIFFNESS

1309
00:55:19,600 --> 00:55:21,800
AND FUNCTION. THOSE WHO NOW

1310
00:55:21,800 --> 00:55:23,640
REACHED TWO YEARS, FOLLOW-UP, I

1311
00:55:23,640 --> 00:55:26,560
EVALUATED SOME IN CLINIC, AFTER

1312
00:55:26,560 --> 00:55:29,640
THEY FILLED OUT THEIR PATIENT

1313
00:55:29,640 --> 00:55:34,240
REPORTED OUTCOMES. WHAT I CAN

1314
00:55:34,240 --> 00:55:42,280
SAY IS WE DO SEE SYMPTOMATIC

1315
00:55:42,280 --> 00:55:43,440
FUNCTIONAL IMPROVEMENT, I WILL

1316
00:55:43,440 --> 00:55:45,880
SHOW YOU THE GATE STUDIES. CAN

1317
00:55:45,880 --> 00:55:56,400
WE GO BACK PLEASE. WE ARE DOING

1318
00:55:59,120 --> 00:56:00,600
GATE STUDIES AND LOOK AT

1319
00:56:00,600 --> 00:56:02,320
PROTEOMIC PROFILES OF INJECTED

1320
00:56:02,320 --> 00:56:04,880
PRP. WHAT THIS SHOWS IS THAT

1321
00:56:04,880 --> 00:56:07,120
PATIENTS WHO REPORT PAIN RELIEF,

1322
00:56:07,120 --> 00:56:09,840
THEY VISIBLY WALK BETTER. IF WE

1323
00:56:09,840 --> 00:56:11,640
CRITICALLY ROOK AT OUR DATA, IT

1324
00:56:11,640 --> 00:56:15,040
IS LESS THAN HALF OF PATIENTS

1325
00:56:15,040 --> 00:56:18,120
WHO HAVE THIS SUSTAINED

1326
00:56:18,120 --> 00:56:19,320
IMPROVEMENT THROUGH SIX MONTHS,

1327
00:56:19,320 --> 00:56:23,920
NOW THROUGH TWO YEARS. THOSE

1328
00:56:23,920 --> 00:56:24,400
PATIENTS RAVE ABOUT THE

1329
00:56:24,400 --> 00:56:26,160
TREATMENT. BUT I CAN GO NEXT

1330
00:56:26,160 --> 00:56:30,560
DOOR INTO THE NEXT PATIENT ROOM

1331
00:56:30,560 --> 00:56:31,600
AND FIND ANOTHER PATIENT WHO IS

1332
00:56:31,600 --> 00:56:38,440
NOT AS HAPPY M. SO YOU CAN SEE

1333
00:56:38,440 --> 00:56:41,800
WHERE THE IDEA THAT PRP WORKS

1334
00:56:41,800 --> 00:56:44,320
FOR KNEE OA CONTINUES TO

1335
00:56:44,320 --> 00:56:46,080
PERPETUATE ITSELF BECAUSE SOME

1336
00:56:46,080 --> 00:56:50,920
PATIENTS AFTER RECEIVING THIS

1337
00:56:50,920 --> 00:56:53,200
TREATMENT DO HAVE SUSS

1338
00:56:53,200 --> 00:56:54,840
SANESYMPTOMATIC AND FUNCTIONAL

1339
00:56:54,840 --> 00:56:57,320
RELIEF. IF WE -- SUSTAINED

1340
00:56:57,320 --> 00:56:59,240
SIMILAR TO MADIC RELIEF. IF WE

1341
00:56:59,240 --> 00:57:01,160
DRAW DOWN AND LOOK AT PREDICTORS

1342
00:57:01,160 --> 00:57:03,560
OF RESPONSE I COME UP EMPTY. 

1343
00:57:03,560 --> 00:57:07,800
THESE ARE OUR PROPOSED OUTCOMES.

1344
00:57:07,800 --> 00:57:10,680
AND THE ONLY THROUGH PCA

1345
00:57:10,680 --> 00:57:14,760
ANALYSIS, WE DID FIND A FEW

1346
00:57:14,760 --> 00:57:17,000
CYTOKINES THAT DID NEGATIVELY

1347
00:57:17,000 --> 00:57:19,840
RELATE, THE HIGHER LEVELS OF

1348
00:57:19,840 --> 00:57:21,080
CYTOKINES, THE MORE PAIN

1349
00:57:21,080 --> 00:57:23,840
PATIENTS REPORTED AT BASELINE

1350
00:57:23,840 --> 00:57:26,360
BUT THESE DIDN'T PREDICT HOW

1351
00:57:26,360 --> 00:57:30,320
WELL THE PATIENT WOULD RESPOND. 

1352
00:57:30,320 --> 00:57:31,760
SO SEVERAL YEARS AGO WE LOOKED

1353
00:57:31,760 --> 00:57:35,160
AT THE PRP AND COMPARED THE PRP

1354
00:57:35,160 --> 00:57:38,400
FROM OLDER MALES WITH KNEE

1355
00:57:38,400 --> 00:57:40,280
OSTEOARTHRITIS AND THAT OF YOUNG

1356
00:57:40,280 --> 00:57:43,120
HEALTHY PRIMARILY MEDICAL

1357
00:57:43,120 --> 00:57:45,680
STUDENTS. WE FOUND THE PRP FROM

1358
00:57:45,680 --> 00:57:49,320
OLDER MALES DEPRESSED

1359
00:57:49,320 --> 00:57:52,280
CHONDROCYTE METABOLISM AND

1360
00:57:52,280 --> 00:57:55,040
UPREGULATED INFLAMMATION. SO I

1361
00:57:55,040 --> 00:57:56,280
HOPE THE MOVIES IN THE NEXT

1362
00:57:56,280 --> 00:58:01,880
SLIDE WILL WORK. WHAT I AM

1363
00:58:01,880 --> 00:58:05,800
SHOWING HERE IS GIVING THE THE

1364
00:58:05,800 --> 00:58:09,160
PRP TO MONOCYTE CULTURES AND

1365
00:58:09,160 --> 00:58:12,120
FINDING THAT THE PRP FROM THE

1366
00:58:12,120 --> 00:58:15,440
YOUNG HEALTHY MOUSE INDUCED THE

1367
00:58:15,440 --> 00:58:18,000
FORMATION OF THE M 2 MACROPHAGE

1368
00:58:18,000 --> 00:58:19,320
PHENOTYPE. WHEREAS IF WE GAVE

1369
00:58:19,320 --> 00:58:25,040
THE PRP THE OLDER MALES, IT

1370
00:58:25,040 --> 00:58:28,680
INDUCED THE M 1 PHENOTYPE. O SO

1371
00:58:28,680 --> 00:58:31,680
I WANT TO TAKE US BACK TO SOME

1372
00:58:31,680 --> 00:58:36,960
OF THE PARABAYOUSIS STUDIES DONE

1373
00:58:36,960 --> 00:58:41,600
BY TOM RANDO NOW PUBLISHED IN

1374
00:58:41,600 --> 00:58:43,840
2004, 2005 WHERE THEY CONNECTED

1375
00:58:43,840 --> 00:58:48,600
THE BLOOD SUPPLY OF YOUNG MICE,

1376
00:58:48,600 --> 00:58:50,440
REALLY THESE STUDIES SHOULD GIVE

1377
00:58:50,440 --> 00:58:56,400
A LOT OF HOPE. THE OLDER MICE

1378
00:58:56,400 --> 00:58:59,920
WITH AGED STEM CELLS IN AGED

1379
00:58:59,920 --> 00:59:01,600
SYSTEM, ACTUALLY WHEN CONNECTED

1380
00:59:01,600 --> 00:59:04,080
TO BLOOD SUPPLY AND ALSO THE

1381
00:59:04,080 --> 00:59:07,840
MILIEU OF YOUNGER MICE, STEM

1382
00:59:07,840 --> 00:59:09,160
CELLS SHOWED GREATER

1383
00:59:09,160 --> 00:59:11,720
REGENERATIVE CAPACITY. OTHERS

1384
00:59:11,720 --> 00:59:19,120
HAVE SHOWN HEALTHIER HEARTS, IN

1385
00:59:19,120 --> 00:59:22,440
WYSS COREY, BETTER MEMORY. THESE

1386
00:59:22,440 --> 00:59:24,000
STUDIES ILLUSTRATE THERE ARE

1387
00:59:24,000 --> 00:59:25,240
CIRCULATING FACTORS IN THE BLOOD

1388
00:59:25,240 --> 00:59:27,320
THAT HELP TO PROMOTE AND CAN

1389
00:59:27,320 --> 00:59:32,280
KICK START AND JUMP START

1390
00:59:32,280 --> 00:59:33,640
REGENERATION IN OLDER

1391
00:59:33,640 --> 00:59:35,280
INDIVIDUALS AND EVEN PEOPLE WHO

1392
00:59:35,280 --> 00:59:37,320
HAVE DISEASE. BUT THE FLIP SIDE

1393
00:59:37,320 --> 00:59:40,560
IS, IF YOU LOOK AT THE ACTUAL

1394
00:59:40,560 --> 00:59:41,760
DATA THE YOUNG MICE WHO WERE

1395
00:59:41,760 --> 00:59:46,160
CONNECTED TO THE OLDER MICE,

1396
00:59:46,160 --> 00:59:49,560
THEIR PROLIFERATIVE STATUS,

1397
00:59:49,560 --> 00:59:52,800
INFLAMMATORY STATUS WAS LORE

1398
00:59:52,800 --> 00:59:54,200
THAN THAT OF YOUNGER MICE

1399
00:59:54,200 --> 00:59:55,440
CONNECTED TO OTHER YOUNG MICE.

1400
00:59:55,440 --> 00:59:57,680
SO WHAT THIS MYLIGHTS IS THERE

1401
00:59:57,680 --> 01:00:00,960
IS GOOD BLOOD AND BAD BLOOD.

1402
01:00:00,960 --> 01:00:02,680
THERE ARE ANYTHINGTIVE INHIBITOR

1403
01:00:02,680 --> 01:00:06,440
FACTORS IN BLOOD OF OLDER MICE. 

1404
01:00:06,440 --> 01:00:10,080
THIS IS AN AREA PRIMED FOR

1405
01:00:10,080 --> 01:00:13,400
RESEARCH. WYSS COREY WENT TO

1406
01:00:13,400 --> 01:00:15,920
SHOW YOU CAN GIVE INJECTIONS OF

1407
01:00:15,920 --> 01:00:17,360
FRESH YOUNG PLASMA AND SEE

1408
01:00:17,360 --> 01:00:19,600
IMPROVED LEARNING MEMORY IN AGED

1409
01:00:19,600 --> 01:00:20,840
MICE AND THEY HAVE DONE CLINICAL

1410
01:00:20,840 --> 01:00:25,400
TRIALS IN THIS AREA. MORE

1411
01:00:25,400 --> 01:00:30,360
RECENTLY, CONVOY'S GROUP HAS

1412
01:00:30,360 --> 01:00:34,880
SHOWN PLASMA DILUTION WILL

1413
01:00:34,880 --> 01:00:37,840
ATTENUATE NEUROINFLAMMATION IN

1414
01:00:37,840 --> 01:00:40,200
OLDS MICE SO THIS TO ME IS VERY

1415
01:00:40,200 --> 01:00:44,480
EXCITING. THEY FURTHER SHOWED --

1416
01:00:44,480 --> 01:00:48,680
THEY ALSO LOOK AT USE OF

1417
01:00:48,680 --> 01:00:51,240
ANTI-SINOLITIC AGENT, A

1418
01:00:51,240 --> 01:00:54,080
PERIPHERALLY ACTIVE AGENT AND

1419
01:00:54,080 --> 01:00:59,040
THEY FOUND THE PLASMA DILUTION

1420
01:00:59,040 --> 01:01:02,400
HAD GREATER ANTI-INFLAMMATORY

1421
01:01:02,400 --> 01:01:03,760
AND REJUVENATIVE EFFECTS BEEN

1422
01:01:03,760 --> 01:01:06,440
THE ANTI-SINOLITIC AGENTS, WE

1423
01:01:06,440 --> 01:01:10,480
HAVE IN OUR GROUP TODAY JOHNNY

1424
01:01:10,480 --> 01:01:13,720
HUARD, JENNY ELISSEEFF AND

1425
01:01:13,720 --> 01:01:15,440
OTHERS WHO ARE ACTIVELY WORKING

1426
01:01:15,440 --> 01:01:19,600
ON ANTI-S XENOLYTICS SO GREAT TO

1427
01:01:19,600 --> 01:01:22,720
HEAR THEIR PERSPECTIVES. BACK TO

1428
01:01:22,720 --> 01:01:28,440
WHAT WE CAN DO TODA TODAY. THISS

1429
01:01:28,440 --> 01:01:29,760
AMYE'S QUESTION, WHAT PATIENTS

1430
01:01:29,760 --> 01:01:33,000
ARE IS INTERESTED IN. THE YOUNG

1431
01:01:33,000 --> 01:01:35,800
PRP SHOWED LOWER LEVELS OF

1432
01:01:35,800 --> 01:01:37,040
INFLAMMATION WITH RED IN OUR

1433
01:01:37,040 --> 01:01:38,520
SCALE REFLECTING HIGHER LEVELS

1434
01:01:38,520 --> 01:01:42,920
OF INFLAMMATION.  BUT I WANT TO

1435
01:01:42,920 --> 01:01:44,680
POINT OUT IT WASN'T EVERYONE,

1436
01:01:44,680 --> 01:01:46,160
THIS YOUNG MAN CERTAINLY SHOWED

1437
01:01:46,160 --> 01:01:50,480
HIGH LEVELS OF INFLAMMATION.  

1438
01:01:50,480 --> 01:01:55,920
AND I LATER LEARN HE FREQUENTED

1439
01:01:55,920 --> 01:02:01,000
MCDONALDS. SO THINGS WE CAN

1440
01:02:01,000 --> 01:02:03,320
THINK OF HEALTH PROMOTION, LIFE

1441
01:02:03,320 --> 01:02:07,200
SPAN PROMOTION IS THINGS WE READ

1442
01:02:07,200 --> 01:02:09,200
ABOUT. AFTER EATING A FAST FOOD

1443
01:02:09,200 --> 01:02:10,640
BURGER NEGATIVE THINGS HAPPEN

1444
01:02:10,640 --> 01:02:16,920
AND PROMOTION AND INFLAMMATION

1445
01:02:16,920 --> 01:02:23,160
HAS BEEN FOUND SO PROFOUND IT IS

1446
01:02:23,160 --> 01:02:24,520
LIKENED TO HAVING A BACTERIAL

1447
01:02:24,520 --> 01:02:27,000
INFECTION. SO WHAT I REALLY LIKE

1448
01:02:27,000 --> 01:02:30,000
TO HIGHLIGHT IS THAT BLOOD

1449
01:02:30,000 --> 01:02:33,760
TREATMENTS PARTICULARLY IN OUR

1450
01:02:33,760 --> 01:02:36,200
ATHLETICALLY GIFTED YOUNG ACTIVE

1451
01:02:36,200 --> 01:02:37,680
ATHLETES, THEIR BLOOD LIKELY HAS

1452
01:02:37,680 --> 01:02:41,840
MORE REGENERATIVE FACTORS THAN

1453
01:02:41,840 --> 01:02:48,240
WHAT IS IN OUR OLDER PATIENTS

1454
01:02:48,240 --> 01:02:49,040
WITH OSTEOARTHRITIS WHO AREN'T

1455
01:02:49,040 --> 01:02:51,680
ABLE TO EXERCISE, EXERCISE IS

1456
01:02:51,680 --> 01:02:56,480
SHOWN TO ENHANCE THE QUALITIES

1457
01:02:56,480 --> 01:02:59,640
AND THE PLATELET RICH PLASMA AND

1458
01:02:59,640 --> 01:03:03,720
ALSO STEM CELL FACTORS THERE IS

1459
01:03:03,720 --> 01:03:06,160
AN EMERGING LITERATURE ON THE

1460
01:03:06,160 --> 01:03:08,960
GUT MICROBIOME JOINT CONNECTION

1461
01:03:08,960 --> 01:03:10,480
AND AMYE ALREADY TOLD US THE

1462
01:03:10,480 --> 01:03:13,600
STRESS OF LOSING HER HOME REALLY

1463
01:03:13,600 --> 01:03:18,000
CHANGED THE INFLAMMATORY

1464
01:03:18,000 --> 01:03:19,560
ENVIRONMENT. SO THESE ARE

1465
01:03:19,560 --> 01:03:20,920
SYSTEMIC FACTORS AND I WANT TO

1466
01:03:20,920 --> 01:03:23,040
HIGHLIGHT WE NEED TO TAKE THIS

1467
01:03:23,040 --> 01:03:27,680
AS A SYSTEMS BASED APPROACH AND

1468
01:03:27,680 --> 01:03:29,000
THINK HOW WE CAN OPTIMIZE

1469
01:03:29,000 --> 01:03:30,880
SYSTEMIC BIOLOGY FOR JOINT

1470
01:03:30,880 --> 01:03:34,320
HEALTH. I BELIEVE THIS WILL BE

1471
01:03:34,320 --> 01:03:35,920
REFLECTED IN THE BLOOD WHICH

1472
01:03:35,920 --> 01:03:37,120
CIRCUMSTANCE RATES THROUGHOUT

1473
01:03:37,120 --> 01:03:43,040
THE SYSTEM. AND PRP IF USING AS

1474
01:03:43,040 --> 01:03:45,400
TREATMENT FOR OUR BONE MARROW SO

1475
01:03:45,400 --> 01:03:48,040
PREPARATIONS WILL LIKELY BE

1476
01:03:48,040 --> 01:03:50,440
ENHANCED IN REGION OPERATIVE

1477
01:03:50,440 --> 01:03:51,920
CAPACITY. THIS IS OPINION RIGHT

1478
01:03:51,920 --> 01:03:55,680
NOW. BUT THESE ARE THE STUDIES,

1479
01:03:55,680 --> 01:04:00,400
THAT CAN REALLY HIGHLIGHT

1480
01:04:00,400 --> 01:04:02,080
WHETHER DIET AND LIFESTYLE

1481
01:04:02,080 --> 01:04:03,680
IMPROVEMENT TODAY CAN IMPROVE

1482
01:04:03,680 --> 01:04:05,840
SYMPTOMS.  THESE ARE AREAS WHERE

1483
01:04:05,840 --> 01:04:08,960
PATIENTS CAN ALREADY START

1484
01:04:08,960 --> 01:04:13,000
FOLLOWING GUIDELINES SHOWN TO BE

1485
01:04:13,000 --> 01:04:19,120
HEART HEALTHY FOR THE BRAIN AND

1486
01:04:19,120 --> 01:04:20,200
OVERALL HEALTH IN GENERAL. THANK

1487
01:04:20,200 --> 01:04:24,760
YOU FOR YOUR ATTENTION. HAPPY TO

1488
01:04:24,760 --> 01:04:28,280
TAKE QUESTIONS OR TO DONATE TIME

1489
01:04:28,280 --> 01:04:33,840
BACK TO THE PROGRAM.

1490
01:04:33,840 --> 01:04:36,520
>>TWO QUESTIONS, WE HAVE
BEEN

1491
01:04:36,520 --> 01:04:37,520
CHATTING BEHIND THE SCENES AND

1492
01:04:37,520 --> 01:04:40,160
WE ARE GOING TO TAKE TEN MINUTES

1493
01:04:40,160 --> 01:04:42,720
OUT OF THE LUNCH AND FIVE

1494
01:04:42,720 --> 01:04:44,360
MINUTES OUTS OF THE BREAK TO GET

1495
01:04:44,360 --> 01:04:46,560
US CAUGHT UP SO IT IS MORE

1496
01:04:46,560 --> 01:04:47,560
IMPORTANT WE HAVE A DISCUSSION. 

1497
01:04:47,560 --> 01:04:50,240
>>I HAVE A QUESTION.

1498
01:04:50,240 --> 01:04:50,920
>>YES.

1499
01:04:50,920 --> 01:04:54,400
>>GREAT TALK. THANK YOU.
THE

1500
01:04:54,400 --> 01:04:59,440
AUSTRALIAN STUDY YOU MENTIONED

1501
01:04:59,440 --> 01:05:01,560
WAS PRP CONCENTRATION THAT WAS

1502
01:05:01,560 --> 01:05:06,480
FAIRLY LOW BY OTHER TYPES OF

1503
01:05:06,480 --> 01:05:08,760
PRP. DEVICES. SO IN YOUR STUDY

1504
01:05:08,760 --> 01:05:12,920
WHICH YOU DID SHOW SOME POSITIVE

1505
01:05:12,920 --> 01:05:14,720
RESULTS, WHAT WAS YOUR PERCENT

1506
01:05:14,720 --> 01:05:17,120
-- CONCENTRATION ABOVE BASELINE,

1507
01:05:17,120 --> 01:05:18,600
HOW DID IT COMPARE WITH THAT

1508
01:05:18,600 --> 01:05:19,960
STUDY?

1509
01:05:19,960 --> 01:05:24,040
>>YES. SO MINE WAS
SIMILAR TO

1510
01:05:24,040 --> 01:05:28,760
THAT STUDY. SO REALLY FOR US TO

1511
01:05:28,760 --> 01:05:31,400
DO THIS TRIAL, THIS IS AT THE

1512
01:05:31,400 --> 01:05:33,000
VETERANS HOSPITAL, WE WEREN'T

1513
01:05:33,000 --> 01:05:36,840
ABLE TO MAKE OUR OWN PRP OR HAVE

1514
01:05:36,840 --> 01:05:44,840
DEFINED CONCENTRATIONS IN THESE

1515
01:05:44,840 --> 01:05:45,640
COMMERCIALLY AVAILABLE SYSTEM,

1516
01:05:45,640 --> 01:05:47,200
IT WAS THE OLD SYSTEM AND WE

1517
01:05:47,200 --> 01:05:52,720
HAVE BEEN ABLE TO HAVE A WORK

1518
01:05:52,720 --> 01:05:53,760
AROUND, AND CONTINUE WITH THAT.

1519
01:05:53,760 --> 01:05:56,080
I HEAR WHAT YOU ARE SAYING,

1520
01:05:56,080 --> 01:05:59,680
OTHERS DO AND STUDIES SHOW IS IT

1521
01:05:59,680 --> 01:06:03,960
5X BASELINE, 3X BASELINE. WE

1522
01:06:03,960 --> 01:06:06,080
WERE RIGHT AROUND CLOSE TO WHERE

1523
01:06:06,080 --> 01:06:07,600
THE AUSTRALIAN STUDY WAS.

1524
01:06:07,600 --> 01:06:09,000
>>OKAY. THANK YOU.

1525
01:06:09,000 --> 01:06:13,680
>>YES.

1526
01:06:13,680 --> 01:06:20,120
>>I THINK WE C WE CAN GET
CUSTD

1527
01:06:20,120 --> 01:06:22,360
PRP TO SAY THIS IS IS A GOOD

1528
01:06:22,360 --> 01:06:23,440
SPECIMEN, CAN WE USE THIS DATA

1529
01:06:23,440 --> 01:06:25,440
TO IDENTIFY CHARACTERIZE PRP.

1530
01:06:25,440 --> 01:06:32,760
>>YES. I THINK MANY IN
THIS

1531
01:06:32,760 --> 01:06:34,560
ROOM ARE IS LOOKING INTO THOSE

1532
01:06:34,560 --> 01:06:38,640
QUESTIONS, AND REALLY ONE OF THE

1533
01:06:38,640 --> 01:06:42,480
FIRST STEPS IS THE PARABAYOUSIS

1534
01:06:42,480 --> 01:06:47,640
STUDIES AND EARLIER IN VITRO

1535
01:06:47,640 --> 01:06:48,720
STUDY, FOR SOME PEOPLE,

1536
01:06:48,720 --> 01:06:50,080
PARTICULARLY HOLDER PEOPLE WITH

1537
01:06:50,080 --> 01:06:53,280
MORE SEVERE DISEASE, THERE ARE

1538
01:06:53,280 --> 01:06:55,840
LIKELY FACTORS IN THEIR BLOOD WE

1539
01:06:55,840 --> 01:07:00,760
DON'T WANT TO CONCENTRATE WITH

1540
01:07:00,760 --> 01:07:02,640
PRP TYPICALLY YOU ARE

1541
01:07:02,640 --> 01:07:05,040
CONCENTRATING A LITTLE BIT. SO

1542
01:07:05,040 --> 01:07:06,200
POTENTIALLY THINGS LIKE IF YOU

1543
01:07:06,200 --> 01:07:08,280
CAN IDENTIFY WHAT THE BAD

1544
01:07:08,280 --> 01:07:13,440
FACTORS ARE, THEY CAN BE REMO 

1545
01:07:13,440 --> 01:07:16,000
REMOVED. AND I KNOW OTHERS WILL

1546
01:07:16,000 --> 01:07:20,560
SPEAK ON SMALL PROTEINS OR

1547
01:07:20,560 --> 01:07:23,960
EXOSOMES. WE CAN SHOW SOME

1548
01:07:23,960 --> 01:07:25,840
THINGS TO BE BENEFICIAL, THOSE

1549
01:07:25,840 --> 01:07:29,920
CAN POTENTIALLY BE ENHANCED OR

1550
01:07:29,920 --> 01:07:30,800
PATIENTS EVALUATED TO SEE

1551
01:07:30,800 --> 01:07:35,320
WHETHER THEY FALL INTO A

1552
01:07:35,320 --> 01:07:37,000
REGENERATIVE PHENOTYPE AND WOULD

1553
01:07:37,000 --> 01:07:38,440
BE CANDIDATES FOR USE OF THEIR

1554
01:07:38,440 --> 01:07:39,680
OWN BLOOD OR NEED SOME OTHER

1555
01:07:39,680 --> 01:07:41,680
FORMULATION.

1556
01:07:41,680 --> 01:07:48,280
>>DR. HOCHBERG HAS A
QUESTION. 

1557
01:07:48,280 --> 01:07:54,480
>>I JUST UNMUTED MYSELF.
SO THE

1558
01:07:54,480 --> 01:07:57,040
PREPONDERANCE OF EVIDENCE FOR

1559
01:07:57,040 --> 01:08:01,240
PRP, DOES NOT SUPPORT ITS USE.

1560
01:08:01,240 --> 01:08:03,360
DESPITE THE FACT IT IS

1561
01:08:03,360 --> 01:08:04,920
EXTENSIVELY USED, PARTICULARLY

1562
01:08:04,920 --> 01:08:11,200
IN PRACTICE OF SPORTS MEDICINE,

1563
01:08:11,200 --> 01:08:13,240
P FOCI TRY ORTHOPEDIC SURGERY,

1564
01:08:13,240 --> 01:08:14,800
THE RECOMMENDATIONS OF THE

1565
01:08:14,800 --> 01:08:17,480
ARTHRITIS FOUNDATION AND THE

1566
01:08:17,480 --> 01:08:18,560
AMERICAN COLLEGE OF

1567
01:08:18,560 --> 01:08:19,600
RHEUMATOLOGY, AMERICAN ACADEMY

1568
01:08:19,600 --> 01:08:21,400
OF ORTHOPEDIC SURGEON, THE VA

1569
01:08:21,400 --> 01:08:23,960
DEPARTMENT OF DEFENSE, THESE

1570
01:08:23,960 --> 01:08:25,480
RECOMMENDATIONS FOR THE

1571
01:08:25,480 --> 01:08:29,040
NON-SURGICAL MANAGEMENT OF KNEE

1572
01:08:29,040 --> 01:08:30,680
OSTEOARTHRITIS,S DO NOT

1573
01:08:30,680 --> 01:08:40,720
RECOMMEND USE OF PRP.

1574
01:08:40,720 --> 01:08:42,720
>>I THINK THAT -- I USE
IT IN

1575
01:08:42,720 --> 01:08:51,800
MY PRACTICE AT THE VA AND I

1576
01:08:51,800 --> 01:08:53,480
THINK THE WAY I THINK ABOUT IT

1577
01:08:53,480 --> 01:08:57,840
IS WE ARE USING IT IN YOUNGER

1578
01:08:57,840 --> 01:09:02,160
PATIENTS WITH LESS SEVERE

1579
01:09:02,160 --> 01:09:05,560
DISEASE, I TELL ALL MY PATIENTS

1580
01:09:05,560 --> 01:09:08,720
THAT IT DOESN'T WORK WITH

1581
01:09:08,720 --> 01:09:11,520
EVERYONE. MY OPINION BASED ON

1582
01:09:11,520 --> 01:09:15,080
EARLY STUDIES IS HEALTHIER THEY

1583
01:09:15,080 --> 01:09:17,360
CAN GET THEMSELVES THE MORE

1584
01:09:17,360 --> 01:09:20,000
LIKELY IT IS THEIR BLOOD, SO

1585
01:09:20,000 --> 01:09:22,880
THIS IS ESSENTIALLY WHAT I HAVE

1586
01:09:22,880 --> 01:09:26,280
TALKED ABOUT. WHAT WILL BE USED

1587
01:09:26,280 --> 01:09:28,200
BLOOD AND PLATELETS WHICH IS

1588
01:09:28,200 --> 01:09:31,480
REALLY THERAPY WE ARE USING BE

1589
01:09:31,480 --> 01:09:34,040
MORE LIKELY TO HAVE BENEFICIAL

1590
01:09:34,040 --> 01:09:41,080
EFFECTS IN THAT IN SOME INSTA 

1591
01:09:41,080 --> 01:09:43,600
INSTANCES, THE BLOOD SHOULDN'T

1592
01:09:43,600 --> 01:09:44,920
BE CONCENTRATED AND USED. I

1593
01:09:44,920 --> 01:09:46,360
DON'T THINK WE HAVE THE ANSWER.

1594
01:09:46,360 --> 01:09:49,680
THE AMOUNT OF INJECTIONS THAT

1595
01:09:49,680 --> 01:09:52,440
HAVE BEEN GIVEN WOULD

1596
01:09:52,440 --> 01:09:54,960
SUBSTANTIATE NO SIGNIFICANT

1597
01:09:54,960 --> 01:09:56,600
SAFETY CONCERNS, REALLY THE

1598
01:09:56,600 --> 01:10:00,040
QUESTION IS EFFICACY AND THE

1599
01:10:00,040 --> 01:10:02,280
QUANTITATIVE MR WORK HAS NOT

1600
01:10:02,280 --> 01:10:05,280
SHOWN REGENERATIVE CAPACITY.

1601
01:10:05,280 --> 01:10:07,640
>>SO THE QUESTION IS
WHETHER TO

1602
01:10:07,640 --> 01:10:12,840
RECOMMEND OR PROVIDE A TREATMENT

1603
01:10:12,840 --> 01:10:15,320
WHICH WHILE SAFE HAS NOT BEEN

1604
01:10:15,320 --> 01:10:17,520
SHOWN EFFICACIOUS IN CONTROLLED

1605
01:10:17,520 --> 01:10:18,960
CLINICAL TRIALS. I WOULD SAY MY

1606
01:10:18,960 --> 01:10:21,360
COLLEAGUES HERE AT THE VA IN

1607
01:10:21,360 --> 01:10:24,480
MARYLAND WHO ARE IN POSIATRY AND

1608
01:10:24,480 --> 01:10:27,640
ORTHOPEDICS ALSO USE PRP

1609
01:10:27,640 --> 01:10:31,320
INJECTIONSS. MY FELLOWS REFER

1610
01:10:31,320 --> 01:10:36,960
PATIENTS FOR PRP INJECTIONS. BUT

1611
01:10:36,960 --> 01:10:40,400
THE ISSUE WOULD BE WHAT ABOUT

1612
01:10:40,400 --> 01:10:43,120
FOR SYMPTOMATIC THERAPY, ONE CAN

1613
01:10:43,120 --> 01:10:44,240
CONSIDER SALIENT INJECTIONS SO

1614
01:10:44,240 --> 01:10:47,600
THE ISSUE IS WHETHER THERE IS

1615
01:10:47,600 --> 01:10:49,240
EVIDENCE OF REGENERATIVE

1616
01:10:49,240 --> 01:10:52,840
CAPACITY UNQUOTE.  IN THE

1617
01:10:52,840 --> 01:10:54,320
PATIENT WITH NIKOS ARTHRITIS.

1618
01:10:54,320 --> 01:10:57,840
WHO IS DIFFERENT FROM THE YOUNG

1619
01:10:57,840 --> 01:11:00,080
ATHLETE WITH A ISOLATED

1620
01:11:00,080 --> 01:11:01,840
CARTILAGE DEFECT IS WE WILL

1621
01:11:01,840 --> 01:11:08,360
DISCUSS DURING THE DAY TODAY.  I

1622
01:11:08,360 --> 01:11:09,160
WILL GO BACK ON MUTE.

1623
01:11:09,160 --> 01:11:11,040
>>TWO MORE QUESTIONS, DR.

1624
01:11:11,040 --> 01:11:11,440
WHITE.

1625
01:11:11,440 --> 01:11:14,040
>>THANK YOU FOR THAT
WONDERFUL

1626
01:11:14,040 --> 01:11:16,560
PRESENTATION DR. CHU. IT IS

1627
01:11:16,560 --> 01:11:18,320
INTRIGUING WITH HEALTHY

1628
01:11:18,320 --> 01:11:19,680
LIFESTYLE ASSOCIATED RESPONSE

1629
01:11:19,680 --> 01:11:23,120
SEEMS TO PRP OR AT LEAST THAT IS

1630
01:11:23,120 --> 01:11:24,560
HYPOTHESIZED. ANYONE DELVED INTO

1631
01:11:24,560 --> 01:11:27,120
THAT LOOKING AT OBJECTIVELY

1632
01:11:27,120 --> 01:11:28,600
MEASURE HOW ACTIVE SOMEBODY

1633
01:11:28,600 --> 01:11:30,600
ACTUALLY IS, MAYBE IN ADDITION

1634
01:11:30,600 --> 01:11:32,800
TO THEIR DIET AND QUALITIES OF

1635
01:11:32,800 --> 01:11:34,360
HEALTHY LIFESTYLE AND RESPONSE

1636
01:11:34,360 --> 01:11:35,600
TO PRP INJECTION?

1637
01:11:35,600 --> 01:11:38,800
I HAVEN'T COME ACROSS THAT AT

1638
01:11:38,800 --> 01:11:40,640
ALL BUT INTRIGUED BY YOUR

1639
01:11:40,640 --> 01:11:45,280
STATEMENT WITH REGARDS TO THAT. 

1640
01:11:45,280 --> 01:11:48,400
>>I THINK YOUR
BACKGROUNDS

1641
01:11:48,400 --> 01:11:53,000
CERTAINLY WITH WEARABLES AND

1642
01:11:53,000 --> 01:11:54,480
MEASURING THINGS, LEFT TO HAVE

1643
01:11:54,480 --> 01:11:55,120
FURTHER DISCUSSIONS WHERE WE ARE

1644
01:11:55,120 --> 01:11:58,320
WORKING TO IMPLEMENT THOSE TYPES

1645
01:11:58,320 --> 01:12:02,600
OF PROGRAMS INTO ACTUALLY

1646
01:12:02,600 --> 01:12:08,120
CLINICAL PRACTICE. AT THE

1647
01:12:08,120 --> 01:12:11,320
VETERANS HOSPITAL HERE. THESE

1648
01:12:11,320 --> 01:12:12,920
ARE ALL THINGS THAT I THINK NEED

1649
01:12:12,920 --> 01:12:14,720
TO BE LOOKED AT. THANK YOU FOR

1650
01:12:14,720 --> 01:12:15,440
BRINGING THAT UP.

1651
01:12:15,440 --> 01:12:19,680
>>GREAT.  THANKS.

1652
01:12:19,680 --> 01:12:22,960
>>ONE LAST QUICK
QUESTION. WE

1653
01:12:22,960 --> 01:12:24,040
TRY TO STAY ON PROGRAM LALE BIT

1654
01:12:24,040 --> 01:12:26,920
HERE. 

1655
01:12:26,920 --> 01:12:29,240
>>I HAD A COMMENT
REGARDING

1656
01:12:29,240 --> 01:12:31,200
CUSTOMIZATION OF PRP. SOME OF US

1657
01:12:31,200 --> 01:12:32,960
HAVE SHOWN IF YOU WANT TO USE

1658
01:12:32,960 --> 01:12:35,280
PRP FOR SKELETAL MUSCLE, AND IF

1659
01:12:35,280 --> 01:12:38,680
YOU BLOCK TGF BETA 1 YOU GET

1660
01:12:38,680 --> 01:12:40,360
BLOOD FIBROSIS AND IMPROVE

1661
01:12:40,360 --> 01:12:42,960
BENEFIT OF PRP. WE DID THE SAME

1662
01:12:42,960 --> 01:12:46,160
FOR CARTILAGE WITH VGF AND

1663
01:12:46,160 --> 01:12:48,000
ANGIOGENESIS FOR PFP WITH

1664
01:12:48,000 --> 01:12:49,880
CARTILAGE REPAIR. I BELIEVE

1665
01:12:49,880 --> 01:12:53,280
CUSTOMIZATION OF PRP MAYBE MORE

1666
01:12:53,280 --> 01:12:55,040
THAN MINIMAL MANIPULATION OF

1667
01:12:55,040 --> 01:12:57,800
THIS PRODUCT SO I WOULD LIKE TO

1668
01:12:57,800 --> 01:12:59,120
ASK CONNIE, WHAT HAPPENED IF YOU

1669
01:12:59,120 --> 01:13:00,760
INJECT PRP BUT TREAT PATIENT

1670
01:13:00,760 --> 01:13:06,920
WITH FIBROTIC DRUG, LOSARTIN OR

1671
01:13:06,920 --> 01:13:09,000
KOZAR OR BLOOD VEGF THAT PREVENT

1672
01:13:09,000 --> 01:13:10,960
CUSTOMIZATION OF PRP BUT THE

1673
01:13:10,960 --> 01:13:13,200
SAME BENEFIT ON CARTILAGE.

1674
01:13:13,200 --> 01:13:18,840
>>THANKS, I THINK WHAT
YOU ARE

1675
01:13:18,840 --> 01:13:20,520
TALKING ABOUT IS COMBINATION

1676
01:13:20,520 --> 01:13:23,440
TYPE THERAPY WHERE YOU ARE

1677
01:13:23,440 --> 01:13:28,480
LOOKING AT NOT JUST LOOKING AT

1678
01:13:28,480 --> 01:13:36,520
WHETHER THIS HAS REGENERATIVE

1679
01:13:36,520 --> 01:13:38,600
CAPACITY BUT BLOCKING SOMETHING

1680
01:13:38,600 --> 01:13:41,720
THAT MAY BE INHIBITING

1681
01:13:41,720 --> 01:13:44,160
REGENERATION. AND YOUR OTHER

1682
01:13:44,160 --> 01:13:45,720
WORK WITH ANTI-XENOLYTICS,

1683
01:13:45,720 --> 01:13:47,680
TAKING THE APPROACH TO ADDRESS

1684
01:13:47,680 --> 01:13:50,000
BOTH SYSTEMIC ASPECT AND ALSO

1685
01:13:50,000 --> 01:13:53,640
THE LOCAL JOINT ENVIRONMENT I

1686
01:13:53,640 --> 01:13:57,680
THINK THOSE TYPES OF TAKING A

1687
01:13:57,680 --> 01:13:59,840
BROADER LOOK BEYOND CARTILAGE

1688
01:13:59,840 --> 01:14:03,280
AND BEYOND BONE AND ADDRESSING

1689
01:14:03,280 --> 01:14:08,920
THE JOINT ALONG WITH SYSTEMIC

1690
01:14:08,920 --> 01:14:10,920
COMPONENTS PARTICULARLY RELATED

1691
01:14:10,920 --> 01:14:12,760
TO AGE AND OTHER DISEASE

1692
01:14:12,760 --> 01:14:14,960
PROCESSES. CRITICALLY IMPORTANT,

1693
01:14:14,960 --> 01:14:21,560
THANK YOU FOR HIGHLIGHTING THAT 

1694
01:14:21,560 --> 01:14:24,600
>>GEORGE DO YOU WANT TO
ASK A

1695
01:14:24,600 --> 01:14:26,560
QUICK QUESTION? YOU HAVE YOUR

1696
01:14:26,560 --> 01:14:27,040
HAND UP.

1697
01:14:27,040 --> 01:14:31,040
>>MY ONE QUESTION IS
CONNIE,

1698
01:14:31,040 --> 01:14:34,640
YOU POINTED OUT THERE IS A

1699
01:14:34,640 --> 01:14:35,880
SIGNIFICANT PART OF SUCCESS OR

1700
01:14:35,880 --> 01:14:36,880
FAILURE OF CURRENT TREATMENT

1701
01:14:36,880 --> 01:14:39,520
WHICH IS CHOOSING THE RIGHT

1702
01:14:39,520 --> 01:14:43,600
PATIENT. THERE ARE PATIENTS WE

1703
01:14:43,600 --> 01:14:45,320
CAN GUESS OR LESS LIKELY TO

1704
01:14:45,320 --> 01:14:47,320
RESPOND SO VARIOUS AREAS OF

1705
01:14:47,320 --> 01:14:48,720
DISEASE OR STABILITY OF THE

1706
01:14:48,720 --> 01:14:50,520
JOINT OR PAST HISTORY, WEIGHT

1707
01:14:50,520 --> 01:14:54,680
AND AGE. THEN THERE ARE PATIENTS

1708
01:14:54,680 --> 01:14:56,680
WHO MAY BE BAD DONORS BECAUSE

1709
01:14:56,680 --> 01:14:57,880
BLOOD COMPONENTS AT THE TIME

1710
01:14:57,880 --> 01:15:02,240
WHEN WE WANT TO TREAT THEM, ARE

1711
01:15:02,240 --> 01:15:03,880
FLAWED. OTHER THAN THE WORK YOU

1712
01:15:03,880 --> 01:15:06,240
ARE DOING WHERE WE ARE MEASURING

1713
01:15:06,240 --> 01:15:10,400
COMPONENTS IN THE PRP AND

1714
01:15:10,400 --> 01:15:11,520
CHARACTERISTICS IN THE PATIENTS

1715
01:15:11,520 --> 01:15:12,760
ARE WE DESIGNING STUDIES TO

1716
01:15:12,760 --> 01:15:15,120
ALLOW US TO ANSWER THESE TWO

1717
01:15:15,120 --> 01:15:16,400
IMPORTANT QUESTIONS WHO TO TREAT

1718
01:15:16,400 --> 01:15:23,760
AND WHO NOT TO TREAT. 

1719
01:15:23,760 --> 01:15:26,480
>>ID THINK THOSE STUDIES
A

1720
01:15:26,480 --> 01:15:28,480
CRITICALLY IMPORTANT. I HAVE

1721
01:15:28,480 --> 01:15:30,160
SOME UPCOMING STUDIES WHERE WE

1722
01:15:30,160 --> 01:15:31,880
WILL TRY TO ADDRESS THAT BUT IT

1723
01:15:31,880 --> 01:15:35,200
IS NOT -- IT IS SOMETHING THAT I

1724
01:15:35,200 --> 01:15:39,000
THINK FOR THE BROADER COMMUNITY,

1725
01:15:39,000 --> 01:15:41,640
THIS IS A WAY TO APPROACH THIS,

1726
01:15:41,640 --> 01:15:46,280
THAT WE NEED TO DEFINE DIFFERENT

1727
01:15:46,280 --> 01:15:47,600
SUB TYPES. I KNOW YOU HAVE DONE

1728
01:15:47,600 --> 01:15:50,480
WORK IN THIS AREA. SO DEFINING

1729
01:15:50,480 --> 01:15:52,280
STRUCTURAL SUB TYPES, DEFINING

1730
01:15:52,280 --> 01:15:57,360
MOLECULAR SUB TYPES. ALSO

1731
01:15:57,360 --> 01:15:58,480
LOOKING AT DISEASE PRIOR TO

1732
01:15:58,480 --> 01:15:59,600
SYMPTOM ONSET IS CRITICALLY

1733
01:15:59,600 --> 01:16:03,800
IMPORTANT. STUDY AFTER STUDY,

1734
01:16:03,800 --> 01:16:08,840
HAS SHOWN THAT REALLY IT IS ONLY

1735
01:16:08,840 --> 01:16:10,080
ADVANCED BONE ON BONE STRUCTURE

1736
01:16:10,080 --> 01:16:11,280
DISEASE OR PATIENT REPORTED

1737
01:16:11,280 --> 01:16:15,040
OUTCOMES START TO TRACK. YET ALL

1738
01:16:15,040 --> 01:16:17,560
THESE DEVELOP EARLIER LIKE A

1739
01:16:17,560 --> 01:16:19,720
HEART ATTACK, YOU DON'T REALLY

1740
01:16:19,720 --> 01:16:21,920
KNOW UNTIL EVERYTHING CULMINATES

1741
01:16:21,920 --> 01:16:24,920
AND CATASTROPHIC FAILURE AND

1742
01:16:24,920 --> 01:16:26,120
PATIENTS ARE IN PAIN ALL THE

1743
01:16:26,120 --> 01:16:27,080
TIME AND THEN REALLY IT IS TOO

1744
01:16:27,080 --> 01:16:34,200
LATE.  BRING IT BACK TO EARLY OA

1745
01:16:34,200 --> 01:16:36,520
PRE-OA ARE VERY, VERY IMPORTANT 

1746
01:16:36,520 --> 01:16:38,880
>>THANK YOU.

1747
01:16:38,880 --> 01:16:44,160
>>THANK YOU. SO MUCH. IT
GIVES

1748
01:16:44,160 --> 01:16:45,680
ME GREAT PLEASURE TO INTRODUCE

1749
01:16:45,680 --> 01:16:50,320
MY CO-CHAIR, SCOTT RODEO. WHO

1750
01:16:50,320 --> 01:16:53,520
HAS REALLY BEEN DRIVING THOUGHT

1751
01:16:53,520 --> 01:16:56,840
LEADER IN THE AREA OF

1752
01:16:56,840 --> 01:17:01,560
REGENERATIVE MEDICINE, HE IS

1753
01:17:01,560 --> 01:17:04,880
ACCOMPLISHED CLINICIAN SCIENTIST

1754
01:17:04,880 --> 01:17:10,880
NIH FUNDED, HE IS VICE CHAIR

1755
01:17:10,880 --> 01:17:13,880
RESEARCH HOSPITAL FOR SPECIAL

1756
01:17:13,880 --> 01:17:15,600
SURGERY, I KNOW DR. WHITE WAS

1757
01:17:15,600 --> 01:17:19,080
ALSO A GIANTS FAN. HE'S BEEN

1758
01:17:19,080 --> 01:17:22,160
TEAM PHYSICIAN FOR PRO FOOTBALL

1759
01:17:22,160 --> 01:17:23,680
AND OTHER SPORTS FOR MANY, MANY

1760
01:17:23,680 --> 01:17:27,480
YEARS. HE'S GOING TO TALK

1761
01:17:27,480 --> 01:17:29,720
CONCEPTS UNDER ROLE OF STEM

1762
01:17:29,720 --> 01:17:30,400
CELLS IN OSTEOARTHRITIS.

1763
01:17:30,400 --> 01:17:32,000
>>THANK YOU, CONNIE.
LET'S MOVE

1764
01:17:32,000 --> 01:17:41,800
AHEAD.  LET'S TALK CELL THERAPY 

1765
01:17:41,800 --> 01:17:43,880
DISCLOSURES ARE HERE. NOT GOING

1766
01:17:43,880 --> 01:17:45,120
DIRECTLY RELEVANT EXCITE

1767
01:17:45,120 --> 01:17:47,000
HONESTLY. I WILL START ASKING

1768
01:17:47,000 --> 01:17:47,840
THE QUESTION WHAT IS A STEM

1769
01:17:47,840 --> 01:17:51,840
CELL? ARE THERE ANY TRUE QUOTE

1770
01:17:51,840 --> 01:17:53,440
UNQUOTE STEM CELLS WE CAN USE

1771
01:17:53,440 --> 01:17:55,080
TODAY.  WE CAN USE CELLS FROM

1772
01:17:55,080 --> 01:17:57,840
BONE MARROW ADIPOSE TISSUE,

1773
01:17:57,840 --> 01:18:02,520
PERINATAL TISSUE, AMNIOTIC

1774
01:18:02,520 --> 01:18:03,720
MEMBRANE, CORED BLOOD AND THINGS

1775
01:18:03,720 --> 01:18:05,720
LIKE THAT, UNDERSTAND UNIVERSAL

1776
01:18:05,720 --> 01:18:08,720
STEM CELL CRITERIA INCLUDE

1777
01:18:08,720 --> 01:18:11,320
UNSPECIALIZED CELLS THAT HAVE

1778
01:18:11,320 --> 01:18:13,800
POTENTIAL FOR SELF-RENEWAL, THEY

1779
01:18:13,800 --> 01:18:16,640
DIVIDE ASIMILAR METICALLY TO TWO

1780
01:18:16,640 --> 01:18:18,920
DAUGHTER CELLS ONE COPY OF

1781
01:18:18,920 --> 01:18:20,640
ORIGINAL AND SECOND DAUGHTER

1782
01:18:20,640 --> 01:18:23,440
CELL DIFFERENTIATE, THERE'S

1783
01:18:23,440 --> 01:18:24,520
MULTI-POTENT DIFFERENTIATION

1784
01:18:24,520 --> 01:18:27,280
CAPACITY GIVES YOU A SENSE OF

1785
01:18:27,280 --> 01:18:30,640
THE DIFFERENTIATION CAPACITY.

1786
01:18:30,640 --> 01:18:33,000
UTILIZED CELL SOURCES CONTAIN

1787
01:18:33,000 --> 01:18:36,320
FEW IF ANY STEM CELLS BY FORMAL

1788
01:18:36,320 --> 01:18:38,320
CRITERIA. MANY KAPLAN CLASSIC

1789
01:18:38,320 --> 01:18:41,520
1991 PAPER FOR DEFINING

1790
01:18:41,520 --> 01:18:44,160
MESENCHYMAL STEM CELL BACK IN

1791
01:18:44,160 --> 01:18:50,200
THE 1960s AND 70s, SPUE

1792
01:18:50,200 --> 01:18:51,680
FRIEDENSTEEN INTRODUCED BONE

1793
01:18:51,680 --> 01:18:55,040
MARROW AND KAPLAN INTRODUCED

1794
01:18:55,040 --> 01:18:58,680
MESENCHYMAL STEM CELLS IN 1991,

1795
01:18:58,680 --> 01:19:00,120
PROGENY BECOME COMMITTED TO

1796
01:19:00,120 --> 01:19:01,240
PHENOTYPIC PATHWAY LEADING TO

1797
01:19:01,240 --> 01:19:02,560
DIFFERENTIATION. THIS IS A

1798
01:19:02,560 --> 01:19:05,480
CONCEPT BACK THROUGH THE '90s,

1799
01:19:05,480 --> 01:19:08,240
ORAL CAPLAN AND OTHERS WORK. HE

1800
01:19:08,240 --> 01:19:10,040
TALKED ABOUT EXTRINSIC FACTORS

1801
01:19:10,040 --> 01:19:12,680
AS WELL AS INTRINSIC FACTORS IN

1802
01:19:12,680 --> 01:19:15,760
THE CELLS WITH EACH STEP TO

1803
01:19:15,760 --> 01:19:16,760
CONTROL THE CHARACTERISTIC

1804
01:19:16,760 --> 01:19:18,560
PHENOTYPE OF CELLS AS THEY GO

1805
01:19:18,560 --> 01:19:19,800
THROUGH THE DIFFERENTIATION

1806
01:19:19,800 --> 01:19:22,160
PROCESS. HE CONCLUDED THE

1807
01:19:22,160 --> 01:19:24,720
ISOLATION MITOTIC EXPANSION AND

1808
01:19:24,720 --> 01:19:26,720
SITE DIRECTED DELIVERY OF

1809
01:19:26,720 --> 01:19:28,400
AUTOLOGOUS STEM CELLS CAN GOVERN

1810
01:19:28,400 --> 01:19:30,680
THE RAPID AND SPECIFIC REPAIR OF

1811
01:19:30,680 --> 01:19:33,760
SKELETAL TISSUES.  26 YEARS

1812
01:19:33,760 --> 01:19:35,320
LATER, WE RECOGNIZE REVISED

1813
01:19:35,320 --> 01:19:36,760
CONCEPT AS FAR AS WHAT IS STEM

1814
01:19:36,760 --> 01:19:38,760
CELL, BECAME EVIDENT THAT

1815
01:19:38,760 --> 01:19:41,320
BIOLOGIC EFFECT OF EXOGENOUS

1816
01:19:41,320 --> 01:19:42,480
CELLS CAN BE DUE TO PRODUCTION

1817
01:19:42,480 --> 01:19:44,320
OF ANTI-INFLAMMATORY AND IMMUNE

1818
01:19:44,320 --> 01:19:46,880
MODULATING MEDIATORS, PROBABLY

1819
01:19:46,880 --> 01:19:49,400
MODIFY LOCAL ENVIRONMENT, AFFECT

1820
01:19:49,400 --> 01:19:52,160
LOCAL RESIDENT CELLS. THIS IS A

1821
01:19:52,160 --> 01:19:54,720
QUOTE FROM CAPLAN I URGE WE

1822
01:19:54,720 --> 01:19:56,920
CHANGE THE NAME TO MEDICINAL

1823
01:19:56,920 --> 01:19:58,200
SIGNALING CELLS TO ACTIVELY

1824
01:19:58,200 --> 01:19:59,720
REFLECT THE FACT THESE CELLS

1825
01:19:59,720 --> 01:20:01,920
HOME IN ON SITES OF INJURY, AND

1826
01:20:01,920 --> 01:20:05,240
THEY SECRETE BIOACTIVE FACTORS

1827
01:20:05,240 --> 01:20:07,600
THAT BOTH HAVE IMMUNE MODULATING

1828
01:20:07,600 --> 01:20:08,560
PROPERTIES, POTENTIALLY

1829
01:20:08,560 --> 01:20:12,040
REGENERATIVE. HE QUOTED FURTHER

1830
01:20:12,040 --> 01:20:13,920
INDEED PATIENT OWN SITE SPECIFIC

1831
01:20:13,920 --> 01:20:15,360
TISSUE SPECIFIC RESIDENT STEM

1832
01:20:15,360 --> 01:20:17,120
CELLS CONSTRUCTED NEW TISSUE

1833
01:20:17,120 --> 01:20:18,360
STIMULATED BY THESE BIOACTIVE

1834
01:20:18,360 --> 01:20:20,680
FACTORS.  WE RECOGNIZE EXOGENOUS

1835
01:20:20,680 --> 01:20:22,360
CELLS MAY FUNCTION BY MODIFYING

1836
01:20:22,360 --> 01:20:23,800
THE INJURY ENVIRONMENT, RATHER

1837
01:20:23,800 --> 01:20:25,240
THAN DIRECTLY CONTRIBUTING TO

1838
01:20:25,240 --> 01:20:27,600
HEALING. SO AT THE END OF THE

1839
01:20:27,600 --> 01:20:29,520
DAY, THIS INTRODUCE CONCEPT OF

1840
01:20:29,520 --> 01:20:31,760
STIMULATION OF EXTRINSIC THE

1841
01:20:31,760 --> 01:20:32,920
INTRINSIC STEM CELL NICHE THAT

1842
01:20:32,920 --> 01:20:34,840
EXISTS AND MAKE TISSUES

1843
01:20:34,840 --> 01:20:35,760
PRE-NATAL AS WE GO THROUGH THE

1844
01:20:35,760 --> 01:20:38,440
TALK WE UNDERSTAND HOW EXOGENOUS

1845
01:20:38,440 --> 01:20:40,880
CELLS WE CAN USE HOW THEY

1846
01:20:40,880 --> 01:20:42,880
INTERACT WITH INTRINSIC STEM

1847
01:20:42,880 --> 01:20:46,280
CELL NICHE RESIDENT TISSU TISSUR

1848
01:20:46,280 --> 01:20:48,720
TALK LATER ON EXOSOMES EXOSOMESL

1849
01:20:48,720 --> 01:20:49,920
SKIP THIS IN THE INTEREST OF

1850
01:20:49,920 --> 01:20:51,760
TIME, DANIEL WILL TALK ABOUT

1851
01:20:51,760 --> 01:20:53,280
EXOSOMES BUT THESE EXTRA

1852
01:20:53,280 --> 01:20:56,240
CELLULAR VESICALES RELEASE CELL

1853
01:20:56,240 --> 01:20:58,120
CARTILAGE IF YOU WILL AND

1854
01:20:58,120 --> 01:21:00,560
PRESENT POTENTIAL TO OBTAIN

1855
01:21:00,560 --> 01:21:02,240
BENEFITS OF CELL THERAPY WITHOUT

1856
01:21:02,240 --> 01:21:05,960
CELL CULTURING AND EXOSOMES ARE

1857
01:21:05,960 --> 01:21:07,960
COMPLEX, ONE OF THE FUNDAMENTAL

1858
01:21:07,960 --> 01:21:09,720
MECHANISMS IS INDUCTION OF

1859
01:21:09,720 --> 01:21:11,400
POLARIZATION TO MACROPHAGES

1860
01:21:11,400 --> 01:21:13,720
CONTRIBUTING TO

1861
01:21:13,720 --> 01:21:14,400
ANTI-INFLAMMATORY IMMUNE

1862
01:21:14,400 --> 01:21:17,080
MODULATING PROPERTIES OF CELLS. 

1863
01:21:17,080 --> 01:21:18,840
CELLS WE CAN USE TODAY EXOGENOUS

1864
01:21:18,840 --> 01:21:22,120
CELLS MARROW ADIPOSE PERINATAL

1865
01:21:22,120 --> 01:21:24,080
TISSUE AND AGAIN INTRINSIC STEM

1866
01:21:24,080 --> 01:21:25,280
CELL NICHE. WE WILL COME BACK TO

1867
01:21:25,280 --> 01:21:29,080
THIS AS WE GO THROUGH THIS. WE

1868
01:21:29,080 --> 01:21:32,800
TALK ABOUT CELLS MSCs, THE S

1869
01:21:32,800 --> 01:21:35,000
IS STROMAL CELLS. MESS CHIMAL

1870
01:21:35,000 --> 01:21:37,320
STROMAL CELLS AND STANDARD

1871
01:21:37,320 --> 01:21:44,640
CRITERIA PUT FORTH BY

1872
01:21:44,640 --> 01:21:46,760
INTERNATIONAL SOCIETY FOR

1873
01:21:46,760 --> 01:21:49,200
PLASTIC GENE THERAPY, AND

1874
01:21:49,200 --> 01:21:50,520
DIFFERENTIATION CAPACITY SO KEEP

1875
01:21:50,520 --> 01:21:54,080
THIS IN MINE. THIS IS BASIC

1876
01:21:54,080 --> 01:21:55,480
DEFINITION AND THIS IS

1877
01:21:55,480 --> 01:21:57,120
IMPORTANTLY BASED ON CELL

1878
01:21:57,120 --> 01:22:02,000
BEHAVIOR IN VITRO. IN CULTURE. 

1879
01:22:02,000 --> 01:22:03,840
GEORGE MADE SOME VERY IMPORTANT

1880
01:22:03,840 --> 01:22:05,360
CONTRIBUTIONS IN THIS FIELD AND

1881
01:22:05,360 --> 01:22:06,960
INTRODUCED CONCEPT CONNECTIVE

1882
01:22:06,960 --> 01:22:08,520
TISSUE PROGENITOR, PROBABLY A

1883
01:22:08,520 --> 01:22:10,320
BETTER TERM TO USE, WITH CELLS

1884
01:22:10,320 --> 01:22:13,640
WE ARE IMPLANTING IN OUR

1885
01:22:13,640 --> 01:22:16,000
CLINICAL APPLICATION

1886
01:22:16,000 --> 01:22:17,040
HETEROGENOUS POPULATION OF

1887
01:22:17,040 --> 01:22:19,800
TISSUE RESIDENT CELLS AND CAN

1888
01:22:19,800 --> 01:22:21,680
PROLIFERATE AND GENERATE PROGENY

1889
01:22:21,680 --> 01:22:23,760
WITH CAPACITY TO DIFFERENTIATE

1890
01:22:23,760 --> 01:22:25,880
IN ONE OR MORE -- DIFFERENTIATE

1891
01:22:25,880 --> 01:22:27,400
TO CONNECTIVE TISSUES, WE CAN

1892
01:22:27,400 --> 01:22:29,320
MEASURE PROGENITOR CELLS BY

1893
01:22:29,320 --> 01:22:31,840
COUNTING COLONY FORMING UNITS IN

1894
01:22:31,840 --> 01:22:34,160
CULTURE, EACH REGENERATIVE CELL

1895
01:22:34,160 --> 01:22:36,520
IN CELL FOR COLONY. I WOULD

1896
01:22:36,520 --> 01:22:38,120
SUBMIT THE TERM MSC SHOULD BE

1897
01:22:38,120 --> 01:22:40,120
USED TO REFER TO CULTURE

1898
01:22:40,120 --> 01:22:42,640
EXPANDED POPULATION OF CELLS

1899
01:22:42,640 --> 01:22:45,840
THAT MEET THESE CRITERIA,

1900
01:22:45,840 --> 01:22:47,320
IMAGING FOR CELL THERAPY AND

1901
01:22:47,320 --> 01:22:48,920
SHOULDN'T USE THE TERM TO

1902
01:22:48,920 --> 01:22:50,040
DESCRIBE HETEROGENOUS

1903
01:22:50,040 --> 01:22:51,840
POPULATIONS OF NATIVE CELLS WITH

1904
01:22:51,840 --> 01:22:54,040
UNDEFINED PROPERTIES IN VIVO.

1905
01:22:54,040 --> 01:22:55,480
THIS GETS SOME OF THE POINTS

1906
01:22:55,480 --> 01:22:56,880
LAST DISCUSSION FROM CONNIE'S

1907
01:22:56,880 --> 01:22:59,280
TALK, THE HETEROGENEITY IN

1908
01:22:59,280 --> 01:23:00,120
FORMULATIONS AND NEED TO

1909
01:23:00,120 --> 01:23:01,160
CHARACTERIZE WHAT WE ARE PUTTING

1910
01:23:01,160 --> 01:23:03,800
TO OUR PATIENTS.  HOW MIGHT

1911
01:23:03,800 --> 01:23:05,920
CELLS WORK? SEEM TORR SYMPTOM

1912
01:23:05,920 --> 01:23:08,160
MODIFYING AS FAR AS IMPROVING

1913
01:23:08,160 --> 01:23:09,080
SYMPTOMS TYPICALLY PAIN AND

1914
01:23:09,080 --> 01:23:12,280
SWELLING IN PATIENTS. AGAIN BACK

1915
01:23:12,280 --> 01:23:15,240
TO PARACRINE MECHANISM VIA

1916
01:23:15,240 --> 01:23:16,400
ANTI-INFLAMMATORY MEDIATORS AND

1917
01:23:16,400 --> 01:23:18,720
VARIOUS IMMUNE MODULATING

1918
01:23:18,720 --> 01:23:20,800
FACTORS. THEY WAY ACT ON

1919
01:23:20,800 --> 01:23:23,320
SYNOVIAL CELLS IN THE JOINT FOR

1920
01:23:23,320 --> 01:23:24,960
IMMUNOMODULATION AND SYMPTOM

1921
01:23:24,960 --> 01:23:26,840
MODIFICATION. THINK OF

1922
01:23:26,840 --> 01:23:28,080
OSTEOARTHRITIS. OTHER PART OF

1923
01:23:28,080 --> 01:23:29,720
THIS IS CAN CELLS STRUCTURE

1924
01:23:29,720 --> 01:23:32,200
MODIFYING? CAN THEY INDUCE TRUE

1925
01:23:32,200 --> 01:23:34,840
TISSUE GENERATION. TO THAT THEY

1926
01:23:34,840 --> 01:23:37,160
NEED TO ACT UPON CHONDROCYTE IN

1927
01:23:37,160 --> 01:23:40,040
JOINT, SYNOVIAL CELLS, BOB

1928
01:23:40,040 --> 01:23:41,000
MARROW BEREAVED CELLS TO INDUCE

1929
01:23:41,000 --> 01:23:43,040
-- BONE MARROW DERIVED CELLS TO

1930
01:23:43,040 --> 01:23:44,560
INDUCE TISSUE REGENERATION. THIS

1931
01:23:44,560 --> 01:23:46,040
IS A PIE IN THE SKY AS FAR AS

1932
01:23:46,040 --> 01:23:48,680
USING CELL THERAPIES TO INDUCE

1933
01:23:48,680 --> 01:23:52,040
TWO STRUCTURE MODIFICATION. WITH

1934
01:23:52,040 --> 01:23:54,120
THAT BACKGROUND ABOUT CELL

1935
01:23:54,120 --> 01:23:55,240
THERAPY WE CAN CONSIDER THE ROLE

1936
01:23:55,240 --> 01:23:58,320
IN TREATMENT OF OSTEOARTHRITIS.

1937
01:23:58,320 --> 01:23:59,800
INFLAMMATION PLAY AS CRITICAL

1938
01:23:59,800 --> 01:24:01,200
ROLE IN PATHOPHYSIOLOGY OF

1939
01:24:01,200 --> 01:24:03,880
OSTEOARTHRITIS. THIS IS A GROUP

1940
01:24:03,880 --> 01:24:05,480
ON THIS DOPE NEED TO GET INTO

1941
01:24:05,480 --> 01:24:07,080
DETAIL BUT IMPORTANT TO POINT

1942
01:24:07,080 --> 01:24:09,160
OUT OA IS COMPLEX PROCESS

1943
01:24:09,160 --> 01:24:10,760
CHARACTERIZED BY INVOLVEMENT OF

1944
01:24:10,760 --> 01:24:13,160
COURSE IN NUMEROUS CELLS AND

1945
01:24:13,160 --> 01:24:18,040
TISSUES, CARTILAGE SUBCHONDRAL

1946
01:24:18,040 --> 01:24:19,640
BONE, SYNOVIUM. WE KNOW INNATE

1947
01:24:19,640 --> 01:24:23,040
IMMUNE CELLS, MACROPHAGES MK

1948
01:24:23,040 --> 01:24:24,800
CELLS PLAY IMPORTANT ROLE IN

1949
01:24:24,800 --> 01:24:26,920
EARLY INFLAMMATORY RESPONSE AND

1950
01:24:26,920 --> 01:24:28,560
ADAPTIVE IMMUNE CELLS, T AND B

1951
01:24:28,560 --> 01:24:30,000
CELLS CONTRIBUTE TO DEVELOPMENT

1952
01:24:30,000 --> 01:24:34,120
OF CHRONIC RELAPSING SYMPTOMS IN

1953
01:24:34,120 --> 01:24:37,160
OUR PATIENTS. OBVIOUSLY

1954
01:24:37,160 --> 01:24:41,960
INFLAMMATION I IS A HIGHLY COMPX

1955
01:24:41,960 --> 01:24:43,400
PROCESS. ANTI-INFLAMMATORY AND

1956
01:24:43,400 --> 01:24:44,720
IMMUNE MODULATING EFFECTS OF

1957
01:24:44,720 --> 01:24:48,840
CELLS IS CONTEXT DEPENDENT. THE

1958
01:24:48,840 --> 01:24:51,720
DIAGRAM GIVES A SENSE, MSCs,

1959
01:24:51,720 --> 01:24:52,560
MESENCHYMAL STROMAL CELLS FROM

1960
01:24:52,560 --> 01:24:54,120
MARROW OR ADIPOSE TISSUE,

1961
01:24:54,120 --> 01:24:57,480
STANDARD SOURCES, THESE CAN

1962
01:24:57,480 --> 01:24:58,400
PROMOTE ENDPLAYMATION WHEN

1963
01:24:58,400 --> 01:24:59,440
IMMUNE SEASONAL IS

1964
01:24:59,440 --> 01:25:03,240
UNDERACTIVATED. MSCs DECREASE

1965
01:25:03,240 --> 01:25:05,640
INFLAMMATION WHEN IMMUNE SYSTEM

1966
01:25:05,640 --> 01:25:08,080
IS OVERACTIVATED. SUPPRESS

1967
01:25:08,080 --> 01:25:10,760
IMMUNE SUPPRESSERS THAT SWITCH

1968
01:25:10,760 --> 01:25:13,280
FROM PRO INFLAMMATORY TO

1969
01:25:13,280 --> 01:25:15,760
ANTI-INFLAMMATORY PHENOTYPES,

1970
01:25:15,760 --> 01:25:18,880
HOW COMPLEX THESE CELLS ARE.

1971
01:25:18,880 --> 01:25:21,040
THEY ARE MEDIATED BY

1972
01:25:21,040 --> 01:25:23,200
POLARIZATION OF PROINFLAMMATORY

1973
01:25:23,200 --> 01:25:23,840
M 1 TO PANT INFLAMMATORY

1974
01:25:23,840 --> 01:25:27,000
PHENOTYPE. SO SUMMARIZED A LOT

1975
01:25:27,000 --> 01:25:28,560
OF WORK IN INTEREST OF TIME,

1976
01:25:28,560 --> 01:25:31,800
CLEARLY THE CELL THERAPIES

1977
01:25:31,800 --> 01:25:32,400
MODULATE INFORMATION AND

1978
01:25:32,400 --> 01:25:33,560
UNDERSTANDING IS THESE THERAPIES

1979
01:25:33,560 --> 01:25:37,200
WORK VIA PRODUCTION OF HOST OF

1980
01:25:37,200 --> 01:25:38,200
ANTI-INFLAMMATORY AND IMMUNE

1981
01:25:38,200 --> 01:25:40,440
MODULATING FACTORS AND BIOLOGY

1982
01:25:40,440 --> 01:25:41,720
IS COMPLEX, ILLUSTRATED HERE,

1983
01:25:41,720 --> 01:25:43,880
JUST GIVE YOU A 30,000-FOOT

1984
01:25:43,880 --> 01:25:45,360
VIEW. I WANT TO INTRODUCE THE

1985
01:25:45,360 --> 01:25:47,800
CONCEPT THESE IMPORTANT

1986
01:25:47,800 --> 01:25:50,520
INTERACTIONS BETWEEN MSCs AND

1987
01:25:50,520 --> 01:25:51,720
IMMUNE CELLS SUBTYPES WHETHER

1988
01:25:51,720 --> 01:25:55,120
SYSTEMIC OR LOCAL IMMUNE CELLS

1989
01:25:55,120 --> 01:25:57,600
IN THE JOINT ENVIRONMENT. WE

1990
01:25:57,600 --> 01:26:00,440
KNOW MCs CAN DIRECTLY AFFECT

1991
01:26:00,440 --> 01:26:02,240
SYNOVIAL INFLAMMATION. THIS IS

1992
01:26:02,240 --> 01:26:04,040
WORK FROM A GROUP IN NETHERLANDS

1993
01:26:04,040 --> 01:26:05,400
USING MOUSE MODEL OF

1994
01:26:05,400 --> 01:26:08,960
EXPERIMENTAL OA. INDUCED SIGH

1995
01:26:08,960 --> 01:26:12,240
EWE VIETIS OR DISSEMINATION OF

1996
01:26:12,240 --> 01:26:15,480
MEANIAL ME IN THIS CUSS MODEL.

1997
01:26:15,480 --> 01:26:18,680
THEY FIND SYNOVIUM IN ANIMALS.

1998
01:26:18,680 --> 01:26:22,320
IF THEY TREAT THE ANIMALS, TREAT

1999
01:26:22,320 --> 01:26:24,960
WITH ADIPOSE DERIVED CELLS, THEY

2000
01:26:24,960 --> 01:26:26,960
FOUND SUPPRESSION OF ACTIVATED

2001
01:26:26,960 --> 01:26:27,840
MACROPHAGES, THEY SEE DOWN

2002
01:26:27,840 --> 01:26:29,800
REGULATION OF VARIOUS

2003
01:26:29,800 --> 01:26:33,400
PROINFLAMMATORY MEDIATORS.

2004
01:26:33,400 --> 01:26:35,080
DECREASE IN OSTEOCYTE FORMATION.

2005
01:26:35,080 --> 01:26:39,000
YOU CAN SEE PROACTIVELY SYNOVIAL

2006
01:26:39,000 --> 01:26:41,200
ACTIVATION SIGH KNEW VIETIS

2007
01:26:41,200 --> 01:26:42,880
SCORES IN THESE ANIMALS SO BASIC

2008
01:26:42,880 --> 01:26:44,560
LABORATORY ANIMALS DO

2009
01:26:44,560 --> 01:26:47,280
DEMONSTRATE DIRECT EFFECT OF MSC

2010
01:26:47,280 --> 01:26:48,880
ON THAT SYNOVIAL INFLAMMATORY

2011
01:26:48,880 --> 01:26:56,200
PROCESS.  MORE WORK AT MSC AND

2012
01:26:56,200 --> 01:26:58,680
HOW MEDIATED BY CELLS IN INNATE

2013
01:26:58,680 --> 01:27:00,560
IMMUNE SYSTEM, IMPORTANT FROM

2014
01:27:00,560 --> 01:27:02,160
GROUP IN ROT TEARDAM. THEY

2015
01:27:02,160 --> 01:27:04,960
REPORT SYSTEMICALLY ADMINISTERED

2016
01:27:04,960 --> 01:27:07,280
MSCs ARE PHAGOSIGH THOSED BY

2017
01:27:07,280 --> 01:27:11,560
MONOCYTES THAT LEADS TO POLAR --

2018
01:27:11,560 --> 01:27:14,320
PHAGOCYTOSED BY THIS PHENOTYPIC

2019
01:27:14,320 --> 01:27:17,240
SWITCH. THESE PRIME MONOCYTES

2020
01:27:17,240 --> 01:27:18,640
INDUCE UPREGULATION OF T

2021
01:27:18,640 --> 01:27:20,080
REGULATORY CELLS TO YOUR

2022
01:27:20,080 --> 01:27:21,080
ADAPTIVE IMMUNE RESPONSE, LEADS

2023
01:27:21,080 --> 01:27:23,000
TO INDUCTION OF LONG TERM

2024
01:27:23,000 --> 01:27:24,640
ADAPTIVE IMMUNE RESPONSE UPON

2025
01:27:24,640 --> 01:27:25,680
DIFFERENTIATION OF THESE

2026
01:27:25,680 --> 01:27:28,000
AFFECTED MONOCYTESES AFTER THEY

2027
01:27:28,000 --> 01:27:29,280
PHAGOCYTOSE CELLS, DIFFERENTIATE

2028
01:27:29,280 --> 01:27:31,560
IN IMMUNE MACROPHAGES.  THIS IS

2029
01:27:31,560 --> 01:27:33,720
INTERESTING BECAUSE THE DATA

2030
01:27:33,720 --> 01:27:35,080
SUGGESTS THE BIOLOGICAL ACTIVITY

2031
01:27:35,080 --> 01:27:36,720
OF INFUSED CELL MAYBE

2032
01:27:36,720 --> 01:27:37,800
INDEPENDENT OF CELLULAR

2033
01:27:37,800 --> 01:27:39,760
ACTIVITY. CHALLENGES HYPOTHESIS

2034
01:27:39,760 --> 01:27:41,520
THAT AFFECTS OF MSCs ARE

2035
01:27:41,520 --> 01:27:44,280
MEDIATED BY THE SECRETOME. THE

2036
01:27:44,280 --> 01:27:47,200
ADDITIONAL SIGNALING CELL FROM

2037
01:27:47,200 --> 01:27:49,040
CAPLAN YEARS AGO SO IMPORTANT

2038
01:27:49,040 --> 01:27:50,640
REARE ACTION BETWEEN CELLS

2039
01:27:50,640 --> 01:27:54,360
MSCs AND IMMUNE CELLS WHICH

2040
01:27:54,360 --> 01:27:55,400
LEADS TO DISCUSS MORE ABOUT THE

2041
01:27:55,400 --> 01:27:57,600
ROLE OF MACROPHAGES IN OA

2042
01:27:57,600 --> 01:27:59,360
DEVELOPMENT AND PROGRESSION,

2043
01:27:59,360 --> 01:28:05,040
GROUP FROM FRANCE WITH

2044
01:28:05,040 --> 01:28:06,600
CHRISTIAN, THEY IMPORTANT POINT

2045
01:28:06,600 --> 01:28:09,600
OUT HOW MACROPHAGES ARE

2046
01:28:09,600 --> 01:28:13,400
IMPORTANT INFILTRATES IN OA. BUT

2047
01:28:13,400 --> 01:28:15,800
MACRO BIOLOGY IS COMPLEX. PEOPLE

2048
01:28:15,800 --> 01:28:17,480
DISCUSS TWO POPULATION

2049
01:28:17,480 --> 01:28:19,040
MACROPHAGES RESIDENT

2050
01:28:19,040 --> 01:28:19,760
MACROPHAGES, PRESENT IN THE

2051
01:28:19,760 --> 01:28:21,640
JOINT, AS WELL AS MONOCYTE

2052
01:28:21,640 --> 01:28:22,880
DERIVED MACROPHAGES FROM

2053
01:28:22,880 --> 01:28:25,840
CIRCULATION IN THE INTERACTION

2054
01:28:25,840 --> 01:28:27,680
BETWEEN THESE POPULATIONS IS

2055
01:28:27,680 --> 01:28:28,840
CRITICALLY IMPORTANT. MACROPHAGE

2056
01:28:28,840 --> 01:28:30,200
BIOLOGY IS VERY COMPLEX WITH

2057
01:28:30,200 --> 01:28:33,520
THESE CELLS INFILTRATING ANA

2058
01:28:33,520 --> 01:28:37,080
BOLLIC AND CATABOLIC, THERE ARE

2059
01:28:37,080 --> 01:28:39,640
PRO INTORY AND ANTI-INFLAMMATORY

2060
01:28:39,640 --> 01:28:41,440
MACROPHAGES IN OA SO FOLLOWING

2061
01:28:41,440 --> 01:28:43,520
THE THEME ABOUT MACROPHAGES,

2062
01:28:43,520 --> 01:28:45,960
OTHER WORK HERE THAT THEY WENT

2063
01:28:45,960 --> 01:28:47,760
ON THE SAME GROUP FROM FRANCE,

2064
01:28:47,760 --> 01:28:50,600
JUST TO SUMMARIZE THE PATHWAYS

2065
01:28:50,600 --> 01:28:52,600
DISCUSSED.  THERE IS

2066
01:28:52,600 --> 01:28:54,080
INFLAMMATORY SIGNALING PATHWAYS

2067
01:28:54,080 --> 01:28:54,720
ACTIVATED IN SETTING OF

2068
01:28:54,720 --> 01:28:57,800
OSTEOARTHRITIS. AND THAT DOES

2069
01:28:57,800 --> 01:28:59,840
ATTRACT CIRCULATING

2070
01:28:59,840 --> 01:29:01,360
PROINFLAMMATORY MONOCYTE DERIVED

2071
01:29:01,360 --> 01:29:04,040
MACROPHAGE, THE M 1 POPULATION

2072
01:29:04,040 --> 01:29:05,480
WHICH THEN WILL INFILTRATE THE

2073
01:29:05,480 --> 01:29:07,520
JOINT, THESE PROINFLAMMATORY

2074
01:29:07,520 --> 01:29:10,040
MACROPHAGES DO CARRY OUT

2075
01:29:10,040 --> 01:29:11,160
PHAGOSITIC FUNCTION BUT THEN

2076
01:29:11,160 --> 01:29:12,640
BEGIN TO SECRETE

2077
01:29:12,640 --> 01:29:14,000
ANTI-INFLAMMATORY MEDIATORS.

2078
01:29:14,000 --> 01:29:16,320
WHICH CAN ULTIMATELY HAVE ROLE

2079
01:29:16,320 --> 01:29:18,960
PERHAPS IN PROMOTING WOUND

2080
01:29:18,960 --> 01:29:20,680
REPAIR. THIS LEADS POLARIZATION

2081
01:29:20,680 --> 01:29:23,080
FROM THIS M 1 PROINFLAMMATORY TO

2082
01:29:23,080 --> 01:29:25,880
THE ANTI-INFLAMMATORY PHENOTYPE.

2083
01:29:25,880 --> 01:29:29,480
FAILURE OF THIS ORCHESTRATED

2084
01:29:29,480 --> 01:29:30,840
MACROPHAGE RESPONSE FROM

2085
01:29:30,840 --> 01:29:33,320
SYNOVIAL MEMBRANE OR FAILURE OF

2086
01:29:33,320 --> 01:29:35,240
RESOLUTION LEADS TO CHRONIC

2087
01:29:35,240 --> 01:29:37,240
INFLAMMATION, CONTRIBUTING TO

2088
01:29:37,240 --> 01:29:38,560
PERSISTENT SYMPTOMS. WHAT ABOUT

2089
01:29:38,560 --> 01:29:41,320
USING MSDs TO TARGET THESE

2090
01:29:41,320 --> 01:29:42,760
MACROPHAGES? SINCE THEY HAVE

2091
01:29:42,760 --> 01:29:44,440
SUCH A CRITICALLY IMPORTANT ROLE

2092
01:29:44,440 --> 01:29:46,440
AND CLEARLY MSCs INTERACT WITH

2093
01:29:46,440 --> 01:29:49,760
IMMUNE CELLS, HOW CAN MSCs

2094
01:29:49,760 --> 01:29:51,720
HAVE THERAPEUTIC IN THE JOINT

2095
01:29:51,720 --> 01:29:55,320
HERE? SO AGAIN MSC ENABLE SWITCH

2096
01:29:55,320 --> 01:29:57,360
FROM PROINFLAMMATORY TO

2097
01:29:57,360 --> 01:30:01,960
ANTI-INFLAMMATORY SUB SETS.  

2098
01:30:01,960 --> 01:30:04,320
MOLECULAR MECHANISM ARE COMPLEX

2099
01:30:04,320 --> 01:30:06,680
BUT NUMEROUS FACTORS INCLUDING

2100
01:30:06,680 --> 01:30:10,600
TNF ALPHA, PBE 2, EXTRA CELLULAR

2101
01:30:10,600 --> 01:30:12,480
VESICLES PLAY A ROLE. SO WE HAVE

2102
01:30:12,480 --> 01:30:15,520
THE DAMAGE JOINT, AGAIN

2103
01:30:15,520 --> 01:30:17,080
PROINFLAMMATORY MACROPHAGES

2104
01:30:17,080 --> 01:30:19,280
INFILTRATE AND NOW MSCs ARE

2105
01:30:19,280 --> 01:30:21,360
SUPPLIED TO THAT PATIENT, DOSED

2106
01:30:21,360 --> 01:30:23,160
IN THE KNEE EXOGENOUSLY. THAT

2107
01:30:23,160 --> 01:30:24,720
CAN AFFECT THE MACROPHAGE

2108
01:30:24,720 --> 01:30:27,880
POPULATIONS AND POTENTIALLY LEAD

2109
01:30:27,880 --> 01:30:30,920
TO ANTI-INFLAMMATORY PHENOTYPE.

2110
01:30:30,920 --> 01:30:33,200
WE KNOW MSC DERIVED EXTRA

2111
01:30:33,200 --> 01:30:34,800
CELLULAR VESICALES TRANSPORT

2112
01:30:34,800 --> 01:30:36,000
MOLECULES, THAT CAN'T BE

2113
01:30:36,000 --> 01:30:38,080
SECRETED INCLUDING PROTEINS

2114
01:30:38,080 --> 01:30:39,880
ENZYMES, AND OTHER FACTORS, YOU

2115
01:30:39,880 --> 01:30:42,680
WILL HEAR MORE ABOUT THIS IN THE

2116
01:30:42,680 --> 01:30:45,000
TALK FROM DANIEL SARIS. MSC

2117
01:30:45,000 --> 01:30:46,760
DERIVED VESICALES ARE SHOWN TO

2118
01:30:46,760 --> 01:30:48,320
PROMOTE ANTI-INFLAMMATORY

2119
01:30:48,320 --> 01:30:52,880
MACROPHAGE PHENOTYPE, AN

2120
01:30:52,880 --> 01:30:53,760
IMPORTANT PRINCIPAL IN OUR

2121
01:30:53,760 --> 01:30:58,040
DISCUSSIONS LATER ON. SO THAT

2122
01:30:58,040 --> 01:31:00,160
BACKDROP, WHAT DOES THIS MEAN AS

2123
01:31:00,160 --> 01:31:02,600
TREATING OUR PATIENT?

2124
01:31:02,600 --> 01:31:04,240
THEY AFFECT QUALITY SYMPTOMS

2125
01:31:04,240 --> 01:31:06,280
FROM KNEE OA. 12 PATIENTS WITH

2126
01:31:06,280 --> 01:31:09,040
KNEE OA TREATED WITH SINGLE

2127
01:31:09,040 --> 01:31:10,440
INTRAARTICULAR INJECTION OF 1,

2128
01:31:10,440 --> 01:31:13,440
10, OR 50 MILLION BONE DERIVED

2129
01:31:13,440 --> 01:31:16,640
CELLS, NO ADVERSE EVENT, THEY

2130
01:31:16,640 --> 01:31:19,160
DID REPORT SIGNIFICANT

2131
01:31:19,160 --> 01:31:20,240
IMPROVEMENT IN OUTCOME MEASURES

2132
01:31:20,240 --> 01:31:22,200
YOU CAN SEE THE SYMPTOM SCALE ON

2133
01:31:22,200 --> 01:31:24,080
THE RIGHT SID SIDE. YOU DO SEE

2134
01:31:24,080 --> 01:31:27,200
IMPROVEMENT IN PATIENT SYMPTOMS

2135
01:31:27,200 --> 01:31:31,000
AND THEY HAVE THE MOST RELEVANT

2136
01:31:31,000 --> 01:31:33,120
IMPROVEMENTS IN OUTCOME

2137
01:31:33,120 --> 01:31:35,040
MEASURES. THIS GROUP WENT TO USE

2138
01:31:35,040 --> 01:31:37,360
MRI TO LOOK AT CARTILAGE

2139
01:31:37,360 --> 01:31:39,160
MORPHOLOGY AND COLLAGEN CONTENT

2140
01:31:39,160 --> 01:31:40,920
USING RELAXATION TIME

2141
01:31:40,920 --> 01:31:42,240
MEASUREMENTS.  THIS SCORE DIDN'T

2142
01:31:42,240 --> 01:31:45,040
CHANGE SO THOUGH SYMPTOM

2143
01:31:45,040 --> 01:31:45,840
MODIFYING MAYBE NOT STRUCTURE

2144
01:31:45,840 --> 01:31:48,040
MODIFYING IN JOINTS. THEY DID

2145
01:31:48,040 --> 01:31:51,120
FIND CARTILAGE CATABOLIC

2146
01:31:51,120 --> 01:31:54,760
BIOMARKER AND MRI SCORE LOWER

2147
01:31:54,760 --> 01:31:56,520
DOSE, SYNOVIAL SCORE IN THE

2148
01:31:56,520 --> 01:32:00,720
RIGHT, HIGH DOSE RED LINE, LOWER

2149
01:32:00,720 --> 01:32:04,040
SINUVITIS SCORE. THEY FIND

2150
01:32:04,040 --> 01:32:05,920
PROPORTION OF PRO-INFLAMMATORY

2151
01:32:05,920 --> 01:32:07,960
MONOCYTES AND MACROPHAGES

2152
01:32:07,960 --> 01:32:08,920
DECREASED IN H JOINTS TREAT WITH

2153
01:32:08,920 --> 01:32:12,640
MSC. THEY HAD A PANEL OF

2154
01:32:12,640 --> 01:32:13,880
ANTI-INFLAMMATORY MARKERS THEY

2155
01:32:13,880 --> 01:32:17,280
SURVEYED IN MSC SAMPLES, THEY

2156
01:32:17,280 --> 01:32:20,160
FOUND THIS PANEL WAS PREDICTIVE

2157
01:32:20,160 --> 01:32:22,000
OF PATIENT OUTCOME MEASURES OVER

2158
01:32:22,000 --> 01:32:24,560
12 MONTHS. THIS DATA PROVIDE

2159
01:32:24,560 --> 01:32:26,120
PREDICTIVE SELECTION CRITERIA WE

2160
01:32:26,120 --> 01:32:30,560
CAN USE IN STUDIES OF CELL

2161
01:32:30,560 --> 01:32:37,920
THERAPY IN PATIENTS.  IN

2162
01:32:37,920 --> 01:32:39,040
SYMPTOMATIC IMPROVEMENT, BRIEFLY

2163
01:32:39,040 --> 01:32:44,640
META ANALYSES, HERE IS ONE THAT

2164
01:32:44,640 --> 01:32:46,200
RANDOMIZED TRIALS RETROSPECTIVE

2165
01:32:46,200 --> 01:32:49,840
STUDIES OVER 500 PATIENTS REPORT

2166
01:32:49,840 --> 01:32:51,520
IMPROVEMENTS IN ANALOG SCORES,

2167
01:32:51,520 --> 01:32:55,480
NO ADVERSE EVENTS IN PATIENTS. 

2168
01:32:55,480 --> 01:32:58,480
META ANALYSIS, VISUAL

2169
01:32:58,480 --> 01:33:00,520
IMPROVEMENTS, YOU CAN SEE IN THE

2170
01:33:00,520 --> 01:33:02,320
FOREST PLOT HERE, THERE ARE

2171
01:33:02,320 --> 01:33:03,520
STUDIES THAT DEMONSTRATE

2172
01:33:03,520 --> 01:33:05,880
IMPROVEMENT WITH CELL THERAPY.

2173
01:33:05,880 --> 01:33:07,160
THE NEXT QUESTION, ARE THESE

2174
01:33:07,160 --> 01:33:08,640
CELLS STRUCTURE MODIFYING? CAN

2175
01:33:08,640 --> 01:33:13,040
WE REGENERATE TISSUE? LITERAL

2176
01:33:13,040 --> 01:33:14,040
STEM CELLS FOR PATIENT IS

2177
01:33:14,040 --> 01:33:15,400
POTENTIAL FOR REGENERATION OF

2178
01:33:15,400 --> 01:33:16,800
STRUCTURALLY FUNCTIONALLY NORMAL

2179
01:33:16,800 --> 01:33:20,040
TISSUE, BASED ON DEMONSTRATED

2180
01:33:20,040 --> 01:33:21,160
MULTI-LINEAGE DIFFERENTIATION

2181
01:33:21,160 --> 01:33:23,040
POTENTIAL CELLS WHICH IS SHOWN

2182
01:33:23,040 --> 01:33:27,040
IN VITRO. THERE IS LIMITED

2183
01:33:27,040 --> 01:33:28,320
EVIDENCE FOR TRUE TISSUE

2184
01:33:28,320 --> 01:33:29,680
REGENERATION BY IMPLANTED CELLS,

2185
01:33:29,680 --> 01:33:32,520
LIMITED BY NOW EXOGENOUS CELLS

2186
01:33:32,520 --> 01:33:37,080
WILL INT INTERCO-TO HOST TISSUED

2187
01:33:37,080 --> 01:33:37,760
DIFFERIATE TO HUMAN -- INTER

2188
01:33:37,760 --> 01:33:40,400
COLLATE TO HOST TISSUES. TO

2189
01:33:40,400 --> 01:33:41,360
UNDERSTAND REGENERATION WE NEED

2190
01:33:41,360 --> 01:33:43,960
TO KNOW IMPORTANT TO UNDERSTAND

2191
01:33:43,960 --> 01:33:46,920
HOW TISSUE GENERATION OCCURS. IT

2192
01:33:46,920 --> 01:33:50,200
IS FELT TISSUE GENERATION IN

2193
01:33:50,200 --> 01:33:52,680
ADULT MAMMALIAN TISSUE IN ORGANS

2194
01:33:52,680 --> 01:33:55,440
IS ORCHESTRATED BY IMMUNE

2195
01:33:55,440 --> 01:33:57,360
RESPONSE H COMPLEX BIOLOGY BUT

2196
01:33:57,360 --> 01:33:59,320
PLAY CRITICAL ROLE IN TISSUE

2197
01:33:59,320 --> 01:34:01,880
REGENERATION. NEUTROPHILS IN PRO

2198
01:34:01,880 --> 01:34:03,200
INFLAMMATORY MACROPHAGES

2199
01:34:03,200 --> 01:34:05,000
INFILTRATE THE JOINTS. WE HAVE

2200
01:34:05,000 --> 01:34:08,760
INJURED JOINT ARTHRITIC JOINT,

2201
01:34:08,760 --> 01:34:11,520
PTOA B JOINT, M 1 MA CASH FLOW

2202
01:34:11,520 --> 01:34:12,360
PHAGOINFILTRATE THE JOINT IN

2203
01:34:12,360 --> 01:34:23,600
RESPONSEOBTAINFLAMTORY MEDIATORH

2204
01:34:24,920 --> 01:34:26,400
POLARIZED PHENOTYPE BUT THE

2205
01:34:26,400 --> 01:34:28,880
PROLONGED DAMAGE CAN LEAD TO

2206
01:34:28,880 --> 01:34:29,840
UNRESOLVED INFLAMMATION THAT

2207
01:34:29,840 --> 01:34:31,680
LEADS TO FIBROSIS RATHER THAN

2208
01:34:31,680 --> 01:34:33,360
TRUE TISSUE REGENERATION.  THIS

2209
01:34:33,360 --> 01:34:34,840
IS IMPORTANT BIOLOGIC CHALLENGE

2210
01:34:34,840 --> 01:34:37,600
HERE. THIS GETS BACK TO THE

2211
01:34:37,600 --> 01:34:38,600
INTRINSIC STEM CELL NICHE, WE

2212
01:34:38,600 --> 01:34:40,160
ARE TALKING POTENTIAL TO

2213
01:34:40,160 --> 01:34:44,440
REGENERATE TISSUE. MANY HARBOR A

2214
01:34:44,440 --> 01:34:45,440
POPULATION OF INTRINSIC

2215
01:34:45,440 --> 01:34:46,960
REGENERATIVE CELLS, THESE ARE

2216
01:34:46,960 --> 01:34:51,960
LOCALIZED TO WALLS OF BLOOD

2217
01:34:51,960 --> 01:34:54,680
VESSELS, PICTURE BOTTOM RIGHT

2218
01:34:54,680 --> 01:34:57,880
IMPORTANT PAPER FROM BACK IN

2219
01:34:57,880 --> 01:35:00,360
2008, DEMONSTRATING THE PRESENCE

2220
01:35:00,360 --> 01:35:02,520
OF THESE CELLS. WE KNOW

2221
01:35:02,520 --> 01:35:04,000
EXOGENOUS CELLS PRODUCE

2222
01:35:04,000 --> 01:35:05,440
SIGNALING MOLECULES THAT

2223
01:35:05,440 --> 01:35:06,880
STIMULATE THESE INTRINSIC

2224
01:35:06,880 --> 01:35:08,200
PROGENITOR CELLS. THIS IS

2225
01:35:08,200 --> 01:35:11,320
PROBABLY THESE INTRINSIC CELLS

2226
01:35:11,320 --> 01:35:14,280
THAT INITIATE TISSUE HEALING AND

2227
01:35:14,280 --> 01:35:17,160
REGENERATION. SO POTENTIAL TO

2228
01:35:17,160 --> 01:35:18,520
INDUCE REGENERATION LIKELY DUE

2229
01:35:18,520 --> 01:35:20,400
TO STIMULATION OF INTRINSIC STEM

2230
01:35:20,400 --> 01:35:22,120
OR PROGENITOR CELLS THAT

2231
01:35:22,120 --> 01:35:23,880
RESIDENT IN MANY TISSUES USE THE

2232
01:35:23,880 --> 01:35:27,080
TERM CONNECTIVE TISSUE

2233
01:35:27,080 --> 01:35:31,160
REGENERATIVE BACK TO GEORGE

2234
01:35:31,160 --> 01:35:33,720
MUSCHLER'S WORK AS WELL. OUR

2235
01:35:33,720 --> 01:35:36,280
STUDY ANIMAL MODEL, POTENTIAL

2236
01:35:36,280 --> 01:35:37,400
FOR CELLS TO REGENERATE TISSUE

2237
01:35:37,400 --> 01:35:40,360
IN THE OA JOINT. THIS GROUP FROM

2238
01:35:40,360 --> 01:35:44,640
CHINA USE RAT KNEE OA MODEL. ACL

2239
01:35:44,640 --> 01:35:45,960
TRANSSECTION MODEL, ANIMALS

2240
01:35:45,960 --> 01:35:47,280
TREAT WITH BONE MARROW DERIVED

2241
01:35:47,280 --> 01:35:50,720
MANY,SC OR THE EXOSOMES AND

2242
01:35:50,720 --> 01:35:52,720
FOUND BONE MARROW DERIVED AN

2243
01:35:52,720 --> 01:35:54,800
EXOSOMES ALLEVIATED THE

2244
01:35:54,800 --> 01:35:56,040
CARTILAGE DESTRUCTION AND SOME

2245
01:35:56,040 --> 01:35:57,360
BONE REMODELING IN THIS RAT

2246
01:35:57,360 --> 01:36:00,760
MODEL. YOU CAN SEE OA SCORE

2247
01:36:00,760 --> 01:36:04,000
DIFFERENT IN THOSE ANIMALS WITH

2248
01:36:04,000 --> 01:36:06,960
EXOSOMES OR BONE MARROW DERIVED

2249
01:36:06,960 --> 01:36:08,640
CELLS. FOUND REDUCED JOINT

2250
01:36:08,640 --> 01:36:11,840
DAMAGE AND CHANGES IN SUB --

2251
01:36:11,840 --> 01:36:13,440
MICROCT TO MEASURE

2252
01:36:13,440 --> 01:36:14,040
MICROSTRUCTURAL PROPERTIES IN

2253
01:36:14,040 --> 01:36:17,040
BONE. SO THEY FELT THESE BONE

2254
01:36:17,040 --> 01:36:19,400
MARROW DERIVED CELLS OBSERVED

2255
01:36:19,400 --> 01:36:21,200
BENEFICIAL EFFECT BY REDUCING

2256
01:36:21,200 --> 01:36:25,960
CELL SENESCENCE AND APOPTOSIS OF

2257
01:36:25,960 --> 01:36:26,880
CHONDROCYTES.  SO IMPORTANT

2258
01:36:26,880 --> 01:36:28,960
DISCUSSION LATER TODAY. WE ARE

2259
01:36:28,960 --> 01:36:31,560
NOT HUMAN CLINICAL STUDIES, ANY

2260
01:36:31,560 --> 01:36:32,880
EVIDENCE CELLS STRUCTURE MODIFY,

2261
01:36:32,880 --> 01:36:35,400
THERE'S EARLY EVIDENCE, CHRIS IN

2262
01:36:35,400 --> 01:36:37,200
KOREA, GROUP OF PATIENTS TREATED

2263
01:36:37,200 --> 01:36:39,680
WITH INTERARTICULAR INJECTION OF

2264
01:36:39,680 --> 01:36:41,120
OUTGAS ADIPOSE DERIVED MSC SO

2265
01:36:41,120 --> 01:36:43,880
THEY OBTAINED CELLS AND CULTURE

2266
01:36:43,880 --> 01:36:45,680
THE CELLS, SO THIS IS IN KOREA,

2267
01:36:45,680 --> 01:36:47,040
THE CELLS REJECT AFTER THREE

2268
01:36:47,040 --> 01:36:49,800
WEEKS CULTURE, THEY EXTENSIVELY

2269
01:36:49,800 --> 01:36:51,960
TESTED CELLS FOR CELL NUMBER,

2270
01:36:51,960 --> 01:36:53,920
VIABILITY, PURITY, IDENTITY, SO

2271
01:36:53,920 --> 01:36:55,120
DO THE APPROPRIATE ANALYSES ON

2272
01:36:55,120 --> 01:36:57,120
THEIR CELLS, PRIOR TO

2273
01:36:57,120 --> 01:36:58,160
IMPLANTATION. STUDIES THREE

2274
01:36:58,160 --> 01:36:59,600
DOSES IN A SMALL GROUP OF

2275
01:36:59,600 --> 01:37:01,720
PATIENTS. THEY FOUND

2276
01:37:01,720 --> 01:37:02,880
IMPROVEMENTS IN THEIR PATIENT

2277
01:37:02,880 --> 01:37:04,640
OUTCOME MEASURE BUT IMPORTANTLY

2278
01:37:04,640 --> 01:37:07,400
REJECTED EVALUATION WITH MRI AND

2279
01:37:07,400 --> 01:37:09,000
ARTHROSCOPY DID FIND THE SIZE OF

2280
01:37:09,000 --> 01:37:10,680
CARTILAGE DEFECT DECREASED IN

2281
01:37:10,680 --> 01:37:13,000
THE VOLUME OF CARTILAGE

2282
01:37:13,000 --> 01:37:14,600
INCREASED IN THE COMPARTMENT

2283
01:37:14,600 --> 01:37:16,800
SEEN GRAPHICALLY HERE. THEY

2284
01:37:16,800 --> 01:37:19,240
FOUND BIOPSY GENERATED HIGHLIGHT

2285
01:37:19,240 --> 01:37:20,280
CARTILAGE EARLY EVIDENCE HERE

2286
01:37:20,280 --> 01:37:22,280
CULTURE EXPANDED CELLS MAY IN

2287
01:37:22,280 --> 01:37:25,280
FACT BE STRUCTURE MODIFYING.

2288
01:37:25,280 --> 01:37:26,920
SIMILAR STUDY FROM PAIN,

2289
01:37:26,920 --> 01:37:28,480
RANDOMIZE TRIAL ALLOGENEIC,

2290
01:37:28,480 --> 01:37:31,520
CULTURE EXPANDED MARROW CELLS,

2291
01:37:31,520 --> 01:37:33,000
INTRAARTICULAR INJECTION IN

2292
01:37:33,000 --> 01:37:35,520
JOINTS OF KNEE OA PATIENTS

2293
01:37:35,520 --> 01:37:36,920
CONTROLLED WITH HYALURONIC ACID

2294
01:37:36,920 --> 01:37:38,360
INJECTION. AND THE CELL TREATED

2295
01:37:38,360 --> 01:37:41,800
PATIENTS HAD IMPROVEMENTS IN

2296
01:37:41,800 --> 01:37:42,680
THEIR PATIENT OUTCOME MEASURE

2297
01:37:42,680 --> 01:37:44,880
BUT IMPORTANTLY ON MRI USING

2298
01:37:44,880 --> 01:37:46,640
RELAXATION TIME MEASUREMENTS OF

2299
01:37:46,640 --> 01:37:48,080
CARTILAGE FOUND IMPROVEMENT IN

2300
01:37:48,080 --> 01:37:49,800
CARTILAGE QUALITY AND THOSE

2301
01:37:49,800 --> 01:37:51,240
PATIENTS TREATED WITH CELLS.

2302
01:37:51,240 --> 01:37:54,160
CULTURE EXPANDED CELLS. SO

2303
01:37:54,160 --> 01:37:56,280
POTENTIAL FOR CELL TO INDUCE

2304
01:37:56,280 --> 01:37:58,560
TISSUE REGENERATION. SO TO

2305
01:37:58,560 --> 01:38:00,000
CONCLUDE, I WOULD SUBMIT WE

2306
01:38:00,000 --> 01:38:01,480
CURRENTLY HAVE LITTLE ABILITY TO

2307
01:38:01,480 --> 01:38:03,440
USE TRUE STEM CELLS DEFINED BY

2308
01:38:03,440 --> 01:38:06,920
ANY FORMAL CELLULAR OR MOLECULAR

2309
01:38:06,920 --> 01:38:10,760
CRITERIA. BUT THERE IS DATA TO

2310
01:38:10,760 --> 01:38:12,960
SUGGEST SYMPTOM MODIFICATION.

2311
01:38:12,960 --> 01:38:15,120
CELL THERAPY HOLDS POTENTIAL FOR

2312
01:38:15,120 --> 01:38:18,320
SYMPTOMS IN KNEE OA. THIS

2313
01:38:18,320 --> 01:38:20,200
PARACRINE AFFECT AFFECTING LOCAL

2314
01:38:20,200 --> 01:38:21,680
TISSUE MICROENVIRONMENT BY

2315
01:38:21,680 --> 01:38:22,960
PRODUCTION OF ANTI-INFLAMMATORY

2316
01:38:22,960 --> 01:38:26,200
AND IMMUNE MODULATING FACTORS,

2317
01:38:26,200 --> 01:38:27,960
CLEARLY ERR ACT WITH LOCAL AND

2318
01:38:27,960 --> 01:38:30,280
SYSTEMIC IMMUNE CELL SUBTYPES IN

2319
01:38:30,280 --> 01:38:33,400
KNEE OA JOINT. PLAY A CRITICAL

2320
01:38:33,400 --> 01:38:36,080
ROLE IN MACROPHAGE POLARIZATION.

2321
01:38:36,080 --> 01:38:37,800
THE OTHER SIDE OF THE COIN TO

2322
01:38:37,800 --> 01:38:39,640
ABILITY TO MODIFY STRUCTURE AND

2323
01:38:39,640 --> 01:38:40,680
REGENERATE TISSUE THERE'S

2324
01:38:40,680 --> 01:38:44,320
POTENTIAL. WHAT WE NEED IS MOVE

2325
01:38:44,320 --> 01:38:46,160
TO ABILITY TO PICK OUT CELL

2326
01:38:46,160 --> 01:38:47,800
SORTING TO ALLOW SELECTION OF

2327
01:38:47,800 --> 01:38:49,000
DESIRED CELL POPULATIONS,

2328
01:38:49,000 --> 01:38:50,680
FOLLOWED BY CULTURE EXPANSION OF

2329
01:38:50,680 --> 01:38:51,760
THOSE CELLS AND MAYBE

2330
01:38:51,760 --> 01:38:54,400
IMPORTANTLY ELIMINATION OF THE

2331
01:38:54,400 --> 01:38:56,440
UNDESIRED CELLS. THIS SUGGESTS

2332
01:38:56,440 --> 01:38:58,080
NIEDERHUBER TO IDENTIFY MARKERS

2333
01:38:58,080 --> 01:39:00,200
OF PURITY POTENCY AND BIOLOGIC

2334
01:39:00,200 --> 01:39:02,200
ACTIVITY SO WE CAN AFFECT

2335
01:39:02,200 --> 01:39:03,720
CHARACTERIZE AND SELECT OPTIMAL

2336
01:39:03,720 --> 01:39:06,600
CELL POPULATION. I RECOGNIZE

2337
01:39:06,600 --> 01:39:08,200
TISSUE REGENERATION MAY OCCUR

2338
01:39:08,200 --> 01:39:11,160
VIA STIMULATION OF INTRINSIC

2339
01:39:11,160 --> 01:39:12,520
PROGENITOR CELLS RESIDENT IN

2340
01:39:12,520 --> 01:39:13,520
TISSUE. I WILL STOP THERE. THANK

2341
01:39:13,520 --> 01:39:19,200
YOU.

2342
01:39:19,200 --> 01:39:23,560
>>THANK YOU, SCOTT. THIS
IS

2343
01:39:23,560 --> 01:39:25,760
OPEN FOR QUESTIONS. I HAVE A

2344
01:39:25,760 --> 01:39:29,280
QUICK QUESTION REGARDING -- SO

2345
01:39:29,280 --> 01:39:32,600
MANY ANIMAL STUDIES IN

2346
01:39:32,600 --> 01:39:34,960
PARTICULAR USE YOUNG ANIMALS.

2347
01:39:34,960 --> 01:39:37,920
ARE THERE STUDIES SHOWING

2348
01:39:37,920 --> 01:39:42,880
WHETHER MACROPHAGE POLARIZATION

2349
01:39:42,880 --> 01:39:44,600
AFFECTS FROM CELLS FROM OLDER

2350
01:39:44,600 --> 01:39:48,480
INDIVIDUALS OR INDIVIDUALS WITH

2351
01:39:48,480 --> 01:39:51,560
DISEASE STATES, DO THEY

2352
01:39:51,560 --> 01:39:53,360
SIMILARLY INDUCE M 2

2353
01:39:53,360 --> 01:39:53,680
POLARIZATION?

2354
01:39:53,680 --> 01:39:56,560
>>NOT SEEING MUCH, VERY
GOOD

2355
01:39:56,560 --> 01:39:58,880
QUESTION, IN THE ANIMAL STUDIES

2356
01:39:58,880 --> 01:40:03,440
LARGELY BEEN EXPERIMENTAL OA S

2357
01:40:03,440 --> 01:40:04,760
NEXTUVITIS, D, MANYM MOLDS LIKE

2358
01:40:04,760 --> 01:40:06,440
THAT WE NEED CLINICAL STUDIES IN

2359
01:40:06,440 --> 01:40:08,280
OUR PATIENTS AND THAT IS WHY IN

2360
01:40:08,280 --> 01:40:10,480
OUR CLINICAL STUDIES WE NEED TO

2361
01:40:10,480 --> 01:40:11,800
REALLY CHARACTERIZE PHENOTYPE OF

2362
01:40:11,800 --> 01:40:15,080
PATIENTS SO I DON'T -- HAVE NOT

2363
01:40:15,080 --> 01:40:16,480
SEEN MUCH EXAMINED THAT

2364
01:40:16,480 --> 01:40:19,080
IMPORTANT QUESTION.

2365
01:40:19,080 --> 01:40:23,280
>>SO DAN GRANDE.

2366
01:40:23,280 --> 01:40:30,400
>>APPRECIATE -- HI.
SCOTT,

2367
01:40:30,400 --> 01:40:32,000
APPRECIATE YOUR WONDERFUL TALK.

2368
01:40:32,000 --> 01:40:34,840
I WANTED TO YOU TO PERHAPS

2369
01:40:34,840 --> 01:40:39,160
FOLLOW-UP WITH RESPECT TO DO YOU

2370
01:40:39,160 --> 01:40:41,400
THINK THAT SOME OF THE STUDIES

2371
01:40:41,400 --> 01:40:43,680
ARE ALLO GENIC, SOME ARE

2372
01:40:43,680 --> 01:40:44,840
AUTOLOGOUS, WHAT ARE YOU THINK

2373
01:40:44,840 --> 01:40:48,120
IS THE DIFFERENCE, IS THERE AN

2374
01:40:48,120 --> 01:40:49,720
IMPORTANT DIFFERENCE BETWEEN

2375
01:40:49,720 --> 01:40:53,320
CULTURED MSCs VERSUS USING SAY

2376
01:40:53,320 --> 01:40:54,840
BMAP WHERE YOU HAVE THE

2377
01:40:54,840 --> 01:40:56,080
INTERACTION OF THE OTHER CELLS

2378
01:40:56,080 --> 01:40:59,280
AND THE CROSS SIGNALING, VERSUS

2379
01:40:59,280 --> 01:41:04,160
PURE COB CENTRATION OF CULTURED

2380
01:41:04,160 --> 01:41:04,760
MSCs?

2381
01:41:04,760 --> 01:41:09,040
>>HUGE DIFFERENCE. THE
POORLY

2382
01:41:09,040 --> 01:41:11,080
CHARACTERIZED NATIVE CELL

2383
01:41:11,080 --> 01:41:13,760
PREPARATION, WE USE WITH BONE

2384
01:41:13,760 --> 01:41:17,080
(INAUDIBLE) THESE UNCULTURED

2385
01:41:17,080 --> 01:41:19,760
CELLS, HETEROGENOUS POPULATIONS,

2386
01:41:19,760 --> 01:41:21,880
VERY VARIOUS POPULATION CULTURE

2387
01:41:21,880 --> 01:41:24,320
OF CELLS, CULTURE CERTAIN CELL

2388
01:41:24,320 --> 01:41:26,120
DOMINATE THE CULTURE SO THEY ARE

2389
01:41:26,120 --> 01:41:28,200
VERY DIFFERENT. SO ALLOGENEIC,

2390
01:41:28,200 --> 01:41:30,280
IF WE USE THAT PREPARATION IT

2391
01:41:30,280 --> 01:41:32,840
GIVES THE POTENTIAL TO

2392
01:41:32,840 --> 01:41:34,840
CHARACTERIZE THOSE CELLS

2393
01:41:34,840 --> 01:41:36,000
PRE-OPERATIVE SO WE HAVE SOME

2394
01:41:36,000 --> 01:41:36,760
IDEA OF THE PROFILE OF THOSE

2395
01:41:36,760 --> 01:41:40,400
CELLS. SO THOSE WILL BE VERY

2396
01:41:40,400 --> 01:41:41,520
DIFFERENT POPULATIONS AND IF WE

2397
01:41:41,520 --> 01:41:44,640
MOVE TO ALLOGENEIC CELL SOURCES

2398
01:41:44,640 --> 01:41:46,320
THEN WE CAN DO APPROPRIATE CELL

2399
01:41:46,320 --> 01:41:47,480
SORTING, CULTURE EXPANSION OF

2400
01:41:47,480 --> 01:41:50,120
THE DESIRED CELLS IN THOSE

2401
01:41:50,120 --> 01:41:51,360
PREPARATIONS.  THEY CHARACTERIZE

2402
01:41:51,360 --> 01:41:52,840
WHAT WE ARE PUTTING IN PATIENTS.

2403
01:41:52,840 --> 01:41:54,440
I SUBMIT TO ALL OF US CLINICIANS

2404
01:41:54,440 --> 01:41:56,440
IS USING ALL THESE THERAPIES,

2405
01:41:56,440 --> 01:42:00,520
WHETHER CELL THERAPY OR PRP

2406
01:42:00,520 --> 01:42:02,520
QUESTION, WE NEED AN ALLOQUAT OF

2407
01:42:02,520 --> 01:42:04,640
THAT MATERIAL AND CARRY OUT OUR

2408
01:42:04,640 --> 01:42:05,520
LABORATORY, WHATEVER TESTS WE

2409
01:42:05,520 --> 01:42:08,400
CAN DO TO CHARACTERIZE THE

2410
01:42:08,400 --> 01:42:09,840
PURITY, POTENCY, ACTIVE WHATEVER

2411
01:42:09,840 --> 01:42:15,560
IT IS, WE IDENTIFY THE SENTINEL

2412
01:42:15,560 --> 01:42:17,080
MARKERS THAT ARE PRACTICAL AND

2413
01:42:17,080 --> 01:42:18,960
CORRELATE PATIENT OUTCOMES. 

2414
01:42:18,960 --> 01:42:20,440
CLINICAL OUTCOMES IMAGING

2415
01:42:20,440 --> 01:42:21,240
OUTCOMES WITH OUR CELL

2416
01:42:21,240 --> 01:42:23,880
CHARACTERIZATION. 

2417
01:42:23,880 --> 01:42:26,880
>>THANK YOU.

2418
01:42:26,880 --> 01:42:29,320
>>PAM ROBEY HAS A
QUESTION.

2419
01:42:29,320 --> 01:42:31,360
>>THANK YOU FOR THAT
OVERVIEW,

2420
01:42:31,360 --> 01:42:33,120
SUCH A WONDERFUL OVERVIEW. THIS

2421
01:42:33,120 --> 01:42:37,240
IS MORE OF A QUESTION GENERALLY

2422
01:42:37,240 --> 01:42:40,720
TO THE FIELD. THAT IS, DON'T YOU

2423
01:42:40,720 --> 01:42:43,000
THINK IT IS TIME TO ACTUALLY

2424
01:42:43,000 --> 01:42:46,800
START USING NAMES THAT ARE MORE

2425
01:42:46,800 --> 01:42:47,600
DEFINED IN MANY THE CELL

2426
01:42:47,600 --> 01:42:51,240
POPULATIONS WE ARE USING? YOU

2427
01:42:51,240 --> 01:42:53,360
REVIEWED NICELY THE HISTORY

2428
01:42:53,360 --> 01:42:55,800
BLIND THE TERM MESENCHYMAL STEM

2429
01:42:55,800 --> 01:42:56,840
CELL, I THINK GIVEN THE FACT

2430
01:42:56,840 --> 01:43:00,240
THAT WE NOW KNOW THAT THINGS

2431
01:43:00,240 --> 01:43:02,720
TOSSED TO THAT BUCKET ARE QUITE

2432
01:43:02,720 --> 01:43:08,400
DIFFERENT, THAT WE NEED TO START

2433
01:43:08,400 --> 01:43:09,960
GIVING CELLS SPECIFIC NAMES,

2434
01:43:09,960 --> 01:43:12,600
BONE MARROW DERIVED ADIPOSE

2435
01:43:12,600 --> 01:43:14,280
DERIVED.  THERE'S MANY TIMES

2436
01:43:14,280 --> 01:43:17,240
PEOPLE DON'T IDENTIFY THEIR CELL

2437
01:43:17,240 --> 01:43:20,120
SOURCE. WE KNOW THESE CELLS ARE

2438
01:43:20,120 --> 01:43:21,360
INTRINSICALLY DIFFERENT. THIS IS

2439
01:43:21,360 --> 01:43:24,520
VERY IMPORTANT IN TERMS OF

2440
01:43:24,520 --> 01:43:25,960
CLINICAL APPLICATION, THAT

2441
01:43:25,960 --> 01:43:29,120
DEFINING THE CRITICAL QUALITY

2442
01:43:29,120 --> 01:43:32,880
ATTRIBUTES DEPENDS ON THE CELL

2443
01:43:32,880 --> 01:43:35,120
SOURCE. DIFFERENT CELL SOURCES

2444
01:43:35,120 --> 01:43:37,360
MAY HAVE VERY DIFFERENT AFFECTS.

2445
01:43:37,360 --> 01:43:39,800
SO IF WE WANT TO TRY TO COMPARE

2446
01:43:39,800 --> 01:43:42,680
ONE STUDY TO ANOTHER, WE NEED TO

2447
01:43:42,680 --> 01:43:44,560
KNOW MORE ABOUT THE TISSUE

2448
01:43:44,560 --> 01:43:47,000
SOURCE AND WHAT THE CRITICAL

2449
01:43:47,000 --> 01:43:48,520
QUALITY CHARACTERISTICS ARE, OF

2450
01:43:48,520 --> 01:43:54,560
THAT POPULATION.  WANT YOUR

2451
01:43:54,560 --> 01:43:56,400
THOUGHTS ON THAT SUBJECT AND

2452
01:43:56,400 --> 01:43:57,800
SURE GEORGE PROBABLY HAS

2453
01:43:57,800 --> 01:43:58,160
THOUGHTS TO.

2454
01:43:58,160 --> 01:44:02,320
>>MY RESPONSE IS AMEN.
YOU SAY

2455
01:44:02,320 --> 01:44:03,880
THE PROBLEM WELL AND EXPERTS IN

2456
01:44:03,880 --> 01:44:05,240
THE FIELD HELP US, COULDN'T

2457
01:44:05,240 --> 01:44:07,000
AGREE MORE.  GOES WITHOUT

2458
01:44:07,000 --> 01:44:08,760
SAYING, YOU STATED THAT WELL. WE

2459
01:44:08,760 --> 01:44:11,080
NEED TO DO THAT. CLEARLY WE NEED

2460
01:44:11,080 --> 01:44:12,720
TO CHARACTERIZE WHAT WE ARE

2461
01:44:12,720 --> 01:44:13,720
PUTTING IN THE PATIENT.

2462
01:44:13,720 --> 01:44:18,320
>>THANK YOU, CHRISTIAN

2463
01:44:18,320 --> 01:44:18,600
LATTERMANN.

2464
01:44:18,600 --> 01:44:19,920
>>SCOTT, THANK YOU VERY
MUCH

2465
01:44:19,920 --> 01:44:25,400
FOR THAT OVERVIEW. THAT WAS

2466
01:44:25,400 --> 01:44:26,720
BEAUTIFUL. ONE OF THE QUESTIONS

2467
01:44:26,720 --> 01:44:28,200
THAT I WRESTLE WITH LOOKING AT

2468
01:44:28,200 --> 01:44:30,360
CHRONIC INFLAMMATION IN THE

2469
01:44:30,360 --> 01:44:33,600
CONTEXT OF PTOA AND TRY TO

2470
01:44:33,600 --> 01:44:38,200
COMPARE TO CHRONIC INFLAMMATORY

2471
01:44:38,200 --> 01:44:40,000
CONDITIONS, WE COME BACK TO THIS

2472
01:44:40,000 --> 01:44:40,920
CONCEPT OF RESOLUTION OF

2473
01:44:40,920 --> 01:44:44,080
INFLAMMATION. YOU HAVE MENTIONED

2474
01:44:44,080 --> 01:44:45,840
THAT ALSO YOU TOLD US VERY MUCH

2475
01:44:45,840 --> 01:44:49,160
ABOUT THE M 1 M 2 MACROPHAGE

2476
01:44:49,160 --> 01:44:51,080
SWITCH THAT STILL CELLS ARE

2477
01:44:51,080 --> 01:44:54,800
ACTING ON. ONE OF THE CLINICAL

2478
01:44:54,800 --> 01:44:56,840
QUESTIONS I ASK MYSELF AND I

2479
01:44:56,840 --> 01:44:58,760
WANT YOUR OPINION, DO WE DEAL

2480
01:44:58,760 --> 01:45:02,000
WITH THE SITUATION WHERE WE HAVE

2481
01:45:02,000 --> 01:45:02,880
TOO LITTLE INTRAVESICULAR

2482
01:45:02,880 --> 01:45:04,880
RESPONSE TO THE INJURY OR DO WE

2483
01:45:04,880 --> 01:45:07,200
DEAL WITH SITUATION WHERE WE

2484
01:45:07,200 --> 01:45:10,160
HAVE TOO MANY FACTORS THAT ARE

2485
01:45:10,160 --> 01:45:12,480
PREVENTING AN APPROPRIATE

2486
01:45:12,480 --> 01:45:14,240
RESPONSE? BECAUSE WE DO HAVE AN

2487
01:45:14,240 --> 01:45:15,520
INTRINSIC HEALING RESPONSE THAT

2488
01:45:15,520 --> 01:45:18,240
STARTS BUT SOMEHOW IT FAILS. I'M

2489
01:45:18,240 --> 01:45:20,800
TRYING TO FIGURE OUT BASICALLY

2490
01:45:20,800 --> 01:45:21,840
WHAT DO YOU THINK IS HAPPENING

2491
01:45:21,840 --> 01:45:23,320
HERE?

2492
01:45:23,320 --> 01:45:26,120
>>MY SIMPLE ANSWER OR
CONCEPT

2493
01:45:26,120 --> 01:45:29,080
IS THAT CLEARLY RIGHT. THERE IS

2494
01:45:29,080 --> 01:45:30,640
INJURY INDUCE TRAUMA INDUCES

2495
01:45:30,640 --> 01:45:32,520
INFLAMMATION. INFLAMMATION TURNS

2496
01:45:32,520 --> 01:45:33,760
ON INTRINSIC HEALING RESPONSE,

2497
01:45:33,760 --> 01:45:35,160
GOOD THING. PROBLEM IS IT IS

2498
01:45:35,160 --> 01:45:37,440
CHRONIC UNRESOLVED INFLAMMATION

2499
01:45:37,440 --> 01:45:39,240
THAT YOU TAKE A LEFT TURN GO

2500
01:45:39,240 --> 01:45:41,120
DOWN THE WRONG PATHWAY SO MAYBE

2501
01:45:41,120 --> 01:45:44,240
WITH INJURY YOU -- THE INTRINSIC

2502
01:45:44,240 --> 01:45:46,560
INNATE SYSTEMS ARE FOR TISSUE

2503
01:45:46,560 --> 01:45:48,240
GENERATION ARE HEALING ARE

2504
01:45:48,240 --> 01:45:50,200
STIMULATED BUT CHRONIC

2505
01:45:50,200 --> 01:45:51,440
INFLAMMATION THEY LEAD YOU THE

2506
01:45:51,440 --> 01:45:53,200
WRONG PATHWAY IF YOU WILL, THAT

2507
01:45:53,200 --> 01:45:54,560
IS INSTEAD OF REGENERATIVE

2508
01:45:54,560 --> 01:45:57,360
TISSUE YOU GO TO FIBROSIS

2509
01:45:57,360 --> 01:45:59,520
PATHWAY. INFLAMMATION IS HIGHLY

2510
01:45:59,520 --> 01:46:02,240
COMPLEX BUT IN MY MIND CHRONIC

2511
01:46:02,240 --> 01:46:06,160
UNRESOLVED INFLAMMATION IS

2512
01:46:06,160 --> 01:46:10,360
PRIMARY FACTOR. AS PROBLEM WITH

2513
01:46:10,360 --> 01:46:10,800
ANY DISEASE STATES.

2514
01:46:10,800 --> 01:46:12,720
>>SO THE QUESTION THAT
I'M

2515
01:46:12,720 --> 01:46:18,320
TRYING TO GET AT IS WE CAN SHUT

2516
01:46:18,320 --> 01:46:20,960
DOWN INFLAMMATION RELATIVELY

2517
01:46:20,960 --> 01:46:22,520
QUICKLY EVEN IN A KNEE JOINT. WE

2518
01:46:22,520 --> 01:46:25,920
HAVE DONE THAT IN CLINICAL

2519
01:46:25,920 --> 01:46:27,880
TRIALS WE HAVE DONE WITH

2520
01:46:27,880 --> 01:46:29,760
CORTISOL FOR EXAMPLE BUT

2521
01:46:29,760 --> 01:46:31,120
QUESTION, IS THAT A GOOD THING,

2522
01:46:31,120 --> 01:46:35,000
JUST TIMING ISSUE? OR IS IT JUST

2523
01:46:35,000 --> 01:46:37,520
SOMETHING THAT IS TOO TEMPORARY

2524
01:46:37,520 --> 01:46:39,960
AND BASICALLY WILL GO DOWN THE

2525
01:46:39,960 --> 01:46:43,840
WRONG PATH BECAUSE SYSTEM IS

2526
01:46:43,840 --> 01:46:49,280
OVERCOME BY FACTORS THAT WILL

2527
01:46:49,280 --> 01:46:51,080
OVERWHELM ANY RESTORATION OF

2528
01:46:51,080 --> 01:46:51,840
HOMEOSTASIS SO TO SPEAK NO

2529
01:46:51,840 --> 01:46:54,720
MATTER WHAT.

2530
01:46:54,720 --> 01:46:55,320
SPEAKER5: COMPLEX BECAUSE I

2531
01:46:55,320 --> 01:46:58,400
THINK WE NEED A MORE NUANCED

2532
01:46:58,400 --> 01:47:01,600
APPROACH, IF YOU HIT WITH

2533
01:47:01,600 --> 01:47:02,600
CORTICOSTEROID, NICE WORK BUT

2534
01:47:02,600 --> 01:47:07,120
MAYBE INFLAMMATION IS VERY

2535
01:47:07,120 --> 01:47:08,480
COMPLEX, THERE ARE MEDIATORS,

2536
01:47:08,480 --> 01:47:09,840
CYTOKINES MAYBE BLOCK OTHERS WE

2537
01:47:09,840 --> 01:47:11,120
DON'T AND THEN YOU HAVE TIMING

2538
01:47:11,120 --> 01:47:14,680
ISSUES. SO WE ARE TIP OF THE

2539
01:47:14,680 --> 01:47:15,840
ICEBERG AS FAR AS UNDERSTANDING

2540
01:47:15,840 --> 01:47:18,240
HOW WE AS CLINICIANS MODULATE

2541
01:47:18,240 --> 01:47:19,360
INFLAMMATION. THAT IS OUR

2542
01:47:19,360 --> 01:47:21,040
CHALLENGE. YOU HAVE PATIENTS IN

2543
01:47:21,040 --> 01:47:23,280
THE OFFICE IN CLINIC, SWOLLEN

2544
01:47:23,280 --> 01:47:25,480
KNEE, I CAN PUT A STEROID IN BUT

2545
01:47:25,480 --> 01:47:27,440
SO VARIABLE, TIMING OF INJURY,

2546
01:47:27,440 --> 01:47:29,440
OTHER FACTORS IN THAT PATIENT'S

2547
01:47:29,440 --> 01:47:31,120
KNEE. DO I NEED TO REPEAT THIS

2548
01:47:31,120 --> 01:47:33,120
THERAPY. I THINK WE NEED A MUCH

2549
01:47:33,120 --> 01:47:35,120
MORE REFINED APPROACH TO

2550
01:47:35,120 --> 01:47:39,960
MANAGING INFLAMMATION.

2551
01:47:39,960 --> 01:47:41,760
>>DANIEL WHITE. 

2552
01:47:41,760 --> 01:47:43,440
>>THANK YOU FOR THE
WONDERFUL

2553
01:47:43,440 --> 01:47:44,840
PRESENTATION, DR. RODEO.

2554
01:47:44,840 --> 01:47:47,480
WONDERING IF YOU CAN COMMENT ON

2555
01:47:47,480 --> 01:47:48,840
THE QUALITY OF THE CLINICAL

2556
01:47:48,840 --> 01:47:52,240
TRIALS THAT HAD CLINICAL

2557
01:47:52,240 --> 01:47:53,960
OUTCOMES IN PARTICULARLY

2558
01:47:53,960 --> 01:47:56,480
INTERESTED IN WHETHER BLINDING

2559
01:47:56,480 --> 01:48:00,800
WAS DONE, WAS THERE A PLACEBO IN

2560
01:48:00,800 --> 01:48:07,120
ADDITION TO STEM CELL? WHAT

2561
01:48:07,120 --> 01:48:08,680
PEAKS MY QUESTION ABOUT THIS IN

2562
01:48:08,680 --> 01:48:11,560
OTHER PRP STUDIES THERE'S

2563
01:48:11,560 --> 01:48:14,360
VARIABLE AND QUALITY AND WE MOW

2564
01:48:14,360 --> 01:48:16,120
PLACEBO MAKES A DIFFERENCE WITH

2565
01:48:16,120 --> 01:48:18,200
CLINICAL OUTCOMES AND GIVEN NO

2566
01:48:18,200 --> 01:48:19,560
BENEFICIAL EFFECTS STRUCTURAL SO

2567
01:48:19,560 --> 01:48:21,000
FAR, I UNDERSTAND PRELIMINARY

2568
01:48:21,000 --> 01:48:22,320
STUDIES BASIC QUESTION HOW MUCH

2569
01:48:22,320 --> 01:48:23,880
IS THIS PLACEBO EFFECT?

2570
01:48:23,880 --> 01:48:26,880
>>GREAT QUESTION. OVERALL
STUDY

2571
01:48:26,880 --> 01:48:28,120
METHODOLOGY,S MODERATE TO POOR

2572
01:48:28,120 --> 01:48:30,280
IN A LOT OF STUDIES WHAT YOU CAN

2573
01:48:30,280 --> 01:48:32,200
SAY ABOUT A LOT OF LITERATURE,

2574
01:48:32,200 --> 01:48:35,000
THE ISSUE TO CHARACTERIZE TWO

2575
01:48:35,000 --> 01:48:36,320
THINGS, DR. ROBEY BROUGHT ONE,

2576
01:48:36,320 --> 01:48:37,320
CHARACTERIZE WHAT WE ARE PUTTING

2577
01:48:37,320 --> 01:48:44,240
IN PATIENT, SO CALLED ME MEBO

2578
01:48:44,240 --> 01:48:47,120
INFORMATION. MINIMAL, BIOLOG 

2579
01:48:47,120 --> 01:48:49,640
BIOLOGICAL, WHAT CELLS ARE USING

2580
01:48:49,640 --> 01:48:51,920
PRP HOW WOULD -- IT WAS OBTAINED

2581
01:48:51,920 --> 01:48:53,360
PREPARED ET CETERA, WE NEED TO

2582
01:48:53,360 --> 01:48:54,440
CHARACTERIZE WHAT IS PUT IN THE

2583
01:48:54,440 --> 01:48:56,000
PATIENT AND OTHER SIDE THE

2584
01:48:56,000 --> 01:48:57,640
PATIENT PHENOTYPE BACK TO

2585
01:48:57,640 --> 01:48:59,280
CONNIE'S EARLIER QUESTION.

2586
01:48:59,280 --> 01:49:01,720
PATIENT AGE GENDER MEDICAL

2587
01:49:01,720 --> 01:49:03,480
CO-MORBIDITIES.  ALL THESE

2588
01:49:03,480 --> 01:49:07,560
ISSUES. STUDIES OFTEN DON'T HAVE

2589
01:49:07,560 --> 01:49:09,720
ALL THAT INFORMAT INFORMATION. S

2590
01:49:09,720 --> 01:49:10,640
COMMENT, WE FOOD THAT DATA IN

2591
01:49:10,640 --> 01:49:13,160
OUR CLINICAL STUDIES. BE

2592
01:49:13,160 --> 01:49:14,960
IMPORTANCE OF NIGH FOR WELL

2593
01:49:14,960 --> 01:49:17,360
DESIGNED CLINICAL TRIALS WHICH

2594
01:49:17,360 --> 01:49:22,160
ARE CHALLENGING. THAT IS IS WHAE

2595
01:49:22,160 --> 01:49:22,640
NEED IN THIS FIELD.

2596
01:49:22,640 --> 01:49:25,400
>>REALLY GREAT TALK.
ENJOYED

2597
01:49:25,400 --> 01:49:27,840
THAT. I WAS PART OF THE ACADEMY

2598
01:49:27,840 --> 01:49:30,200
PANEL, ABOUT TEN PEOPLE, WE HAD

2599
01:49:30,200 --> 01:49:33,400
TO PUT SOME TREATIES TOGETHER ON

2600
01:49:33,400 --> 01:49:37,960
ALL THE HIGH LEVEL STUDIES FOR

2601
01:49:37,960 --> 01:49:42,280
TREATING THE OA MESENCHYMAL

2602
01:49:42,280 --> 01:49:43,840
CELLS, IT ENDED UP BEING EXACTLY

2603
01:49:43,840 --> 01:49:45,600
WHAT YOU SAID, VERY INCLUSIVE

2604
01:49:45,600 --> 01:49:47,280
AND EVERYBODY USING DIFFERENT

2605
01:49:47,280 --> 01:49:48,240
CONCENTRATIONS OF CELLS WITH

2606
01:49:48,240 --> 01:49:51,120
DIFFERENT PROCUREMENT TECHNI

2607
01:49:51,120 --> 01:49:52,680
TECHNIQUES. DO YOU THINK IT IS

2608
01:49:52,680 --> 01:49:58,040
POSSIBLE THIS GROUP COULD PUT

2609
01:49:58,040 --> 01:49:59,840
TOGETHER A TREATISE FOR GOING

2610
01:49:59,840 --> 01:50:03,800
FORWARD ON THIS IS THE MINIMAL

2611
01:50:03,800 --> 01:50:05,360
-- MAYBE THIS IS MINIMAL

2612
01:50:05,360 --> 01:50:09,080
INFORMATION YOU SHOULD TRY TO

2613
01:50:09,080 --> 01:50:11,200
COLLECT ON YOUR TAKING -- THIS

2614
01:50:11,200 --> 01:50:13,080
IS THE WAY TO CONDUCT SOME OF

2615
01:50:13,080 --> 01:50:14,520
THE STUDIES SO WE HAVE A LITTLE

2616
01:50:14,520 --> 01:50:18,440
MORE STAND STANDARDIZATION SO WE

2617
01:50:18,440 --> 01:50:19,760
DO IT AGAIN MANY FIVE YEARS WE

2618
01:50:19,760 --> 01:50:21,560
HAVE A BETTER HANDLE ON THIS

2619
01:50:21,560 --> 01:50:23,680
FIELD? COULD THAT BE A RESULT OF

2620
01:50:23,680 --> 01:50:25,000
THIS MEETING?

2621
01:50:25,000 --> 01:50:30,000
>>LOOK AT PAPER FROM BOB
LAPROD

2622
01:50:30,000 --> 01:50:32,720
2017 IAN MURRAY, TOOK US DOWN

2623
01:50:32,720 --> 01:50:34,040
DOING THIS, SUGGESTING THE FACT

2624
01:50:34,040 --> 01:50:35,080
THAT WE SHOULD CHARACTERIZE,

2625
01:50:35,080 --> 01:50:36,200
MAYBE WE NEED TO REVISIT THAT

2626
01:50:36,200 --> 01:50:39,960
AND WE HAVE A MORE REFINED

2627
01:50:39,960 --> 01:50:41,040
ABILITY OR ABILITY TO HAVE A

2628
01:50:41,040 --> 01:50:45,200
MORE REFINED ANALYSIS BUT

2629
01:50:45,200 --> 01:50:47,440
CLEARLY POINTS OUT IMPORTANCE OF

2630
01:50:47,440 --> 01:50:49,440
CHARACTERIZING FORMULATION OF

2631
01:50:49,440 --> 01:50:50,560
PATIENTS IN ADDITION TO

2632
01:50:50,560 --> 01:50:51,360
CHARACTERIZING THE PATIENT,

2633
01:50:51,360 --> 01:50:54,920
RECIPIENT.

2634
01:50:54,920 --> 01:50:57,240
>>DAN YOU HAD YOUR HAND
UP A

2635
01:50:57,240 --> 01:51:00,000
WHILE, DID YOU STILL HAVE A

2636
01:51:00,000 --> 01:51:00,280
QUESTION?

2637
01:51:00,280 --> 01:51:03,000
>>THANKS CONNIE. THANK
YOU VERY

2638
01:51:03,000 --> 01:51:04,560
MUCH, SCOTT.  IT WAS MORE

2639
01:51:04,560 --> 01:51:05,600
REFLECTION, QUESTION TO SCOTT

2640
01:51:05,600 --> 01:51:08,120
AND MAYBE INFO FOR THE GROUP.

2641
01:51:08,120 --> 01:51:11,240
SCOTT WHERE DO YOU SEE ROOM FOR

2642
01:51:11,240 --> 01:51:13,040
MAKING BETTER STEPS IN USING

2643
01:51:13,040 --> 01:51:15,000
STEM CELL BASED THERAPIES AND I

2644
01:51:15,000 --> 01:51:18,640
WILL OPEN TO CARTILAGE REPAIR

2645
01:51:18,640 --> 01:51:19,880
AND OSTEOARTHRITIS. I LIKE

2646
01:51:19,880 --> 01:51:21,440
TREATING SOONER RATHER THAN

2647
01:51:21,440 --> 01:51:23,120
LATER SO AFTER REVIEWING THIS

2648
01:51:23,120 --> 01:51:26,200
AND SHARING THAT BE US WHERE YOU

2649
01:51:26,200 --> 01:51:29,520
TAKE IT WHETHER YOU SEE RESEARCH

2650
01:51:29,520 --> 01:51:33,240
HAS BEEN ALREADY. FOR GROUP

2651
01:51:33,240 --> 01:51:34,440
LARGER INFORMATION, IMPORTANT TO

2652
01:51:34,440 --> 01:51:37,000
KNOW WE HAVE BEEN DOING THESE

2653
01:51:37,000 --> 01:51:39,600
ALLOGENEIC MSC WORK, TREATING

2654
01:51:39,600 --> 01:51:41,840
PATIENTS WITH ALLOGENEIC MSC,

2655
01:51:41,840 --> 01:51:44,440
FOR THE REASON DR. ELISSEEFF

2656
01:51:44,440 --> 01:51:46,240
SAID AND DR. LATTERMANN REFERRED

2657
01:51:46,240 --> 01:51:48,120
TO, MSCs ARE BETTER GAUGING

2658
01:51:48,120 --> 01:51:49,880
THE JOINT AND PROVIDING

2659
01:51:49,880 --> 01:51:51,440
APPROPRIATE IMMUNE MODULATION

2660
01:51:51,440 --> 01:51:52,880
THAT ARE INJECTION OF

2661
01:51:52,880 --> 01:51:54,120
CORTICOSTEROIDS ARE. SO MY

2662
01:51:54,120 --> 01:51:55,760
FEELING IS THAT WE SHOULD TREAT

2663
01:51:55,760 --> 01:51:58,080
BLACK BOX OF MSCs BECAUSE WE

2664
01:51:58,080 --> 01:51:59,840
DON'T UNDERSTAND THEM FULLY AS A

2665
01:51:59,840 --> 01:52:02,520
BENEFICIAL ASPECT AS PART OF OUR

2666
01:52:02,520 --> 01:52:03,760
THERAPY BEING SMARTER THAN WHEN

2667
01:52:03,760 --> 01:52:06,040
WE USE AUTOLOGOUS OR WHEN WE USE

2668
01:52:06,040 --> 01:52:07,760
EXTERNALLY APPLIED CHEMICALS BUT

2669
01:52:07,760 --> 01:52:09,560
MY QUESTION IS, WHERE DO YOU

2670
01:52:09,560 --> 01:52:11,600
THINK US TAKING MSCs AS PART

2671
01:52:11,600 --> 01:52:13,720
OF THERAPEUTICS SHOULD GO FROM

2672
01:52:13,720 --> 01:52:15,000
RESEARCH PERSPECTIVE?

2673
01:52:15,000 --> 01:52:16,440
>>CHARACTERIZING THE CELL

2674
01:52:16,440 --> 01:52:19,640
FORMULATION, I THINK IDENTIFYING

2675
01:52:19,640 --> 01:52:22,640
THE OPTIMAL CELL FORMULATION FOR

2676
01:52:22,640 --> 01:52:24,080
DIFFERENT TISSUE, ONE SIZE

2677
01:52:24,080 --> 01:52:27,080
DOESN'T FIT ALL, ONE FOR TENDON

2678
01:52:27,080 --> 01:52:28,600
DIFFERENT THAN CARTILAGE

2679
01:52:28,600 --> 01:52:29,880
DIFFERENT FOR MUSCLE AND BONE.

2680
01:52:29,880 --> 01:52:32,920
CHARACTERIZE WHAT WE NEED TO

2681
01:52:32,920 --> 01:52:35,080
TREAT SPECIFIC TISSUE PATHOLOGY

2682
01:52:35,080 --> 01:52:38,080
AND CHARACTERIZE CELL POPULATION

2683
01:52:38,080 --> 01:52:39,440
AS PAM ROBEY ARTICULATED. 

2684
01:52:39,440 --> 01:52:41,400
ANOTHER AREA IS INTERACTION WITH

2685
01:52:41,400 --> 01:52:42,960
INTRINSIC STEM CELL, PROGENITOR

2686
01:52:42,960 --> 01:52:44,600
CELL POPULATION IN TISSUES AND

2687
01:52:44,600 --> 01:52:46,680
IMPORTANT ROLE OF IMMUNE CELLS

2688
01:52:46,680 --> 01:52:49,200
IN THAT PROCESS. THE PARACRINE

2689
01:52:49,200 --> 01:52:51,960
EFFECT OF THESE MATERIAL YOUR

2690
01:52:51,960 --> 01:52:56,480
EXOSOME WORK WILL GET TO THAT.

2691
01:52:56,480 --> 01:52:58,480
THESE MOLECULES FROM CELLS, HOW

2692
01:52:58,480 --> 01:52:59,960
DOES THAT AFFECT INTRINSIC

2693
01:52:59,960 --> 01:53:03,920
PROGENITOR CELLS IN TISSUES?

2694
01:53:03,920 --> 01:53:05,960
>>FULLY AGREE BUT ALSO
WHAT

2695
01:53:05,960 --> 01:53:07,520
THAT MEANS IS INTERESTING FOR

2696
01:53:07,520 --> 01:53:09,040
OUR FIELD TO RESPONDS TO THAT

2697
01:53:09,040 --> 01:53:13,880
YOU HAVE TO GO ALLOGENEIC IF

2698
01:53:13,880 --> 01:53:14,480
CHARACTERIZIZATION AND

2699
01:53:14,480 --> 01:53:15,600
RELIABILITY EVAPORABILITY IS A

2700
01:53:15,600 --> 01:53:18,000
BIG THING AND COLLEAGUES FIND IT

2701
01:53:18,000 --> 01:53:19,120
CONSIDERABLE CHALLENGE BECAUSE

2702
01:53:19,120 --> 01:53:20,800
REGULATORY BURDEN ON ALLOGENEIC

2703
01:53:20,800 --> 01:53:21,560
WORK. HOW DO YOU SEE THAT

2704
01:53:21,560 --> 01:53:23,720
HAPPEN?

2705
01:53:23,720 --> 01:53:25,640
>>THOSE ARE CHALLENGES
FOR US,

2706
01:53:25,640 --> 01:53:27,040
THAT'S THE REGULATORY SIDE OF

2707
01:53:27,040 --> 01:53:32,080
THINGS AND THE NEED TO CONTINUE

2708
01:53:32,080 --> 01:53:34,280
TO RELATIONLATORY ENVIRONMENT

2709
01:53:34,280 --> 01:53:36,480
LANDSCAPE INVOLVES.

2710
01:53:36,480 --> 01:53:40,480
>>MOVING ON, THEY ASKED
US TO

2711
01:53:40,480 --> 01:53:43,880
DO SO. WITH THAT I WILL -- WE

2712
01:53:43,880 --> 01:53:50,160
WILL MOVE TO DR. MARK HOCHBERG,

2713
01:53:50,160 --> 01:53:52,000
PLEASURE, PROFESSOR MEDICINE

2714
01:53:52,000 --> 01:53:53,240
EPIDEMIOLOGY AND PUBLIC HEALTH

2715
01:53:53,240 --> 01:53:55,040
UNIVERSITY OF MARYLAND. HE IS

2716
01:53:55,040 --> 01:53:56,920
HEAD OF DIVISION OF RHEUMATOLOGY

2717
01:53:56,920 --> 01:53:58,240
AND CLINICAL IMMUNOLOGY AS WELL

2718
01:53:58,240 --> 01:53:59,480
AS VICE CHAIR IN THE DEPARTMENT

2719
01:53:59,480 --> 01:54:00,640
OF MEDICINE, AT UNIVERSITY OF

2720
01:54:00,640 --> 01:54:04,320
MARYLAND. BRIEFLY MENTION VERY

2721
01:54:04,320 --> 01:54:08,200
DISTINGUISHED AWARDS FROM DR.

2722
01:54:08,200 --> 01:54:10,000
HOCHBERG OVER THE YEARS FROM THE

2723
01:54:10,000 --> 01:54:10,720
DISTINGUISHED CLINICAL

2724
01:54:10,720 --> 01:54:11,800
INVESTIGATOR WORK, AMERICAN

2725
01:54:11,800 --> 01:54:13,040
COLLEGE OF RHEUMATOLOGY,

2726
01:54:13,040 --> 01:54:15,480
LIFETIME ACHIEVEMENT AWARD FROM

2727
01:54:15,480 --> 01:54:17,280
ORSE, PAST PRESIDENT OF THE U.S.

2728
01:54:17,280 --> 01:54:19,320
BONE AND JOINT INITIATIVE. VERY

2729
01:54:19,320 --> 01:54:22,040
ACCOMPLISHED IN HIS FIELD. HE IS

2730
01:54:22,040 --> 01:54:24,880
CURRENTLY PI BALTIMORE CLINICAL

2731
01:54:24,880 --> 01:54:27,320
SECTOR FOR THE OA INITIATIVE. HE

2732
01:54:27,320 --> 01:54:29,960
WILL TALK TO US ON THE ROLE OF

2733
01:54:29,960 --> 01:54:31,040
CHONDROGENNIC SMALL MOLECULES.

2734
01:54:31,040 --> 01:54:39,240
THANK YOU, DR. HOCKBU HOCK BERG.

2735
01:54:39,240 --> 01:54:42,560
>>THANK YOU DR. RODEO AND
DR.

2736
01:54:42,560 --> 01:54:44,520
CHU. I WAS TASKED TO SPEAK ON

2737
01:54:44,520 --> 01:54:47,600
CARTILAGE REGENERATION BY

2738
01:54:47,600 --> 01:54:48,960
CHONDROGENNIC SMALL MOLECULES. 

2739
01:54:48,960 --> 01:54:53,560
AS I MENTIONED DURING THE

2740
01:54:53,560 --> 01:54:55,440
INITIAL PART OF THIS MEETING I

2741
01:54:55,440 --> 01:54:56,480
HAVE NO PERSONAL EXPERIENCE IN

2742
01:54:56,480 --> 01:55:00,000
THIS. LET ME MOVE FORWARD I

2743
01:55:00,000 --> 01:55:10,560
GUESS.  I'M SHOWING DISCLOSURES 

2744
01:55:19,160 --> 01:55:21,120
FOR THE REASON THERE'S TWO

2745
01:55:21,120 --> 01:55:25,920
COMPANIES WHICH ARE IN IN BOLD

2746
01:55:25,920 --> 01:55:33,120
PRESENTING TATTED FROM BOTH

2747
01:55:33,120 --> 01:55:33,880
COMPANIES IN TERMS OF SMALL

2748
01:55:33,880 --> 01:55:44,320
MOLECULES.  WE ARE TALKING

2749
01:55:49,600 --> 01:55:50,720
OSTEOARTHRITIS THERE IS ONE USE

2750
01:55:50,720 --> 01:55:52,800
OF THE TERM DEGENERATIVE DURING

2751
01:55:52,800 --> 01:55:53,920
THE FIRST TWO HOURS OF THIS

2752
01:55:53,920 --> 01:55:58,160
MEETING. AND BUT MAJORITY OF

2753
01:55:58,160 --> 01:56:01,960
PEOPLE HAVE USED DEGRADATION. .

2754
01:56:01,960 --> 01:56:04,280
SO AS DR. RODEO JUST POINTED

2755
01:56:04,280 --> 01:56:09,840
OUT, THIS IS AN IMMUNE MEDIATED

2756
01:56:09,840 --> 01:56:11,080
INFLAMMATORY CONDITION. WE HAVE

2757
01:56:11,080 --> 01:56:15,040
ACTIVATION OF THE CHONDROCYTE,

2758
01:56:15,040 --> 01:56:18,160
INITIALLY IN SO CALLED

2759
01:56:18,160 --> 01:56:19,080
IDIOPATHIC OSTEOARTHRITIS,

2760
01:56:19,080 --> 01:56:22,160
PRESUMABLY STIMULATED BY

2761
01:56:22,160 --> 01:56:26,640
ABNORMAL BIOMECHANICAL LOAD

2762
01:56:26,640 --> 01:56:28,200
WHICH LEADS CHONDROCYTE TO

2763
01:56:28,200 --> 01:56:34,080
GENERATE INFLAMMATORY CYTOKINES 

2764
01:56:34,080 --> 01:56:35,520
INFLAMMATORY CYTOKINES

2765
01:56:35,520 --> 01:56:36,720
SIMPLISTICALLY WILL LEAD TO

2766
01:56:36,720 --> 01:56:37,720
DEGRADATION OF THE CARTILAGE

2767
01:56:37,720 --> 01:56:41,400
MATRIX MEDIATED BY ENZYMES

2768
01:56:41,400 --> 01:56:44,920
PRODUCED BY THE CHONDROCYTE WITH

2769
01:56:44,920 --> 01:56:46,760
THE ASSOCIATED SUBCHONDRAL BONE

2770
01:56:46,760 --> 01:56:52,640
CHANGES. PEOPLE IDENTIFIED ROLES

2771
01:56:52,640 --> 01:56:55,800
FOR BONEMORPHO GENIC PROTEIN,

2772
01:56:55,800 --> 01:56:57,600
TGF BETA AND WINT PATHWAY

2773
01:56:57,600 --> 01:56:59,480
LIGANDS WITH REGARD TO

2774
01:56:59,480 --> 01:57:00,560
SUBCHONDRAL BONE CHANGES. I

2775
01:57:00,560 --> 01:57:04,800
WON'T TALK ABOUT THAT VASCULAR

2776
01:57:04,800 --> 01:57:09,200
ENVATION OF THE ARTICULAR

2777
01:57:09,200 --> 01:57:11,440
CARTILAGE, ET CETERA.  I WILL

2778
01:57:11,440 --> 01:57:14,000
FOCUS ON CHONDROCYTE CHANGES

2779
01:57:14,000 --> 01:57:15,240
THAT ARE CURRENTLY

2780
01:57:15,240 --> 01:57:17,640
OSTEOARTHRITIS AND THESE

2781
01:57:17,640 --> 01:57:20,760
SUMMARIZE IN THE UPPER RIGHT

2782
01:57:20,760 --> 01:57:22,200
HAND BOX IN THIS SLIDE WHICH

2783
01:57:22,200 --> 01:57:25,200
COMES FROM PAPER PUBLISHED TEN

2784
01:57:25,200 --> 01:57:28,680
YEARS AGO.  SO THERE IS

2785
01:57:28,680 --> 01:57:31,680
CHONDROCYTE PROLIFERATION.

2786
01:57:31,680 --> 01:57:34,400
INITIALLY INCREASE IN MATRIX

2787
01:57:34,400 --> 01:57:35,760
SYNTHESIS.  SO WE WANT TO

2788
01:57:35,760 --> 01:57:39,400
HARNESS THIS REGENERATIVE

2789
01:57:39,400 --> 01:57:41,200
CAPACITY OF THE CHONDROCYTE AS

2790
01:57:41,200 --> 01:57:48,680
IT PROLIVE RATES IN CURTILAGE.  

2791
01:57:48,680 --> 01:57:49,480
WITHOUT PRODUCTION OF

2792
01:57:49,480 --> 01:57:51,040
INFLAMMATORY CYTOKINES, WITHOUT

2793
01:57:51,040 --> 01:57:53,040
PRODUCTION OF TISSUE DESTRUCTIVE

2794
01:57:53,040 --> 01:57:55,800
ENZYMES AND TRYING TO RESTORE

2795
01:57:55,800 --> 01:57:59,280
NORMAL PHENOTYPE TO THE CONT

2796
01:57:59,280 --> 01:58:05,920
CONTRACYTE. -- CHONDROCYTE. IT'S

2797
01:58:05,920 --> 01:58:08,320
BEEN DISCUSSED ABOUT THE ROLE OF

2798
01:58:08,320 --> 01:58:11,920
INFLAMMATORY CYTOKINES, AND

2799
01:58:11,920 --> 01:58:15,240
IMMUNE SYSTEM IN PATIENTS WITH

2800
01:58:15,240 --> 01:58:16,160
OSTEOARTHRITIS AND DEVELOPMENT

2801
01:58:16,160 --> 01:58:20,760
OF OSTEOARTHRITIS. I WANT TO

2802
01:58:20,760 --> 01:58:23,640
MENTION THERE'S A ROLE FOR

2803
01:58:23,640 --> 01:58:24,280
ANTI-INFLAMMATORY CYTOKINES

2804
01:58:24,280 --> 01:58:27,160
WHICH ARE PRODUCED BY THE

2805
01:58:27,160 --> 01:58:30,280
CHONDROCYTE INCLUDING IL 4 AND

2806
01:58:30,280 --> 01:58:32,280
IL 10 AND THERE'S SOME WORK NOW

2807
01:58:32,280 --> 01:58:37,680
IN TERMS OF TRYING TO LOOK AT IL

2808
01:58:37,680 --> 01:58:39,800
10, PROTEIN NOT SMALL MOLECULE

2809
01:58:39,800 --> 01:58:44,720
IN TERMS OF ITS EFFICACY FOR

2810
01:58:44,720 --> 01:58:45,760
OSTEOARTHRITIS AND CARTILAGE

2811
01:58:45,760 --> 01:58:53,160
REGENERATION. SO THE STRATEGIES

2812
01:58:53,160 --> 01:58:58,000
DISCUSSED INCLUDE REPAIR

2813
01:58:58,000 --> 01:59:00,720
STRATEGIES, WE HAVEN'T TALKED

2814
01:59:00,720 --> 01:59:02,440
MICROFRACTURE OF THE SUBCHONDRAL

2815
01:59:02,440 --> 01:59:05,080
BONE, AUTOLOGOUS CHONDROCYTE

2816
01:59:05,080 --> 01:59:08,760
TRANSPLANTATION. THE USE OF

2817
01:59:08,760 --> 01:59:09,920
MESENCHYMAL STEM CELLS OR

2818
01:59:09,920 --> 01:59:11,920
STROMAL CELLS AS WELL AS TISSUE

2819
01:59:11,920 --> 01:59:14,280
ENGINEERED CARTILAGE. ALL THESE

2820
01:59:14,280 --> 01:59:16,200
HAVE BEEN OR WILL BE DISCUSSED

2821
01:59:16,200 --> 01:59:20,480
DURING THE WORKSHOP TODAY.  KEY

2822
01:59:20,480 --> 01:59:22,680
FOR THIS IS CARTILAGE

2823
01:59:22,680 --> 01:59:26,840
REGENERATION. HOW WE STIMULATE

2824
01:59:26,840 --> 01:59:29,240
CARTILAGE PROGENITOR CELLS OR

2825
01:59:29,240 --> 01:59:34,720
RESIDENT CHONDROCYTES.  SO THIS

2826
01:59:34,720 --> 01:59:37,680
WILL LEAD ME TO SMALL MOLECULE

2827
01:59:37,680 --> 01:59:39,800
COMPOUNDS. I WANT TO SITE THIS

2828
01:59:39,800 --> 01:59:40,720
PAPER AND I DON'T KNOW IF YOU

2829
01:59:40,720 --> 01:59:42,920
CAN SEE THE CITATION ON THE

2830
01:59:42,920 --> 01:59:49,320
BOTTOM OF THE SLIDE. WHICH COMES

2831
01:59:49,320 --> 01:59:53,560
FROM -- EXCUSE ME FOR A SECOND. 

2832
01:59:53,560 --> 01:59:56,400
LEE AND COLLEAGUES FROM CHINA

2833
01:59:56,400 --> 01:59:57,840
PUBLISHED IN BIOMEDICINE AND

2834
01:59:57,840 --> 02:00:00,280
PHARMACO THERAPY IN 2020. SO

2835
02:00:00,280 --> 02:00:04,720
THESE AUTHORS THAT SYSTEMATIC

2836
02:00:04,720 --> 02:00:06,560
REVIEW OF BENCH BIOMEDICAL

2837
02:00:06,560 --> 02:00:08,480
PRE-CLINICAL OR ANIMAL STUDIES

2838
02:00:08,480 --> 02:00:10,600
AS WELL AS HUMAN STUDIES OF

2839
02:00:10,600 --> 02:00:14,880
SMALL MOLECULES. WHICH PROMOTE

2840
02:00:14,880 --> 02:00:16,000
CHONDROGENNIC DIFFERENTIATION OF

2841
02:00:16,000 --> 02:00:18,440
STEM CELLS, SO GOING FROM THE

2842
02:00:18,440 --> 02:00:20,520
STEM CELL TO THE CHONDROCYTE,

2843
02:00:20,520 --> 02:00:23,520
NOT TO THE OSTEOCYTE OR

2844
02:00:23,520 --> 02:00:27,120
OSTEOBLAST OR MUSCLE CELL.  OR

2845
02:00:27,120 --> 02:00:33,880
CHONDROCYTE PROLIFERATION OF

2846
02:00:33,880 --> 02:00:35,760
CHONDROCYTE PROGENITORS

2847
02:00:35,760 --> 02:00:36,520
ASSOCIATED WITH MATRIX

2848
02:00:36,520 --> 02:00:41,320
SYNTHESIS.  BEFORE PRESENTING

2849
02:00:41,320 --> 02:00:45,400
THEIR DATA, I WANT TO MENTION A

2850
02:00:45,400 --> 02:00:47,280
PAPER BY LEE AND COLLEAGUES THIS

2851
02:00:47,280 --> 02:00:49,400
IS A DIFFERENT GROUP. THIS WAS

2852
02:00:49,400 --> 02:00:52,320
PUBLISHED IN OPEN LIFE SCIENCES

2853
02:00:52,320 --> 02:00:55,320
THIS YEAR 2022 WHERE THEY

2854
02:00:55,320 --> 02:00:57,800
IDENTIFIED CHONDROCYTE CELL

2855
02:00:57,800 --> 02:01:00,360
RECEPTORS WHICH CAN BE ENGAGED

2856
02:01:00,360 --> 02:01:02,760
BY SMALL MOLECULES.  THESE

2857
02:01:02,760 --> 02:01:04,840
RECEPTORS ALL LEAD TO THE

2858
02:01:04,840 --> 02:01:09,320
CHONDROCYTE INCREASING MATRIX

2859
02:01:09,320 --> 02:01:10,760
SYNTHESIS, SYNTHESIS OF MATRIX

2860
02:01:10,760 --> 02:01:12,080
COMPONENTS.  THESE INCLUDE

2861
02:01:12,080 --> 02:01:14,440
GROWTH FACTOR ASSOCIATED WITH

2862
02:01:14,440 --> 02:01:15,920
RECEPTORS INCLUDING THOSE FROM

2863
02:01:15,920 --> 02:01:21,000
THE TGF BETA BMP SUPERFAMILY,

2864
02:01:21,000 --> 02:01:24,200
IGF 1, FIBROBLAST GROWTH FACTOR,

2865
02:01:24,200 --> 02:01:27,160
AND EPIDERMAL GROWTH FACTORS.

2866
02:01:27,160 --> 02:01:29,120
THEY IDENTIFY HORMONES

2867
02:01:29,120 --> 02:01:31,360
ASSOCIATED RECEPTORS INCLUDING

2868
02:01:31,360 --> 02:01:33,240
ESTROGEN RECEPTOR, PROGESTERONE,

2869
02:01:33,240 --> 02:01:36,400
AND RECEPTORS FOR ACTIVE

2870
02:01:36,400 --> 02:01:40,280
METABOLITES OF VITAMIN D. THE

2871
02:01:40,280 --> 02:01:45,920
PPAR RECEPTORS, ALPHA BETA AND

2872
02:01:45,920 --> 02:01:47,640
GAMMA, INTEGRINS WHICH BINDS TO

2873
02:01:47,640 --> 02:01:49,480
MOLECULE THE EXTRA CELLULAR

2874
02:01:49,480 --> 02:01:54,400
MATRIX. THEN LRP AND FIZZLE

2875
02:01:54,400 --> 02:01:57,720
PROTEIN WHICH ACTIVATE THE WINT

2876
02:01:57,720 --> 02:02:06,120
BETA CATENIN SIGNALING PATHWAY. 

2877
02:02:06,120 --> 02:02:07,440
LET'S LOOK AT THIS FIGURE FROM

2878
02:02:07,440 --> 02:02:09,680
THE PAPER BY LEE ET AL IN TERMS

2879
02:02:09,680 --> 02:02:13,520
OF SMALL MOLECULES PROMOTING

2880
02:02:13,520 --> 02:02:15,960
CHONDROGENESIS. THEY THEN

2881
02:02:15,960 --> 02:02:18,960
IDENTIFY SEVERAL SMALL

2882
02:02:18,960 --> 02:02:23,560
MOLECULES, WHICH CAN BIND CELL

2883
02:02:23,560 --> 02:02:29,520
SURFACE RECEPTORS TO PROMOTE

2884
02:02:29,520 --> 02:02:31,720
CHONDROGENESIS FROM CHONDROCYTE

2885
02:02:31,720 --> 02:02:36,560
PRECURSORS. SO THESE INCLUDE

2886
02:02:36,560 --> 02:02:41,280
PROSTAGLANDINS, RESVERETROL, ONE

2887
02:02:41,280 --> 02:02:47,360
PRESUMED ACTIVE COMPONENTS, FROM

2888
02:02:47,360 --> 02:02:51,040
GRAPES, WHICH CAN ACTIVATE

2889
02:02:51,040 --> 02:02:57,080
CIRCULAR PATHWAYS.  WE WILL SKIP

2890
02:02:57,080 --> 02:03:00,080
AROUND, SYNBA STATIN AND OTHER

2891
02:03:00,080 --> 02:03:04,960
STATINS, MELATONIN.  STATINS

2892
02:03:04,960 --> 02:03:11,040
AGAIN HERE, MELATONIN HERE. 

2893
02:03:11,040 --> 02:03:12,200
GLUCOCORTICOIDS, AND THEN SMALL

2894
02:03:12,200 --> 02:03:14,880
MOLECULES WHICH CAN ACTIVATE

2895
02:03:14,880 --> 02:03:18,800
HEDGEHOG SIGNALING PATHWAYS.  

2896
02:03:18,800 --> 02:03:22,960
AGAIN HERE YOU HAVE STATINS

2897
02:03:22,960 --> 02:03:24,960
ACTIVATING WINT SIGNALING,

2898
02:03:24,960 --> 02:03:29,600
ACTIVATION OF BMP SIGNALING.  

2899
02:03:29,600 --> 02:03:37,800
ACTIVATION OF TGF BETA. AND

2900
02:03:37,800 --> 02:03:39,480
ACTIVATION OF HORMONE RECEPTORS

2901
02:03:39,480 --> 02:03:41,240
SO SMALL MOLECULES WHICH CAN

2902
02:03:41,240 --> 02:03:44,560
ACTIVATE CELL SURFACE RECEPTORS

2903
02:03:44,560 --> 02:03:51,800
AND LEAD TO CHONDROGENESIS FROM

2904
02:03:51,800 --> 02:03:57,680
PRECURSORS.  THESE FIGURE

2905
02:03:57,680 --> 02:04:02,560
IDENTIFIES SMALL MOLECULES,

2906
02:04:02,560 --> 02:04:04,680
WHICH LEAD TO CHONDROCYTE

2907
02:04:04,680 --> 02:04:06,280
PROLIFERATION OF EXISTING

2908
02:04:06,280 --> 02:04:07,680
CHONDROCYTES AND INCREASE MATRIX

2909
02:04:07,680 --> 02:04:12,160
SYNTHESIS.  SO HERE WE HAVE WINT

2910
02:04:12,160 --> 02:04:14,480
SIGNALING PATHWAY, AND THIS

2911
02:04:14,480 --> 02:04:16,400
GROUP IDENTIFIED GLUCOSAMINE FOR

2912
02:04:16,400 --> 02:04:23,400
EXAMPLE. SOMETHING IN LABORATORY

2913
02:04:23,400 --> 02:04:26,560
AND PRE-CLINICAL MODELS

2914
02:04:26,560 --> 02:04:27,360
SUGGESTING IT MAY HAVE STRUCTURE

2915
02:04:27,360 --> 02:04:29,840
OR DISEASE MODIFYING EFFECTS. 

2916
02:04:29,840 --> 02:04:33,880
BUT THERE IS NOT SHOWN TO BE

2917
02:04:33,880 --> 02:04:38,840
EFFICACIOUS IN HUMAN STUDIES.  

2918
02:04:38,840 --> 02:04:44,480
WHEN WELL CONTROLL CONTROLLED. N

2919
02:04:44,480 --> 02:04:47,520
BINDING TO RECEPTOR AS WELL AS

2920
02:04:47,520 --> 02:04:53,720
AKT TUGNALLING PATHWAYS.  

2921
02:04:53,720 --> 02:04:56,160
SOLITRASIDE TO TGF SIGNALING IS

2922
02:04:56,160 --> 02:04:59,680
SMALL MOLECULE, THE ACTIVATED

2923
02:04:59,680 --> 02:05:02,560
FORM OF VITAMIN D 125 HYDROXY

2924
02:05:02,560 --> 02:05:05,000
VITAMIN D, GROWTH HORMONE AND

2925
02:05:05,000 --> 02:05:06,560
VITAMIN D SIGNALING AS WELL AS

2926
02:05:06,560 --> 02:05:09,360
ESTROGEN AND OTHER COMPOUNDS TO

2927
02:05:09,360 --> 02:05:14,280
ERK SIGNALING. ALL WITH DOWN

2928
02:05:14,280 --> 02:05:15,360
TREATMENT EFFECTS LEADING TO

2929
02:05:15,360 --> 02:05:17,040
ANALOG PHENOTYPE OF THE

2930
02:05:17,040 --> 02:05:27,560
CHONDROCYTE. ANOTHER GROUP HAS

2931
02:05:29,240 --> 02:05:32,840
LOOKED AT NARRATIVE REVIEW OF

2932
02:05:32,840 --> 02:05:34,800
SMALL MOLECULES FOR CHONDROCYTE

2933
02:05:34,800 --> 02:05:41,280
REGENERATION. THIS IS CHEN AND

2934
02:05:41,280 --> 02:05:42,960
COLLEAGUES IN CELLULAR AND

2935
02:05:42,960 --> 02:05:44,720
MOLECULAR LIFE SCIENCES IN 2021.

2936
02:05:44,720 --> 02:05:46,840
THEY PUBLISHED A NARRATIVE

2937
02:05:46,840 --> 02:05:48,680
REVIEW ON DEVELOPMENT OF

2938
02:05:48,680 --> 02:05:50,640
FUNCTIONAL ARTICULAR

2939
02:05:50,640 --> 02:05:53,280
CHONDROCYTES FROM CELLS OR

2940
02:05:53,280 --> 02:05:57,040
PROGENITOR CELLS AND CHONDROCYTE

2941
02:05:57,040 --> 02:06:00,680
EXPANSION, RELEVANT TO THE WORK

2942
02:06:00,680 --> 02:06:06,200
OF IMPLANTATION OR STRUCTURAL

2943
02:06:06,200 --> 02:06:08,240
HYDRA GELS FOR IMPLANTATION AS

2944
02:06:08,240 --> 02:06:12,040
WELL ASTHMA ANYPLACE RATION

2945
02:06:12,040 --> 02:06:13,560
CHONDROCYTE PHENOTYPE INCLUDING

2946
02:06:13,560 --> 02:06:15,560
INHIBITION INFLAMMATION AND

2947
02:06:15,560 --> 02:06:16,960
REGULATION OF CHONDROCYTE

2948
02:06:16,960 --> 02:06:22,000
METABOLISM.  THIS FIGURE WHICH

2949
02:06:22,000 --> 02:06:26,720
IS TAKEN FROM THEIR PAPER SHOWS

2950
02:06:26,720 --> 02:06:30,480
WAYS OF DIFFERENTIATING

2951
02:06:30,480 --> 02:06:33,440
PLURIPOTENTIAL STEM CELLS Z,

2952
02:06:33,440 --> 02:06:38,760
MESENCHYMAL STEM CELLS, STROMAL

2953
02:06:38,760 --> 02:06:40,560
CELLS, TRANSDIFFERENTIATING

2954
02:06:40,560 --> 02:06:43,600
FIBROBLASTS IN FUNCTIONAL

2955
02:06:43,600 --> 02:06:44,480
CHONDROCYTES WITH SMALL MOLECULE

2956
02:06:44,480 --> 02:06:49,120
WHICH IS ARE LISTED ON THE

2957
02:06:49,120 --> 02:06:51,440
SLIDE. AS WELL AS POTENTIAL ROLE

2958
02:06:51,440 --> 02:06:57,720
OF STAT STATINS FROM ISOLATED

2959
02:06:57,720 --> 02:06:58,960
CHONDROCYTES TO CAUSE EXPANSION

2960
02:06:58,960 --> 02:07:00,640
FORMING FUNCTIONAL CHONDROCYTES

2961
02:07:00,640 --> 02:07:04,920
WHICH CAN BE THEN USED FOR CELL

2962
02:07:04,920 --> 02:07:08,120
THERAPY DESCRIBED BY DR. RODEO

2963
02:07:08,120 --> 02:07:09,800
AND AS DISCUSSED BY OTHERS

2964
02:07:09,800 --> 02:07:20,280
DURING AFTER THE BREAK.  THIS

2965
02:07:21,480 --> 02:07:23,000
GROUP ALSO IN THE SECOND PART OF

2966
02:07:23,000 --> 02:07:26,120
THEIR PAPER, SUMMARIZE DATA ON

2967
02:07:26,120 --> 02:07:30,200
MORE THAN 170 COMPOUNDS

2968
02:07:30,200 --> 02:07:31,680
PREVIOUSLY OR CURRENTLY UNDER

2969
02:07:31,680 --> 02:07:35,640
INVESTIGATION. IN PRE-CLINICAL

2970
02:07:35,640 --> 02:07:38,280
MODELS AS ANALGESIC AGENTS OR

2971
02:07:38,280 --> 02:07:41,480
POTENTIAL DISEASE MODIFYING

2972
02:07:41,480 --> 02:07:44,480
OSTEOARTHRITIS DRUGS DESIGNED TO

2973
02:07:44,480 --> 02:07:46,040
INHIBIT STRUCTURAL PROGRESSION

2974
02:07:46,040 --> 02:07:53,840
VIA ANTI-CATABOLIC PATHWAYS, OR

2975
02:07:53,840 --> 02:07:55,960
ANTI-INFLAMMATORY PATHWAYS.

2976
02:07:55,960 --> 02:07:58,160
DISAPPOINTINGLY THESE AUTHORS

2977
02:07:58,160 --> 02:08:00,040
CONCLUDED THAT NONE HAVE HAD A

2978
02:08:00,040 --> 02:08:03,680
SIGNIFICANT LONG TERM EFFECT IN

2979
02:08:03,680 --> 02:08:10,040
PRE-CLINICAL MODELS.  NONE

2980
02:08:10,040 --> 02:08:19,920
EFFECTIVE IN HUMAN STUDIES.  SO

2981
02:08:19,920 --> 02:08:21,480
WHERE DOES IT TAKE US? THESE

2982
02:08:21,480 --> 02:08:24,480
AUTHORS DESCRIBE WAYS ONE

2983
02:08:24,480 --> 02:08:27,680
SCREENS FORMAL MOLECULES AND

2984
02:08:27,680 --> 02:08:31,560
THEY DESCRIBING A MOSTIC

2985
02:08:31,560 --> 02:08:32,760
METHODOLOGIES OF SCREENING SMALL

2986
02:08:32,760 --> 02:08:35,320
MOLECULES TO SEE IF ONE IDENTIFY

2987
02:08:35,320 --> 02:08:38,200
SMALL MOLECULES WHICH AFFECT

2988
02:08:38,200 --> 02:08:43,120
CHONDROCYTE REPLICATION OR

2989
02:08:43,120 --> 02:08:45,560
PROLIFERATION OR LEADING TO THE

2990
02:08:45,560 --> 02:08:47,240
DEVELOPMENT OF ANABOLIC

2991
02:08:47,240 --> 02:08:55,520
PHENOTYPE. SO SAMIMED, BIOSPLICE

2992
02:08:55,520 --> 02:08:56,640
THERAPEUTICS EMPLOYED THIS

2993
02:08:56,640 --> 02:08:59,760
TECHNOLOGY TO IDENTIFY POTENTIAL

2994
02:08:59,760 --> 02:09:02,080
SMALL MOLECULE WINT SIGNALING

2995
02:09:02,080 --> 02:09:04,640
PATHWAY MODULATORS.  HIGH

2996
02:09:04,640 --> 02:09:09,480
THROUGH PUT SCREENING. IDENTIFY

2997
02:09:09,480 --> 02:09:19,000
ONE COMPOUND SM 0690. 03690. NOW

2998
02:09:19,000 --> 02:09:21,280
CALLED (INAUDIBLE) ADMINISTERED

2999
02:09:21,280 --> 02:09:23,080
AS A SINGULAR INTRAARTICULAR

3000
02:09:23,080 --> 02:09:26,960
INJECTION. STUDIED BY

3001
02:09:26,960 --> 02:09:28,680
(INAUDIBLE) AND COLLEAGUES IN

3002
02:09:28,680 --> 02:09:32,440
OSTEOARTHRITIS CARTILAGE IN 2018

3003
02:09:32,440 --> 02:09:35,760
AND 2019 IN PRE-CLINICAL MODELS

3004
02:09:35,760 --> 02:09:37,680
SHOW THIS COMPOUND REDUCE

3005
02:09:37,680 --> 02:09:40,760
RELEASE MATRIX DEGREE DATING

3006
02:09:40,760 --> 02:09:43,760
ENZYMES AND INFLAMMATORY

3007
02:09:43,760 --> 02:09:46,440
CYTOKINE PRODUCTION SO IT WAS

3008
02:09:46,440 --> 02:09:48,880
ANTI-CATABOLIC AND INCREASED

3009
02:09:48,880 --> 02:09:50,240
ANABOLIC TIFTED OF CHONDROCYTES

3010
02:09:50,240 --> 02:09:52,800
IN VITRO AND IN VIVO IN

3011
02:09:52,800 --> 02:09:54,960
PRE-CLINICAL MODELS OF

3012
02:09:54,960 --> 02:09:57,120
OSTEOARTHRITIS. SO IT WAS

3013
02:09:57,120 --> 02:09:59,440
ANTI-CATABOLIC AS WELL AS

3014
02:09:59,440 --> 02:10:03,120
ANABOLIC AND DEMONSTRATED

3015
02:10:03,120 --> 02:10:07,400
MOLECULAR MECHANISMS WHICH HAD

3016
02:10:07,400 --> 02:10:09,320
THIS PANT CATABOLIC AND ANABOLIC

3017
02:10:09,320 --> 02:10:12,240
EFFECT. SO THIS MOLECULE WAS

3018
02:10:12,240 --> 02:10:15,320
SHOWN TO UPREGULATE WNT

3019
02:10:15,320 --> 02:10:17,440
SIGNALING OR DOWN REGULATE THE

3020
02:10:17,440 --> 02:10:19,240
WNT SIGNALING WHICH CONTRIBUTES

3021
02:10:19,240 --> 02:10:25,960
TO OA PROGRESSION. MODULATE WNT

3022
02:10:25,960 --> 02:10:33,280
SIGNALING TO ANTI-INFLAMMATORIER

3023
02:10:33,280 --> 02:10:35,640
IS SO COLLEAGUES CONDUCTED A

3024
02:10:35,640 --> 02:10:41,880
SERIES OF PHASE 1 AND PHASE 2

3025
02:10:41,880 --> 02:10:44,960
STUDIES AND INTERIA THE I CAN

3026
02:10:44,960 --> 02:10:46,440
LAR INJECTION APPEARED SAFE WELL

3027
02:10:46,440 --> 02:10:48,320
TOLERATED ADMINISTERED AS A

3028
02:10:48,320 --> 02:10:50,120
SINGLE ARTICULAR INJECTION. THE

3029
02:10:50,120 --> 02:10:52,120
PHASE 2 STUDIES DEMONSTRATED

3030
02:10:52,120 --> 02:10:56,000
POTENTIAL THERAPEUTIC DOSE AND

3031
02:10:56,000 --> 02:10:57,920
TARGET POPULATION WITH

3032
02:10:57,920 --> 02:11:00,880
UNILATERAL SYMPTOMATIC KNEE

3033
02:11:00,880 --> 02:11:02,880
OSTEOARTHRITIS MEANING THEY HAVE

3034
02:11:02,880 --> 02:11:05,320
SINGLE JOINT INVOLVEMENT OR

3035
02:11:05,320 --> 02:11:07,600
BILATERAL SYMPTOMATIC KNEE OA

3036
02:11:07,600 --> 02:11:18,120
BUT MORE PAIN IN ONE THAN THE

3037
02:11:19,320 --> 02:11:21,720
OTHER KNEE WITHOUT BIDE SPREAD

3038
02:11:21,720 --> 02:11:23,800
PAIN. INTERARTICULAR INJECTION

3039
02:11:23,800 --> 02:11:28,120
WAS NOT ONLY EFFECTIVE

3040
02:11:28,120 --> 02:11:32,160
SYMPTOMATICALLY BUT ALSO

3041
02:11:32,160 --> 02:11:33,520
UNCREASE THICKNESS BY JOINT

3042
02:11:33,520 --> 02:11:36,520
SPACE WITHSTANDING KNEE

3043
02:11:36,520 --> 02:11:37,760
RADIOGRAPHS SO THE COMPANY IS

3044
02:11:37,760 --> 02:11:43,360
TAKEN THIS INTO PHASE 3 STUDIES

3045
02:11:43,360 --> 02:11:44,800
FOR SYMPTOM IMPROVEMENT AS WELL

3046
02:11:44,800 --> 02:11:46,200
AS STRUCTURE MODIFICATION. THESE

3047
02:11:46,200 --> 02:11:54,200
HAVE BEEN COMPLETED, BUT RESULTS

3048
02:11:54,200 --> 02:11:55,760
ARE PENDING. I LOOKED ON

3049
02:11:55,760 --> 02:11:56,680
CLINICALTRIALS.GOV AND RESULTS

3050
02:11:56,680 --> 02:12:03,760
ARE STILL PENDING. WHAT ABOUT

3051
02:12:03,760 --> 02:12:08,400
OTHER SMALL MOLECULE? THIS IS

3052
02:12:08,400 --> 02:12:13,120
ADEN SCENE. IT SIGNALS THROUGH

3053
02:12:13,120 --> 02:12:15,760
THE 2A RECEPTOR AND ATTENUATES

3054
02:12:15,760 --> 02:12:20,600
THE INFLAMMATORY RESPONSE IN

3055
02:12:20,600 --> 02:12:21,600
CHONDROCYTES BY LEADING TO

3056
02:12:21,600 --> 02:12:23,280
DOWNSTREAM INHIBITION OF NF

3057
02:12:23,280 --> 02:12:25,400
KAPPA B AS WELL AS UPREGULATION

3058
02:12:25,400 --> 02:12:27,280
AND RELEASE OF THE

3059
02:12:27,280 --> 02:12:28,240
ANTI-INFLAMMATORY CYTOKINE THAT

3060
02:12:28,240 --> 02:12:32,920
I MENTIONED EARLIER INTERLEUKIN

3061
02:12:32,920 --> 02:12:35,960
10. ADMINISTRATION OF LIPOSOMAL

3062
02:12:35,960 --> 02:12:42,640
ADEN SCENE WAS FOUND EFFICACIOUS

3063
02:12:42,640 --> 02:12:50,120
IN RODENT AS WELL AS MURINE

3064
02:12:50,120 --> 02:12:52,000
MODELS. THIS IS SHOWN IN TWO

3065
02:12:52,000 --> 02:12:52,920
PAPERS CITED AT THE BOTTOM OF

3066
02:12:52,920 --> 02:13:00,520
THE SLIDE.  ONE BY BEKISZ, OTHER

3067
02:13:00,520 --> 02:13:02,920
BY CAI PUBLISHED IN OBESITY

3068
02:13:02,920 --> 02:13:12,040
REVIEWS THIS YEAR. ADENOSENE IS

3069
02:13:12,040 --> 02:13:14,800
DEVELOPED AS A TREATMENT FOR

3070
02:13:14,800 --> 02:13:15,440
POTENTIAL TREATMENT FOR PATIENTS

3071
02:13:15,440 --> 02:13:22,360
WITH OSTEOARTHRITIS. BY

3072
02:13:22,360 --> 02:13:25,480
INCORPORATION INTO LIPOSOMES AND

3073
02:13:25,480 --> 02:13:27,160
IT IS SHOWN YOU CAN HAVE

3074
02:13:27,160 --> 02:13:30,560
ACTIVATION OF A 2A RECEPTOR BY

3075
02:13:30,560 --> 02:13:33,480
INTERARTICULAR INJECTION OF

3076
02:13:33,480 --> 02:13:36,720
LIPOSOMAL ADENOSINE, IT SLOWED

3077
02:13:36,720 --> 02:13:38,880
OA PROGRESSION IN TWO MODELS OF

3078
02:13:38,880 --> 02:13:42,600
ESTABLISHED OSTEOARTHRITIS. AS

3079
02:13:42,600 --> 02:13:45,560
WELL AS MURINE MODEL OF OBESITY

3080
02:13:45,560 --> 02:13:49,240
INDUCED OSTEOARTHRITIS AND RAT

3081
02:13:49,240 --> 02:13:53,200
MODEL OF POST TRIAL

3082
02:13:53,200 --> 02:13:57,120
OSTEOARTHRITIS. ALTERED TGF B

3083
02:13:57,120 --> 02:13:58,440
ACTIVATION AND POST RECEPTOR

3084
02:13:58,440 --> 02:14:00,040
SIGNALING FOR A PATHWAY

3085
02:14:00,040 --> 02:14:02,000
ASSOCIATED WITH CHONDROCYTE

3086
02:14:02,000 --> 02:14:03,080
HYPERTROPHY AND TERMINAL

3087
02:14:03,080 --> 02:14:04,200
DIFFERENTIATION AND MODULATEDNA

3088
02:14:04,200 --> 02:14:08,280
TO A PATHWAY ASSOCIATED WITH

3089
02:14:08,280 --> 02:14:09,720
CHONDROCYTE PROLIFERATION AND

3090
02:14:09,720 --> 02:14:14,640
MATRIX PRODUCTION. STUDIES HAVE

3091
02:14:14,640 --> 02:14:18,560
BEEN CONDUCTED IN A DOG MODEL OF

3092
02:14:18,560 --> 02:14:20,000
OSTEOARTHRITIS AND NOT YET

3093
02:14:20,000 --> 02:14:23,040
PUBLISHED SO I WON'T PRESENT

3094
02:14:23,040 --> 02:14:26,480
THEM AT THIS FORUM, BUT ANOTHER

3095
02:14:26,480 --> 02:14:29,840
POTENTIAL SMALL MOLECULE WHICH

3096
02:14:29,840 --> 02:14:31,640
MAYBE EVE DA I SHUTS FOR

3097
02:14:31,640 --> 02:14:32,560
CHONDROCYTE PROLIFERATION AND

3098
02:14:32,560 --> 02:14:41,800
REGENERATION. BEING COGNIZANT OF

3099
02:14:41,800 --> 02:14:44,640
THE TIMELY STOP HERE AND THERE

3100
02:14:44,640 --> 02:14:45,920
ARE SMALL NOVEL COMPOUNDS

3101
02:14:45,920 --> 02:14:46,920
IDENTIFIED THROUGH HIGH THROUGH

3102
02:14:46,920 --> 02:14:51,000
PUT SIGNALING AND KNOWN

3103
02:14:51,000 --> 02:14:52,920
MECHANISTIC PATHWAYS WHICH

3104
02:14:52,920 --> 02:14:54,960
TARGET CARTILAGE REGENERATION

3105
02:14:54,960 --> 02:14:58,480
AND THESE HAVE POTENTIAL FOR

3106
02:14:58,480 --> 02:15:00,040
FUNCTION DISEASE MODIFYING DRUGS

3107
02:15:00,040 --> 02:15:05,360
IN PATIENTS WITH OSTEOARTHRITIS

3108
02:15:05,360 --> 02:15:08,280
THERE IS A LONG WAY TO GO TO

3109
02:15:08,280 --> 02:15:10,760
REALIZE THIS AS FUTURE

3110
02:15:10,760 --> 02:15:11,960
TREATMENT. SO I WANT TO THANK

3111
02:15:11,960 --> 02:15:19,160
YOU FOR YOUR ATTENTION. SHOWING

3112
02:15:19,160 --> 02:15:20,880
YOU (INAUDIBLE) HALL HERE FOR

3113
02:15:20,880 --> 02:15:25,880
OVER 200 YEARS, USE FOR MEDICAL

3114
02:15:25,880 --> 02:15:29,400
EDUCATION. HOPEFULLY BEFORE THE

3115
02:15:29,400 --> 02:15:31,560
NEXT CENTURY WE WILL HAVE

3116
02:15:31,560 --> 02:15:34,560
EFFECTIVE SMALL MOLECULE

3117
02:15:34,560 --> 02:15:35,640
TREATMENTS FOR CARTILAGE

3118
02:15:35,640 --> 02:15:36,600
REGENERATION FOR OUR PATIENTS

3119
02:15:36,600 --> 02:15:44,200
WITH OSTEOARTHRITIS.

3120
02:15:44,200 --> 02:15:46,880
>>WONDERFUL TALK. GREAT I
DON'T

3121
02:15:46,880 --> 02:15:47,440
HAVE VIEW. I THINK ABOUT

3122
02:15:47,440 --> 02:15:49,480
CARTILAGE REGENERATION I THINK

3123
02:15:49,480 --> 02:15:56,120
IN THIS WHOLE WEBINAR TODAY OA I

3124
02:15:56,120 --> 02:15:57,960
DICHOTOMIES A IN CARTILAGE

3125
02:15:57,960 --> 02:15:58,840
REGENERATION, AS A DIFFERENT

3126
02:15:58,840 --> 02:16:01,760
GROUP OF PATIENTS, CARTILAGE

3127
02:16:01,760 --> 02:16:04,040
CLINICALLY WE DO THERE SINGLE

3128
02:16:04,040 --> 02:16:07,720
FOCAL CARTILAGE DEFECTS. EARLY

3129
02:16:07,720 --> 02:16:10,400
IN ARTHRITIC KNEE BUT DIFFERENT

3130
02:16:10,400 --> 02:16:13,440
THAN CHANGES IN BONE SHAPE, BONE

3131
02:16:13,440 --> 02:16:16,440
MORPHOLOGY, SYNOVIUM, CARTILAGE

3132
02:16:16,440 --> 02:16:22,480
BONE, NOT AMENABLE TO PER SE

3133
02:16:22,480 --> 02:16:23,080
CURRENT TECHNIQUE REGENERATE

3134
02:16:23,080 --> 02:16:24,040
CARTILAGE IN THE JOINT, THAT'S

3135
02:16:24,040 --> 02:16:26,400
GREAT BUT THINK ABOUT CARTILAGE

3136
02:16:26,400 --> 02:16:29,760
REPAIR REGENERATION FOR SMALLER

3137
02:16:29,760 --> 02:16:31,360
FOCAL EFFECTS WHICH BRINGS I

3138
02:16:31,360 --> 02:16:32,760
THINK THE IMPORTANT NEED FOR

3139
02:16:32,760 --> 02:16:35,520
EARLY IDENTIFICATION. CHRONIC

3140
02:16:35,520 --> 02:16:38,480
WORK WITH IMAGING WE ALL

3141
02:16:38,480 --> 02:16:39,600
RECOGNIZE WE NEED BETTER WAYS TO

3142
02:16:39,600 --> 02:16:42,560
IDENTIFY THE PATHOLOGY ONCE

3143
02:16:42,560 --> 02:16:44,200
STRUCTURAL CHANGES IN THE JOINT

3144
02:16:44,200 --> 02:16:46,840
BIGGER CHALLENGE IS STRUCTURAL

3145
02:16:46,840 --> 02:16:48,840
CHANGES CLINICALLY SILENT.

3146
02:16:48,840 --> 02:16:52,480
EARLIER EXAMPLE HEART ATTACK, OR

3147
02:16:52,480 --> 02:16:54,800
THE DIABETIC PATIENT, THE EARLY

3148
02:16:54,800 --> 02:16:56,920
PATHOLOGY IS CLINICALLY SILENT

3149
02:16:56,920 --> 02:16:59,640
TIME WE DETECT END STAGE ORGAN

3150
02:16:59,640 --> 02:17:01,360
DISEASE, THE COW IS OUT OF THE

3151
02:17:01,360 --> 02:17:02,920
BARN. JUST A POINT FOR THE NEED

3152
02:17:02,920 --> 02:17:06,160
FOR EARLY DIAGNOSIS. SO

3153
02:17:06,160 --> 02:17:06,640
REGENERATE TISSUE.

3154
02:17:06,640 --> 02:17:09,320
>>I WOULD FULLY AGREE
WITH YOU.

3155
02:17:09,320 --> 02:17:11,240
AND I THINK THAT'S WHY WE NEED

3156
02:17:11,240 --> 02:17:17,000
TO IDENTIFY PEOPLE WHO DON'T

3157
02:17:17,000 --> 02:17:18,840
HAVE ALREADY ESTABLISHED GRADE

3158
02:17:18,840 --> 02:17:21,040
3, 4 OR EVEN STAGE 2 DISEASE. WE

3159
02:17:21,040 --> 02:17:26,200
NEED TO IDENTIFY PEOPLE WHO HAVE

3160
02:17:26,200 --> 02:17:28,440
SYMPTOMS. DON'T AS YET HAVE

3161
02:17:28,440 --> 02:17:33,480
RADIOGRAPHIC CHANGE. BUT MAY

3162
02:17:33,480 --> 02:17:34,720
HAVE CHANGES ON MAGNETIC

3163
02:17:34,720 --> 02:17:39,560
RESONANCE IMAGING. INTERVENING

3164
02:17:39,560 --> 02:17:42,680
THERE TO TRY TO PREVENT

3165
02:17:42,680 --> 02:17:43,560
DEVELOPMENT OF THE STRUCTURAL

3166
02:17:43,560 --> 02:17:47,440
CHANGES WE SEE ON RADIOGRAPHS.  

3167
02:17:47,440 --> 02:17:48,200
ONCE WE HAVE STRUCTURAL CHANGES

3168
02:17:48,200 --> 02:17:52,920
ON RADIOGRAPH, PARTICULARLY ONCE

3169
02:17:52,920 --> 02:17:55,480
WE HAVE JOINT SPACE NARROWING ON

3170
02:17:55,480 --> 02:17:58,400
THE RADIOGRAPH AND WE HAVE

3171
02:17:58,400 --> 02:17:59,200
SUBCHONDRAL BONE CHANGES, I

3172
02:17:59,200 --> 02:18:04,160
THINK IT IS GOING TO BE VERY

3173
02:18:04,160 --> 02:18:06,000
DIFFICULT UNLESS WE HAVE TWO

3174
02:18:06,000 --> 02:18:09,320
STAGE RESPONSE, ONE WHICH IS

3175
02:18:09,320 --> 02:18:10,480
ANTI-CATABOLIC RESPONSE IN ORDER

3176
02:18:10,480 --> 02:18:14,960
TO PREVENT FURTHER CARTILAGE

3177
02:18:14,960 --> 02:18:16,800
DEGRADATION AND THEN COME IN

3178
02:18:16,800 --> 02:18:18,600
WITH SOMETHING TO PROMOTE

3179
02:18:18,600 --> 02:18:22,200
CARTILAGE REGENERATION.  THAT

3180
02:18:22,200 --> 02:18:24,560
REQUIRES TWO STAGE RESPONSE OR

3181
02:18:24,560 --> 02:18:26,480
TWO STEP RESPONSE UNLIKELY TO

3182
02:18:26,480 --> 02:18:29,320
OCCUR WITH SINGLE SMALL

3183
02:18:29,320 --> 02:18:33,120
MOLECULE. MAY OCCUR WITH GENE

3184
02:18:33,120 --> 02:18:37,680
THERAPY, MAY OCCUR WITH PROTEIN

3185
02:18:37,680 --> 02:18:40,760
THERAPY AND MAY OCCUR WITH STEM

3186
02:18:40,760 --> 02:18:42,560
CELL THERAPY. OR CELLULAR

3187
02:18:42,560 --> 02:18:46,040
THERAPY. BUT IS UNLIKELY I THINK

3188
02:18:46,040 --> 02:18:49,760
TO OCCUR WITH SMALL MOLECULE

3189
02:18:49,760 --> 02:18:50,000
THERAPY.

3190
02:18:50,000 --> 02:18:52,520
>>WHOLE ISSUE I TRIED TO

3191
02:18:52,520 --> 02:18:54,640
HIGHLIGHT SYMPTOM MODIFICATION

3192
02:18:54,640 --> 02:18:56,080
VERSUS STRUCTURE MODIFICATION.

3193
02:18:56,080 --> 02:18:57,040
IMPORTANT GOALS BUT PERHAPS

3194
02:18:57,040 --> 02:19:04,480
DIFFERENT.

3195
02:19:04,480 --> 02:19:07,760
>>AMBIKA HAS HER HAND UP.

3196
02:19:07,760 --> 02:19:11,720
>>THANK YOU FOR THAT TALK
DR.

3197
02:19:11,720 --> 02:19:13,520
HOCHBERG. HOW MANY HUMAN STUDIES

3198
02:19:13,520 --> 02:19:15,560
YOU REFER TO UTILIZE DELIVERY

3199
02:19:15,560 --> 02:19:17,120
SYSTEMS FOR DELIVERING THESE

3200
02:19:17,120 --> 02:19:20,400
SMALL MOLECULES, I ASK THAT

3201
02:19:20,400 --> 02:19:24,600
QUESTION AS SMALL MOLECULES HAVE

3202
02:19:24,600 --> 02:19:26,880
SHORT RESIDENCE TIME INOR INSIDE

3203
02:19:26,880 --> 02:19:29,160
THE JOINT SO THE THE MODE OF

3204
02:19:29,160 --> 02:19:30,480
DELIVERY IS NOT IMPLANTABLE

3205
02:19:30,480 --> 02:19:32,160
INJECTION IT IS DIFFICULT TO GET

3206
02:19:32,160 --> 02:19:34,640
A LONG TERM RESPONSE WITH THESE

3207
02:19:34,640 --> 02:19:36,440
ONE SHOT INJECTIONS

3208
02:19:36,440 --> 02:19:38,720
INTRAOCULARLY. SO WHEN YOU SAY

3209
02:19:38,720 --> 02:19:42,280
THAT MANY -- INTERARTERIOLY,

3210
02:19:42,280 --> 02:19:44,480
WHEN YOU SAW STUDIES DON'T

3211
02:19:44,480 --> 02:19:45,760
CORRELATE WITH PRE-CLINICAL, HOW

3212
02:19:45,760 --> 02:19:47,960
MANY OF THOSE UTILIZE ANY

3213
02:19:47,960 --> 02:19:50,560
DELIVERY SYSTEMS OR WERE THEY

3214
02:19:50,560 --> 02:19:54,440
ONLY DIRECT INJECTION OR ORAL

3215
02:19:54,440 --> 02:19:55,560
INJECTION?

3216
02:19:55,560 --> 02:19:58,440
>>IN THE REVIEW CONDUCTED
THAT

3217
02:19:58,440 --> 02:20:00,520
I CITED, THE SMALL -- MOST OF

3218
02:20:00,520 --> 02:20:03,240
THE SMALL MOLECULE STUDIES WERE

3219
02:20:03,240 --> 02:20:06,120
IN HUMANS, ACTUALLY ORAL SMALL

3220
02:20:06,120 --> 02:20:09,400
MOLECULES ORALLY ADMINISTERED AS

3221
02:20:09,400 --> 02:20:12,320
OPPOSED TO INTERARTICULARLY

3222
02:20:12,320 --> 02:20:14,880
ADMINISTERED. ONCE WE

3223
02:20:14,880 --> 02:20:16,680
INTERARTICULARLY ADMINISTER VERY

3224
02:20:16,680 --> 02:20:18,880
SHORT RESIDENCE TIME AS YOU

3225
02:20:18,880 --> 02:20:20,320
MENTIONED SOME OF THE NEWER

3226
02:20:20,320 --> 02:20:23,600
STUDIES WHICH ARE NOT CITED IN

3227
02:20:23,600 --> 02:20:26,960
THAT PAPER ARE USING FOR

3228
02:20:26,960 --> 02:20:30,480
EXAMPLE, LIPOSOMAL

3229
02:20:30,480 --> 02:20:34,000
ADMINISTRATION OR TRYING TO

3230
02:20:34,000 --> 02:20:36,960
COMBINE THIS WITH HIGH LURE

3231
02:20:36,960 --> 02:20:41,200
ONTIC ACID TO -- HYALURONIC ACID

3232
02:20:41,200 --> 02:20:44,640
TO TAKE ON THE BINDING OF HA TO

3233
02:20:44,640 --> 02:20:46,640
CELL SURFACE RECEPTORS ON THE

3234
02:20:46,640 --> 02:20:48,080
CHONDROCYTE TO GET INTERNALIZED

3235
02:20:48,080 --> 02:20:56,560
BY ENDOCYTOSIS. YOU BRING UP AN

3236
02:20:56,560 --> 02:20:59,400
IMPORTANT POINT ABOUT SHORT

3237
02:20:59,400 --> 02:21:01,160
RESIDENCE SMALL MOLECULES WHEN

3238
02:21:01,160 --> 02:21:02,920
GIVEN BY THEMSELVES

3239
02:21:02,920 --> 02:21:06,200
INTERARTICULARLY. ALSO DELIVERY

3240
02:21:06,200 --> 02:21:09,200
INTO CARTILAGE. WE TARGET SITES

3241
02:21:09,200 --> 02:21:11,440
OR CHONDROCYTES IF WE ENABLE

3242
02:21:11,440 --> 02:21:13,800
LONGER TERM RETENTION THE JOINT

3243
02:21:13,800 --> 02:21:15,200
USING HYALURONIC ACID, WE ARE

3244
02:21:15,200 --> 02:21:17,080
NOT ENSURING DELIVERY TO TISSUE

3245
02:21:17,080 --> 02:21:19,040
TO REACH CHONDROCYTE SO THAT IS

3246
02:21:19,040 --> 02:21:20,880
ANOTHER AREA WHERE DELIVERY IS

3247
02:21:20,880 --> 02:21:22,560
EXTREMELY IMPORTANT FOR ANY OF

3248
02:21:22,560 --> 02:21:25,120
THESE DRUGS TO TRANSLATE.

3249
02:21:25,120 --> 02:21:26,720
>>RIGHT BECAUSE YOU HAVE
TO GET

3250
02:21:26,720 --> 02:21:30,560
DIFFUSION INTO THE MATRIX IN

3251
02:21:30,560 --> 02:21:33,880
ORDER TO APPROACH CHONDROCYTE.

3252
02:21:33,880 --> 02:21:42,800
>>THANK YOU.

3253
02:21:42,800 --> 02:21:44,640
>>I MAY HAVE GOTTEN YOU
CLOSER

3254
02:21:44,640 --> 02:21:49,160
TO ON TIME. 

3255
02:21:49,160 --> 02:21:50,640
>>TED YOU WOULD LIKE TO
TAKE

3256
02:21:50,640 --> 02:21:52,440
OVER AND GIVE INSTRUCTIONS NOW? 

3257
02:21:52,440 --> 02:21:53,880
>>JONELLE?

3258
02:21:53,880 --> 02:21:56,560
>>I CAN DO THAT. THANK
YOU,

3259
02:21:56,560 --> 02:21:58,240
EVERYBODY, THIS WAS A GREAT

3260
02:21:58,240 --> 02:21:59,560
DISCUSSION AND I THINK IT IS

3261
02:21:59,560 --> 02:22:03,200
MORE IMPORTANT THAT WE HAD SUCH

3262
02:22:03,200 --> 02:22:04,560
ROBUST DISCUSSION THAN THAT WE

3263
02:22:04,560 --> 02:22:06,120
STAYED ON TIME. THE DOWN SIDE IS

3264
02:22:06,120 --> 02:22:10,120
WE ARE GOING TO HAVE SHORTER

3265
02:22:10,120 --> 02:22:12,840
TIME FOR LUNCH. AS I SAID

3266
02:22:12,840 --> 02:22:14,520
EARLIER WE WOULD LIKE A GROUP

3267
02:22:14,520 --> 02:22:15,600
PHOTO BEFORE WE BREAK FOR LUNCH

3268
02:22:15,600 --> 02:22:17,800
SO WE HAVE IT FOR OUR ARCHIVES

3269
02:22:17,800 --> 02:22:19,440
AND WHEN WE TALK ABOUT

3270
02:22:19,440 --> 02:22:21,320
IMPORTANCE OF OUR ROUND TABLES

3271
02:22:21,320 --> 02:22:24,280
WE HAVE A VISUAL RATHER THAN A

3272
02:22:24,280 --> 02:22:26,400
TEXT HEAVY SLIDE. IF EVERYBODY

3273
02:22:26,400 --> 02:22:28,680
WHO WANTS TO BE IN THE PICTURE

3274
02:22:28,680 --> 02:22:30,400
INCLUDING NIAMS STAFF WHO ARE

3275
02:22:30,400 --> 02:22:31,520
INVOLVED WOULD LIKE TO TURN ON

3276
02:22:31,520 --> 02:22:34,720
THE CAMERAS, I'M GOING TO ASK

3277
02:22:34,720 --> 02:22:40,200
DAVE TO TAKE A PICTURE.  THEN WE

3278
02:22:40,200 --> 02:22:41,920
CAN START THE CLOCK OFF PICTURE

3279
02:22:41,920 --> 02:22:43,480
FOR 20 MINUTES FOR LUNCH.  

3280
02:22:43,480 --> 02:22:48,120
>>OUR NEXT SPEAKER IS

3281
02:22:48,120 --> 02:22:51,360
DAN GRANDE. 

3282
02:22:51,360 --> 02:22:56,320
HE IS DIRECTOR

3283
02:22:56,320 --> 02:23:00,800
ORTHOPEDIC RESEARCH AT THE

3284
02:23:00,800 --> 02:23:01,560
FEINSTEIN MEDICAL RESEARCH PART

3285
02:23:01,560 --> 02:23:02,600
OF THE HOSPITAL SYSTEM IN NEW

3286
02:23:02,600 --> 02:23:05,400
YORK. I THINK WE HAVE HEARD OF

3287
02:23:05,400 --> 02:23:06,560
AUTOLOGOUS CHONDROCYTE

3288
02:23:06,560 --> 02:23:09,040
IMPLANTATION, THE FIRST FDA

3289
02:23:09,040 --> 02:23:12,680
APPROVED CELL PER THINK IN

3290
02:23:12,680 --> 02:23:19,920
ORTHOPEDICS. DAN DID THE

3291
02:23:19,920 --> 02:23:21,160
PRE-CLINICAL STUDY THAT LED TO

3292
02:23:21,160 --> 02:23:22,400
THAT BREAK THROUGH. SO WE ARE

3293
02:23:22,400 --> 02:23:23,440
PLEASED HE COULD TALK TO US

3294
02:23:23,440 --> 02:23:26,080
ABOUT MATRIX BASED THERAPIES IN

3295
02:23:26,080 --> 02:23:36,080
TISSUE ENGINEERED CARTILAGE.

3296
02:23:36,080 --> 02:23:38,760
>>THANK YOU, EVERYONE.
THANK

3297
02:23:38,760 --> 02:23:41,400
YOU CONNIE FOR THE KIND

3298
02:23:41,400 --> 02:23:44,960
INTRODUCTION. I WILL FOCUS VERY

3299
02:23:44,960 --> 02:23:49,040
NARROW AREA WHICH IS THIS

3300
02:23:49,040 --> 02:23:50,920
CONCEPT OF MY TRICKS BASED

3301
02:23:50,920 --> 02:23:56,280
THERAPIES AND TISSUE ENGINEERED

3302
02:23:56,280 --> 02:23:58,520
CARTILAGE.  THIS IS A VIN

3303
02:23:58,520 --> 02:24:01,720
DIAGRAM WE DID YEARS AGO WITH --

3304
02:24:01,720 --> 02:24:03,520
FOR THE NATURE REVIEW

3305
02:24:03,520 --> 02:24:05,840
RHEUMATOLOGY ARTICLE THAT I

3306
02:24:05,840 --> 02:24:08,560
WROTE WITH MYCOLOGS AND

3307
02:24:08,560 --> 02:24:13,040
BASICALLY THIS COMBINATION OF

3308
02:24:13,040 --> 02:24:16,600
SCAFFOLDS AND CELLS AND THEIR

3309
02:24:16,600 --> 02:24:17,800
INTERACTION WITH TISSUE

3310
02:24:17,800 --> 02:24:20,680
ENGINEERING AS YOU CAN SEE,

3311
02:24:20,680 --> 02:24:23,960
THESE DIFFERENT CELL DIFFERENT

3312
02:24:23,960 --> 02:24:25,600
SCAFFOLD TYPES, ET CETERA. THE

3313
02:24:25,600 --> 02:24:27,280
FIRST TISSUE ENGINEERING WAS

3314
02:24:27,280 --> 02:24:30,080
DEVELOPED BY LANGER WHERE THEY

3315
02:24:30,080 --> 02:24:35,600
USE PGA SUTURES AND CHONDROCYTES

3316
02:24:35,600 --> 02:24:38,480
AND YOU CAN SEE ON THE RIGHT A

3317
02:24:38,480 --> 02:24:39,760
NICE ME IN THIS CUSS OUT OF

3318
02:24:39,760 --> 02:24:41,360
THAT, THAT WAS THE FIRST STEP

3319
02:24:41,360 --> 02:24:44,360
TOWARD TISSUE CARTILAGE

3320
02:24:44,360 --> 02:24:46,240
ENGINEERING, WE WILL TALK ABOUT

3321
02:24:46,240 --> 02:24:49,600
ACI IN A FEW MINUTES BUT THE

3322
02:24:49,600 --> 02:24:52,640
UTILITY OF SCAFFOLD TISSUE

3323
02:24:52,640 --> 02:24:54,800
ENGINEERING IS THAT IT PROVIDES

3324
02:24:54,800 --> 02:24:59,440
A 3-D SPATIAL FILLING SURGEON

3325
02:24:59,440 --> 02:25:02,280
FRIENDLY WITH RESPECT TO BEING

3326
02:25:02,280 --> 02:25:05,480
ABLE TO IMPLANT CELLS IN A

3327
02:25:05,480 --> 02:25:06,240
CONTROLLED FASHION COMPARED TO

3328
02:25:06,240 --> 02:25:08,120
THE ORIGINAL AC I. THIS OF

3329
02:25:08,120 --> 02:25:11,920
COURSE LED TO MANY STUDIES

3330
02:25:11,920 --> 02:25:15,720
LOOKING AT PGA PLA PLGA

3331
02:25:15,720 --> 02:25:16,840
CONSTRUCTS, HERE IS SOMETHING

3332
02:25:16,840 --> 02:25:20,360
FROM A WORK WITH LISA FRIED

3333
02:25:20,360 --> 02:25:21,800
HARVARD YEARS AGO BUT THE

3334
02:25:21,800 --> 02:25:26,880
IMPORTANT THINGS IS THAT FORMING

3335
02:25:26,880 --> 02:25:28,760
STABLE CARTILAGE HELPS REDUCING

3336
02:25:28,760 --> 02:25:31,520
FIBROUS OR VASCULAR INFILTRATION

3337
02:25:31,520 --> 02:25:33,440
INTO A CARTILAGE CONSTRUCT. THAT

3338
02:25:33,440 --> 02:25:36,960
IS VERY IMPORTANT FOR CONTINUITY

3339
02:25:36,960 --> 02:25:38,960
OF CARTILAGE. SOME OF THE

3340
02:25:38,960 --> 02:25:41,400
CONCEPTS FOR CELL BASED

3341
02:25:41,400 --> 02:25:44,520
THERAPIES INVOLVE IDENTIFYING

3342
02:25:44,520 --> 02:25:47,560
SOURCES OF CELLS, WHETHER WE USE

3343
02:25:47,560 --> 02:25:50,760
PRIMARY AUTOLOGOUS CHONDROCYTES

3344
02:25:50,760 --> 02:25:53,840
SORRY FOR MISSPELLING, BONE

3345
02:25:53,840 --> 02:25:56,200
MARROW OR LIPO ASPIRATE STEM

3346
02:25:56,200 --> 02:25:58,080
CELLS. THEY REQUIRE EXPANSION, A

3347
02:25:58,080 --> 02:26:00,760
METHOD RETAINING IN SITU AND

3348
02:26:00,760 --> 02:26:04,720
THEN THE PHENOTYPIC STATE

3349
02:26:04,720 --> 02:26:06,360
CHONDROGENNIC EFFECT HOW THEY

3350
02:26:06,360 --> 02:26:07,920
FORM OR DIRECT FUNCTIONAL TISSUE

3351
02:26:07,920 --> 02:26:11,880
FORMATION.  AS CONNIE MENTIONED

3352
02:26:11,880 --> 02:26:13,120
HEARSAY THE ORIGINAL WORK THAT

3353
02:26:13,120 --> 02:26:19,200
WE DID IN ACI WAS CHONDROCYTES

3354
02:26:19,200 --> 02:26:21,720
SUSPENSION BUT HELD IN PLACE BY

3355
02:26:21,720 --> 02:26:22,560
PERIOUTSIDE YUM SO THERE WAS NO

3356
02:26:22,560 --> 02:26:25,360
-- DEVELOPED FOR CHONDRAL

3357
02:26:25,360 --> 02:26:27,880
LESIONS ALONE NOT'S CENTRAL

3358
02:26:27,880 --> 02:26:32,240
CHONDRAL NECESSARILY, THEY ARE

3359
02:26:32,240 --> 02:26:35,640
SUSPENDED WITH THAT. OF COURSE

3360
02:26:35,640 --> 02:26:37,840
THE NEXT GENERATION WHICH

3361
02:26:37,840 --> 02:26:39,720
ASSISTED IN THE CONCEPT OF

3362
02:26:39,720 --> 02:26:42,400
TISSUE ENGINEER CARTILAGE MATRIX

3363
02:26:42,400 --> 02:26:44,920
ASSISTED ACI WHERE WE GROW THE

3364
02:26:44,920 --> 02:26:48,760
CELLS ON A SCAFFOLD, COLLAGEN

3365
02:26:48,760 --> 02:26:50,920
SCAFFOLD FOR LOCALIZATION WITHIN

3366
02:26:50,920 --> 02:26:54,520
A DEFECT. NEXT GENERATION OF

3367
02:26:54,520 --> 02:26:58,760
THAT IS SOMETHING DEVELOPED BY

3368
02:26:58,760 --> 02:27:00,080
NOVACART 3-D, IT IS THE SAME

3369
02:27:00,080 --> 02:27:04,040
CONCEPT OF ACI BUT THEY ARE

3370
02:27:04,040 --> 02:27:06,720
ALLOWED TO BE EXPANDED MINIMALLY

3371
02:27:06,720 --> 02:27:09,120
AND THEY USE A DIFFERENT

3372
02:27:09,120 --> 02:27:11,240
MATERIAL BIPHASIC COLLAGEN

3373
02:27:11,240 --> 02:27:13,040
SCAFFOLD, I WILL SHOW YOU IN A

3374
02:27:13,040 --> 02:27:18,840
MINUTE BUT CURRENTLY U.S.DA FDA

3375
02:27:18,840 --> 02:27:24,320
TRIALS RIGHT NOW U U.S. PHASE 3

3376
02:27:24,320 --> 02:27:27,320
AND THE PRODUCT IS REGULATED AS

3377
02:27:27,320 --> 02:27:34,240
A BIOLOGIC DEVICE IN COMBINATION

3378
02:27:34,240 --> 02:27:36,880
PRODUCT TAKE SMALL BIOPSY OF

3379
02:27:36,880 --> 02:27:38,600
CARTILAGE, EXPAND AND PUT ON A

3380
02:27:38,600 --> 02:27:43,040
SCAFFOLD AND IN A CONTROLLED BUY

3381
02:27:43,040 --> 02:27:45,880
REACTOR SITUATION WHERE YOU GET

3382
02:27:45,880 --> 02:27:48,720
REALLY GOOD REGENERATION OR NOT

3383
02:27:48,720 --> 02:27:51,520
REGENERATION BUT EXPRESSION OF

3384
02:27:51,520 --> 02:27:55,800
THE CHON CRYOGENIC PHENOTYPE.

3385
02:27:55,800 --> 02:28:00,280
YOU CAN SEE HERE THIS IS THE

3386
02:28:00,280 --> 02:28:01,880
MEME PAIN USED BY THEM, IT IS IN

3387
02:28:01,880 --> 02:28:04,200
THE -- MEMBRANE, IT IS A

3388
02:28:04,200 --> 02:28:08,800
BIPHASIC SCAFFOLD THAT HAS A LOT

3389
02:28:08,800 --> 02:28:11,200
OF PROPERTIES DIFFERENT FROM ALL

3390
02:28:11,200 --> 02:28:13,600
THE OTHER AVAILABLE SCAFFOLDS

3391
02:28:13,600 --> 02:28:15,960
WITH REGARDS TO -- WITH REGARDS

3392
02:28:15,960 --> 02:28:18,040
TO COLLAGEN. YOU CAN SEE ALSO

3393
02:28:18,040 --> 02:28:20,840
THAT THEY GET GOOD INFILTRATION

3394
02:28:20,840 --> 02:28:22,640
OF THE CHONDROCYTES INTO THE

3395
02:28:22,640 --> 02:28:25,800
SCAFFOLD.  THE WAY THAT THE

3396
02:28:25,800 --> 02:28:29,040
SCAFFOLD IS -- AS THEY PURPORTED

3397
02:28:29,040 --> 02:28:34,520
TO BE THAT HAS BETTER PHENOTYPIC

3398
02:28:34,520 --> 02:28:36,720
EXPRESSION MORE AGGREGATE

3399
02:28:36,720 --> 02:28:38,920
SYNTHESIS THAN MONOLAYER CULTURE

3400
02:28:38,920 --> 02:28:40,480
AND COMPARED TO SOME OF THEIR

3401
02:28:40,480 --> 02:28:45,600
COMPETITORS. THIS IS A -- FROM

3402
02:28:45,600 --> 02:28:47,360
THEIR PRODUCT YOU CAN SEE THEY

3403
02:28:47,360 --> 02:28:50,640
HAVE VERY GOOD TYPE 2 STAINING,

3404
02:28:50,640 --> 02:28:54,960
THEY HAVE GOOD STABBING WITH

3405
02:28:54,960 --> 02:28:57,160
DMMD, CLINICAL EVIDENCE ON

3406
02:28:57,160 --> 02:29:00,160
ARTHROSCOPY AND BIOPSY SHOWS

3407
02:29:00,160 --> 02:29:03,320
DECENT CARTILAGE REPAIR

3408
02:29:03,320 --> 02:29:06,520
CARTILAGE WITH EXPRESSION OF

3409
02:29:06,520 --> 02:29:10,640
TYPE 2 COLLAGEN, AND AGRICAN AND

3410
02:29:10,640 --> 02:29:12,440
NICE RESURFACING. SO T A THE END

3411
02:29:12,440 --> 02:29:15,400
OF THE DAY THEY PROVIDE CLINICAL

3412
02:29:15,400 --> 02:29:18,080
EVIDENCE FOR IMPROVED PAIN AND

3413
02:29:18,080 --> 02:29:20,080
FUNCTION AND BOTH RETROSPECTIVE

3414
02:29:20,080 --> 02:29:23,600
STUDY THEY DID AS WELL AS

3415
02:29:23,600 --> 02:29:29,560
PROSPECTIVE STUDY THIS IS TWO

3416
02:29:29,560 --> 02:29:32,080
YEARS FLOW UP. ONE THING DR.

3417
02:29:32,080 --> 02:29:33,520
GUILAK WILL TALK MORE IN DETAIL

3418
02:29:33,520 --> 02:29:35,400
BUT AS I MENTION THESE WERE

3419
02:29:35,400 --> 02:29:39,400
FOCAL DEFECTS, AS DR. ROBEY

3420
02:29:39,400 --> 02:29:40,880
MENTIONED BEFORE THE BREAK,

3421
02:29:40,880 --> 02:29:42,200
FOCAL DEFECTS ARE DIFFERENT

3422
02:29:42,200 --> 02:29:46,440
ANIMAL OR PATIENT RATHER THAN OA

3423
02:29:46,440 --> 02:29:50,760
SO DR. GUILAK DEVELOPED A

3424
02:29:50,760 --> 02:29:54,080
CONCEPT FOR USING BASICALLY

3425
02:29:54,080 --> 02:29:57,560
USING A WOVEN SCAFFOLD MATERIAL,

3426
02:29:57,560 --> 02:30:00,320
RESORBABLE ALSO TO SEED CELLS,

3427
02:30:00,320 --> 02:30:04,080
BE ABLE TO RESURFACE ENTIRE

3428
02:30:04,080 --> 02:30:06,720
DEFECTS ENOUGHS JOE ARTHRITIC

3429
02:30:06,720 --> 02:30:08,960
PATIENTS.  HE WILL TALK NEXT

3430
02:30:08,960 --> 02:30:11,160
LEVEL HE HAS ALREADY DONE FOR --

3431
02:30:11,160 --> 02:30:18,200
WITH THAT CONCEPT. THE NEXT

3432
02:30:18,200 --> 02:30:21,320
GENERATION -- NEXT THING ON THE

3433
02:30:21,320 --> 02:30:24,840
HORIZON IS BIOPRINTING. HERE IS

3434
02:30:24,840 --> 02:30:30,080
WORK WE DID WITH ETH AND ZURECK

3435
02:30:30,080 --> 02:30:35,280
USING A CARTILAGE ECM ADDED TO

3436
02:30:35,280 --> 02:30:37,160
THE BIOLINK. WITH THAT YOU CAN

3437
02:30:37,160 --> 02:30:39,880
DO SOMETHING WE HAVEN'T DONE

3438
02:30:39,880 --> 02:30:43,280
BEFORE TO ACHIEVE ZONAL

3439
02:30:43,280 --> 02:30:45,160
REORGANIZATION THAT HAS BEEN A

3440
02:30:45,160 --> 02:30:47,400
REAL CHALLENGE FOR RESEARCHERS

3441
02:30:47,400 --> 02:30:53,440
IN THIS AREA, HOW TO RECONSTRUCT

3442
02:30:53,440 --> 02:30:55,360
SUPERFICIAL MIDDLE AND DEEP

3443
02:30:55,360 --> 02:30:58,520
ZONES OF CARTILAGE

3444
02:30:58,520 --> 02:31:02,040
RECAPITULATING THAT CAGE, THAT

3445
02:31:02,040 --> 02:31:05,280
IS SOMETHING WE NEED TO DO. AS I

3446
02:31:05,280 --> 02:31:06,920
MENTIONED TISSUE ENGINEERED

3447
02:31:06,920 --> 02:31:10,240
CARTILAGE NEEDS TO INTEGRATE

3448
02:31:10,240 --> 02:31:11,480
WITH SURROUNDING CARTILAGE AS

3449
02:31:11,480 --> 02:31:13,600
WELL AS SUBCHONDRAL BONE,

3450
02:31:13,600 --> 02:31:14,560
MECHANIC A.M. PROPERTIES MATCH

3451
02:31:14,560 --> 02:31:18,920
OF THE ADJACENT TISSUE. 

3452
02:31:18,920 --> 02:31:19,880
ENGINEERING CARTILAGE COPES WITH

3453
02:31:19,880 --> 02:31:21,360
INFLAMMATORY MEDIATOR, THAT

3454
02:31:21,360 --> 02:31:24,560
WOULD BE ELEGANTLY PRESENTED BY

3455
02:31:24,560 --> 02:31:26,800
DR. GUILAK. THE IDEA

3456
02:31:26,800 --> 02:31:28,120
RECAPITULATING THE ZONAL

3457
02:31:28,120 --> 02:31:29,000
ARCHITECTURE OF CARTILAGE IS

3458
02:31:29,000 --> 02:31:33,920
IMPORTANT.  NOW I WILL MOVE TO

3459
02:31:33,920 --> 02:31:35,360
MATRIX BASED APPROACHES TO

3460
02:31:35,360 --> 02:31:40,240
CARTILAGE REPAIR, ONE THAT IS

3461
02:31:40,240 --> 02:31:43,160
VERY NEAR AND DEAR IS AUTOLOGOUS

3462
02:31:43,160 --> 02:31:46,920
MATRIX INDUCED CHONDROGENESIS.

3463
02:31:46,920 --> 02:31:49,280
WE USE THE MICROFRACTURE

3464
02:31:49,280 --> 02:31:51,720
TECHNIQUE TO PLACE A COLLAGEN

3465
02:31:51,720 --> 02:31:54,480
SCAFFOLD IN THE MATRIX, IN THE

3466
02:31:54,480 --> 02:31:59,640
DEFECT. RECENT SYSTEMATIC REVIEW

3467
02:31:59,640 --> 02:32:06,680
LOOKED AT AUTOLOGOUS AMIC VERSUS

3468
02:32:06,680 --> 02:32:09,560
MATRIX ASSISTED ACI. THEY FOUND

3469
02:32:09,560 --> 02:32:12,280
AMIC PERFORMED BETTER FOR THE

3470
02:32:12,280 --> 02:32:15,800
CHONDRAL DEFECTS AT 40 MONTHS.

3471
02:32:15,800 --> 02:32:17,360
THE RATE OF COMPLICATIONS WAS

3472
02:32:17,360 --> 02:32:21,080
LOWER IN THE AMIC GROUP AND

3473
02:32:21,080 --> 02:32:23,520
TEGNER AND VAST SCORES EQUIVOCAL

3474
02:32:23,520 --> 02:32:27,920
BUT LYSOME AND IDKE CELLS

3475
02:32:27,920 --> 02:32:30,480
EXCEEDED THE ACID IN FAVOR OF

3476
02:32:30,480 --> 02:32:31,920
AMIC. THAT IS SOMETHING TO KEEP

3477
02:32:31,920 --> 02:32:39,200
IN MIND WHEN WE TALK ABOUT COST

3478
02:32:39,200 --> 02:32:41,000
BENEFIT RATIO IS FOR SYSTEM OF

3479
02:32:41,000 --> 02:32:45,440
THESE PRODUCTS AND APPROACHES.  

3480
02:32:45,440 --> 02:32:48,840
I DID A EDITORIAL FOR NATURE

3481
02:32:48,840 --> 02:32:50,280
REVIEWS, ON NEWER CONCEPT WHICH

3482
02:32:50,280 --> 02:32:53,160
I THINK HAS A LOT OF PROMISE BUT

3483
02:32:53,160 --> 02:32:54,680
NOT WIDELY DEVELOPED AND THAT IS

3484
02:32:54,680 --> 02:32:59,200
THE CONCEPT OF USING SCAFFOLDS

3485
02:32:59,200 --> 02:33:02,560
WITH LOADED WITH MOLECULES THAT

3486
02:33:02,560 --> 02:33:10,600
WOULD BE ALLOW FOR MIGRATION OR

3487
02:33:10,600 --> 02:33:15,240
ZONAL MIGRATION INTO SCAFFOLD BY

3488
02:33:15,240 --> 02:33:17,320
HOMING. YOU CAN SEE USING THE

3489
02:33:17,320 --> 02:33:19,840
BODY'S OWN ABILITY TO HEAL IN

3490
02:33:19,840 --> 02:33:30,560
THAT CONTEXT. BST CARGEL IS A

3491
02:33:30,560 --> 02:33:33,280
CHITOSAN PRODUCT SIMILAR ARCMIC

3492
02:33:33,280 --> 02:33:34,960
AND ADJUNCT TO MICROFRACTURE AND

3493
02:33:34,960 --> 02:33:37,960
USE BLOOD OR PRP TO COAGULATE OR

3494
02:33:37,960 --> 02:33:40,960
POLYMER RISE THE MATERIALS IN

3495
02:33:40,960 --> 02:33:51,480
VIVO. FILL AS WELL AS CALL OF

3496
02:33:52,040 --> 02:33:57,960
REPAIR, USING T 2 MAPPING MRI.

3497
02:33:57,960 --> 02:34:03,200
BETTER SCORES, MUCH BETTER FILL

3498
02:34:03,200 --> 02:34:09,360
OVERALL. BIOCART LAG IS ANOTHER

3499
02:34:09,360 --> 02:34:13,160
ADJUNCT MATERIAL FOR

3500
02:34:13,160 --> 02:34:15,280
MICROFRACTURE. IT IS ALLOGRAPH,

3501
02:34:15,280 --> 02:34:18,600
DEHYDRATED, MIX WITH PRP. THE

3502
02:34:18,600 --> 02:34:26,440
IDEA IS THAT IT IMPROVES REPIR

3503
02:34:26,440 --> 02:34:29,680
OF TISSUE. YOU HAVE BETTER

3504
02:34:29,680 --> 02:34:31,080
COLLAGEN TYPE 2 FORMATION IN A

3505
02:34:31,080 --> 02:34:35,040
TREATED GROUP.  BASICALLY THE

3506
02:34:35,040 --> 02:34:37,880
OPTIONS FOR CARTILAGE HAVE

3507
02:34:37,880 --> 02:34:39,120
REPAIRED, THAT REMAIN THE SAME

3508
02:34:39,120 --> 02:34:49,680
FOR THE LAST 20 YEARS, ALLOGRAPH

3509
02:34:51,160 --> 02:34:53,280
TRANSPLANTATION. ACI WHICH IS

3510
02:34:53,280 --> 02:34:59,600
MACI, PAL LOW GRAPH,

3511
02:34:59,600 --> 02:35:00,640
PARTICULATED OR MINCED AUTO

3512
02:35:00,640 --> 02:35:02,400
GRAPH. INDICATED FOR FOCAL

3513
02:35:02,400 --> 02:35:06,280
DEFECT BUT OFF LABEL EXPANDED TO

3514
02:35:06,280 --> 02:35:14,360
INCLUDE EARLY OA. MICROFRACTURE

3515
02:35:14,360 --> 02:35:16,800
YIELDS WANING CLINICAL EFFECT

3516
02:35:16,800 --> 02:35:18,520
DUE TO PRODUCTION OF

3517
02:35:18,520 --> 02:35:22,360
FIBROCARTILAGE.  WHILE OTHER

3518
02:35:22,360 --> 02:35:24,560
YIELD OSTEO CHONDRAL ALLOGRAPH

3519
02:35:24,560 --> 02:35:26,560
YIELD HIGH LINK CARTILAGE,

3520
02:35:26,560 --> 02:35:33,640
OTHERS ARE WHAT WE CALL HYALIN

3521
02:35:33,640 --> 02:35:37,560
LIKE AND NOT THE PARTICULAR ARC

3522
02:35:37,560 --> 02:35:39,480
CONNECT CHURL CARTILAGE. WE ALSO

3523
02:35:39,480 --> 02:35:41,920
HAVE TO THINK ABOUT CONUNDRUM,

3524
02:35:41,920 --> 02:35:43,200
CELLS ARE EXPENSIVE SO IF YOU

3525
02:35:43,200 --> 02:35:49,720
HAVE TO DO MACI OR OTHER, THESE

3526
02:35:49,720 --> 02:35:51,720
ARE QUITE EXPENSIVE FOR THE

3527
02:35:51,720 --> 02:35:54,920
PATIENT, THESE -- EVEN IF YOU

3528
02:35:54,920 --> 02:35:59,160
USE ALLOGRAPH THEY ARE 15 TO

3529
02:35:59,160 --> 02:36:09,520
16,000, EXPENSIVE PROPOSITION.  

3530
02:36:09,520 --> 02:36:12,160
THIS MATERIAL FROM ARAGONITE. 

3531
02:36:12,160 --> 02:36:15,720
WE HAVE A LONG HISTORY USING

3532
02:36:15,720 --> 02:36:19,720
CORALS AS A SCAFFOLD FOR BONE

3533
02:36:19,720 --> 02:36:28,160
REPAIR BUT NOT CARTILAGE. SEES

3534
02:36:28,160 --> 02:36:33,400
THIS CONCEPT AS INFLUENCE SIDE

3535
02:36:33,400 --> 02:36:36,640
OF THE POORS INFLUENCE MSC

3536
02:36:36,640 --> 02:36:40,640
DIFFERENTIATION. THEY FOUND THAT

3537
02:36:40,640 --> 02:36:46,120
THIS CONCEPT TO GET GOOD BONE

3538
02:36:46,120 --> 02:36:49,600
HEALING LETS CREATE A BIPHASIC

3539
02:36:49,600 --> 02:36:54,280
IMPLANT BY CREATING FOR'STY AT

3540
02:36:54,280 --> 02:36:57,000
THE CHONDRAL PHASE, LEADING TO

3541
02:36:57,000 --> 02:36:57,600
REGENERATION OF HIGHER END

3542
02:36:57,600 --> 02:36:58,680
CARTILAGE, SO THEY CAME UP WITH

3543
02:36:58,680 --> 02:37:02,400
THIS WAY TO DRILL HOLES OF A

3544
02:37:02,400 --> 02:37:04,960
SPECIFIC PROPRIETARY DIAMETER

3545
02:37:04,960 --> 02:37:09,640
THAT ALLOWS FOR CELLS TO COME UP

3546
02:37:09,640 --> 02:37:13,320
INTO IN A MODEL OF OSTEO

3547
02:37:13,320 --> 02:37:14,200
CHONDRAL DEFECT CELLS COMING UP

3548
02:37:14,200 --> 02:37:16,640
FROM THE MARROW TO BECOME

3549
02:37:16,640 --> 02:37:20,320
CONTRACYTES OR DIFFERENTIATE --

3550
02:37:20,320 --> 02:37:24,640
CHONDROCYTES. SO WORK DONE BY

3551
02:37:24,640 --> 02:37:28,120
SUSAN SKY IN VITRO MODEL TO GET

3552
02:37:28,120 --> 02:37:33,760
MECHANISM OF ACTION, DONUT

3553
02:37:33,760 --> 02:37:39,040
SHAPED HUMAN CART LAG FROM A

3554
02:37:39,040 --> 02:37:42,480
PATIENT -- FROM CADAVER PUT THE

3555
02:37:42,480 --> 02:37:46,240
IMPLANT IN YOU CAN SEE OVER TIME

3556
02:37:46,240 --> 02:37:48,040
NICE CARTILAGE FLOW ENHANCED

3557
02:37:48,040 --> 02:37:51,880
THROUGH DRILL HOLES. YOU CAN SEE

3558
02:37:51,880 --> 02:37:53,600
CHONDROCYTES MIGRATE ACROSS THE

3559
02:37:53,600 --> 02:37:56,560
TYPE OF THE SCAFFOLD AS WELL AS

3560
02:37:56,560 --> 02:38:02,560
FROM UNDERNEATH. THIS IS SHOWING

3561
02:38:02,560 --> 02:38:05,760
STUDIES LIKE TRACING THE CELLS. 

3562
02:38:05,760 --> 02:38:08,320
SO THEY HAVE A MECHANISM OF

3563
02:38:08,320 --> 02:38:12,120
ACTION FOR THAT MATERIAL FOR

3564
02:38:12,120 --> 02:38:15,160
THAT. EVENTUALLY THEY MOVE TO A

3565
02:38:15,160 --> 02:38:16,600
GOAT MODEL, THERE ARE NICE

3566
02:38:16,600 --> 02:38:20,040
COLLAGEN TYPE 2 AND NICE AGRICAN

3567
02:38:20,040 --> 02:38:26,280
FORMATION IN DEFECTS MICROCT

3568
02:38:26,280 --> 02:38:28,800
SHOWING VERY NICE REPAIR OF THE

3569
02:38:28,800 --> 02:38:34,120
SUBCHONDRAL BONE. FIRST IN MAN

3570
02:38:34,120 --> 02:38:37,160
WAS DONE IN EASTERN EUROPE, THEY

3571
02:38:37,160 --> 02:38:40,160
RECEIVED THE 2016 CE MARK AND

3572
02:38:40,160 --> 02:38:42,400
MOVED TO NUMBER OF THINGS. ONCE

3573
02:38:42,400 --> 02:38:46,000
THE FOCAL DEFECT IN PATIENTS ARE

3574
02:38:46,000 --> 02:38:48,360
DOING WELL THEY ADDED PATIENTS

3575
02:38:48,360 --> 02:38:52,840
WITH KL 2 AND 3 DEGENRE ACTIVE

3576
02:38:52,840 --> 02:38:54,400
JOINT DISEASE TO THE MIX. THIS

3577
02:38:54,400 --> 02:39:02,000
IS SHOWING MMRIs, GOOD REPAIR,

3578
02:39:02,000 --> 02:39:03,920
NICE BIOPSY, NICE COLLAGEN TYPE

3579
02:39:03,920 --> 02:39:07,200
2 STAINING AS WELL AS

3580
02:39:07,200 --> 02:39:07,880
(INAUDIBLE) STAINENING THOSE

3581
02:39:07,880 --> 02:39:09,200
PATIENTS.  THE CLINICAL

3582
02:39:09,200 --> 02:39:14,880
EXPERIENCE SO FAR WITH COHORT OF

3583
02:39:14,880 --> 02:39:18,880
126 MAS126 PATIENTS RESULTED INE

3584
02:39:18,880 --> 02:39:20,520
BREAK DOWN OF THE PATIENTS BUT

3585
02:39:20,520 --> 02:39:23,000
THE BOTTOM LINE IS WITH MRI

3586
02:39:23,000 --> 02:39:26,640
RESULTS YOU HAVE A GOOD FILL

3587
02:39:26,640 --> 02:39:30,760
OVER TWO YEARS, THE PRIMARY END

3588
02:39:30,760 --> 02:39:37,880
POINTS FOR THE SCORES ALSO VERY

3589
02:39:37,880 --> 02:39:40,000
GOOD. THESE ARE PATIENTS WITH

3590
02:39:40,000 --> 02:39:46,760
MILD TO MODERATE OA. THIS IS THE

3591
02:39:46,760 --> 02:39:49,520
FIRST DEVICE MATRIX BASED DEVICE

3592
02:39:49,520 --> 02:39:51,600
NOW APPROVED IN THE U.S.

3593
02:39:51,600 --> 02:39:55,240
RECENTLY, APPROVED FOR OA AS

3594
02:39:55,240 --> 02:39:58,920
WELL AS CARTILAGE REPAIR. WHAT I

3595
02:39:58,920 --> 02:40:01,040
WOULD LIKE TO SAY IN SUMMARY, I

3596
02:40:01,040 --> 02:40:03,480
THINK WE NEED TO LOOK AT

3597
02:40:03,480 --> 02:40:07,440
CARTILAGE REPAIR AND OA IN

3598
02:40:07,440 --> 02:40:10,320
GENERAL AS WE NEED TO LOOK AT IT

3599
02:40:10,320 --> 02:40:13,840
AS AN INTEGRATED APPROACH TO HOW

3600
02:40:13,840 --> 02:40:17,360
WE LOOK AT IT, PUTTING IMPLANT

3601
02:40:17,360 --> 02:40:19,920
IN WITHOUT LOOKING AT SAY MMP

3602
02:40:19,920 --> 02:40:24,800
INHIBITOR OR SOME OTHER MOLECULE

3603
02:40:24,800 --> 02:40:27,200
OR IS WRONG WE NEED TO LOOK AT

3604
02:40:27,200 --> 02:40:28,800
THE ENTIRE PICTURE HAVE

3605
02:40:28,800 --> 02:40:31,240
INTEGRATED APPROACH TO CARTILAGE

3606
02:40:31,240 --> 02:40:33,680
REPAIR. WITH THAT, THANK YOU.  I

3607
02:40:33,680 --> 02:40:40,240
APPRECIATE BEING HERE TODAY. 

3608
02:40:40,240 --> 02:40:44,320
>>NICE OVERVIEW, IMPLANT
BRINGS

3609
02:40:44,320 --> 02:40:45,640
UP THE IMPORTANCE OF PAYING

3610
02:40:45,640 --> 02:40:47,200
ATTENTION TO SUBCHONDRAL BONE AS

3611
02:40:47,200 --> 02:40:50,000
WELL, ONE CONCERN OF COROLLARY

3612
02:40:50,000 --> 02:40:52,760
MATERIALS IS SLOW RESORPTION IN

3613
02:40:52,760 --> 02:40:55,040
REMODELING, LOOK AT THEIR DATA,

3614
02:40:55,040 --> 02:40:57,040
BETTER THAN TRADITIONAL CORAL

3615
02:40:57,040 --> 02:40:58,600
STAY AROUND FOREVER AND IS A

3616
02:40:58,600 --> 02:41:00,160
MISMATCH IN YOUR MATERIAL

3617
02:41:00,160 --> 02:41:01,920
PROPERTIES OF THESE MATERIALS

3618
02:41:01,920 --> 02:41:03,480
SUBCHONDRAL BONE SO THAT IS ONE

3619
02:41:03,480 --> 02:41:05,160
CONCERN, JUST A COMMENT COMES UP

3620
02:41:05,160 --> 02:41:07,800
WITH ANY BIPHASIC MATERIALS. THE

3621
02:41:07,800 --> 02:41:10,680
SECOND IS, THIS ISSUE OF

3622
02:41:10,680 --> 02:41:12,680
CARTILAGE REPAIR, OSTEOARTHRITIS

3623
02:41:12,680 --> 02:41:14,320
THAT SLIDE SHOWED A MOMENT AGO

3624
02:41:14,320 --> 02:41:16,200
THE COMPANY CAME TO TALK TO US

3625
02:41:16,200 --> 02:41:18,640
ABOUT IMPLANT, FOUR IMPLANTS,

3626
02:41:18,640 --> 02:41:21,720
MOST OF US AS CLINICIANS, THAT'S

3627
02:41:21,720 --> 02:41:23,240
CALLED OSTEOARTHRITIS. NOT GOING

3628
02:41:23,240 --> 02:41:27,560
TO DO FOUR IMPLANTS. CURIOUS HOW

3629
02:41:27,560 --> 02:41:29,440
FIELD IS EVOLVING LOVE TO FOLLOW

3630
02:41:29,440 --> 02:41:30,720
PATIENTS BECAUSE THAT GETS TO

3631
02:41:30,720 --> 02:41:36,520
THE ISSUE OF PATIENT SEPARATE

3632
02:41:36,520 --> 02:41:38,560
IMPLANT -- DEFECTS YOU ARE

3633
02:41:38,560 --> 02:41:40,880
TREATING, THERE ARE CHANGES IN

3634
02:41:40,880 --> 02:41:44,000
BONE GEOMETRY, REALLY FAVORABLE

3635
02:41:44,000 --> 02:41:46,080
TO HEALING REMODELING, I DON'T

3636
02:41:46,080 --> 02:41:48,200
KNOW. THOSE ARE -- COME UP

3637
02:41:48,200 --> 02:41:49,720
VERSUS USING THESE THINGS FOR

3638
02:41:49,720 --> 02:41:52,840
MORE TYPICAL SINGLE FOCAL

3639
02:41:52,840 --> 02:41:56,000
CHONDRAL DEFECT. 

3640
02:41:56,000 --> 02:41:58,240
>>THANK YOU, DAN, I WANT
TO

3641
02:41:58,240 --> 02:42:00,400
FOLLOW-UP ON THAT, THE

3642
02:42:00,400 --> 02:42:02,320
RADIOGRAPHIC CRITERIA, I BELIEVE

3643
02:42:02,320 --> 02:42:05,880
YOU SAID WAS KL 2 TO 3.

3644
02:42:05,880 --> 02:42:08,640
>>YES.

3645
02:42:08,640 --> 02:42:12,480
>>THERE WERE ABOUT
HUNDRED PLUS

3646
02:42:12,480 --> 02:42:15,240
PATIENTS TREATED.

3647
02:42:15,240 --> 02:42:16,280
>>124.

3648
02:42:16,280 --> 02:42:18,840
>>CAN YOU GO MORE IN
DETAIL ON

3649
02:42:18,840 --> 02:42:24,320
THE OUTCOMES OF THAT ARM OF THE

3650
02:42:24,320 --> 02:42:25,920
STUDY? THOSE ARE ARTHRITIC

3651
02:42:25,920 --> 02:42:29,600
KNEES.  RAID YES GRAPHIC GENE.

3652
02:42:29,600 --> 02:42:34,160
>>ACTUALLY KEN MY
COLLEAGUE DID

3653
02:42:34,160 --> 02:42:36,800
THAT STUDY. ON BEING

3654
02:42:36,800 --> 02:42:39,880
NON-CLINICIAN. I DON'T HAVE

3655
02:42:39,880 --> 02:42:40,800
UNFORTUNATELY MORE DATA ON THAT.

3656
02:42:40,800 --> 02:42:48,240
I'M SORRY. DEMONSTRATE GOOD

3657
02:42:48,240 --> 02:42:51,560
OUTCOMES CLINICAL PROMs AS DAN

3658
02:42:51,560 --> 02:42:55,200
SHOWED THEM. WE HAVE THE SAME

3659
02:42:55,200 --> 02:42:56,720
TREATING MULTIPLE DEFECTS MANY

3660
02:42:56,720 --> 02:43:00,760
THE KNEE, WE TRULY REGENERATE

3661
02:43:00,760 --> 02:43:02,680
CARTILAGE AND THAT HARSH

3662
02:43:02,680 --> 02:43:03,400
ENVIRONMENT, MOB WE WOULD LIKE

3663
02:43:03,400 --> 02:43:05,880
TO, I DON'T KNOW THE ANSWER.

3664
02:43:05,880 --> 02:43:10,320
>>I AGREE WITH YOU, IT IS
A

3665
02:43:10,320 --> 02:43:12,880
FIRST STEP IN THAT DIRECTION.

3666
02:43:12,880 --> 02:43:15,520
CERTAINLY THE FACT THAT THEY

3667
02:43:15,520 --> 02:43:19,680
HAVE GOTTEN APPROVAL FOR OA IS

3668
02:43:19,680 --> 02:43:28,280
THEY CONVINCE THE FDA. DR.

3669
02:43:28,280 --> 02:43:32,400
LATTERMANN HAS A QUESTION.

3670
02:43:32,400 --> 02:43:33,720
>>I CAN ANSWER THAT, I
WAS

3671
02:43:33,720 --> 02:43:39,360
INVOLVED IN THIS STUDY.  AND I

3672
02:43:39,360 --> 02:43:40,560
HAD ONE PATIENT I PLANTED FIVE

3673
02:43:40,560 --> 02:43:46,160
OF THESE.  WHO RELIABLY FAILED.

3674
02:43:46,160 --> 02:43:47,920
ONCE YOU START PUTTING MORE THAN

3675
02:43:47,920 --> 02:43:50,320
TWO IN, TWO OF THESE IMPLANTS

3676
02:43:50,320 --> 02:43:55,360
IN, FAILURE RATE IS HIGH.  UP TO

3677
02:43:55,360 --> 02:43:57,840
TWO IMPLANTS EVEN IN KO 3

3678
02:43:57,840 --> 02:43:59,040
CLASSIFIED X-RAYS, THEY DID VERY

3679
02:43:59,040 --> 02:44:04,880
WELL.  THIS IS ONE OF THOSE

3680
02:44:04,880 --> 02:44:08,200
SUBGROUPS LOOKS LIKE KL 3 AND WE

3681
02:44:08,200 --> 02:44:09,720
KNOW HOW DIFFICULT THAT IS TO

3682
02:44:09,720 --> 02:44:13,240
DIFFERENTIATE, SAY A TWO OR

3683
02:44:13,240 --> 02:44:17,320
SOMETIMES A 1. CLINICALLY THEY

3684
02:44:17,320 --> 02:44:21,800
ACTUALLY NOT THAT HARD TO ARREST

3685
02:44:21,800 --> 02:44:23,600
IS THAT. THAT IS A CONSIDERATION

3686
02:44:23,600 --> 02:44:25,600
TO YES EARLY OA. IT WORKS IN

3687
02:44:25,600 --> 02:44:29,320
THOSE PATIENTS, ESTABLISHED OA

3688
02:44:29,320 --> 02:44:33,840
STILL GOING TO BE A CHALLENGE.  

3689
02:44:33,840 --> 02:44:36,800
ITCH ANOTHER COMMENT, THAT IS

3690
02:44:36,800 --> 02:44:38,240
FOR YEARS WE HAVE HAD DIFFERENT

3691
02:44:38,240 --> 02:44:42,160
TECHNIQUES AND TECHNOLOGIES THAT

3692
02:44:42,160 --> 02:44:43,520
ARE SUCCESSFUL IN TREATING

3693
02:44:43,520 --> 02:44:45,480
CARTILAGE DEFECTS.  WE HAVE A

3694
02:44:45,480 --> 02:44:49,880
FEW THE ACI FOR OVER 20 YEARS WE

3695
02:44:49,880 --> 02:44:52,400
HAVE OSTEO CHONDRAL LOW GRAPH,

3696
02:44:52,400 --> 02:44:54,320
WE CAN TREAT CARTILAGE DEFECTS

3697
02:44:54,320 --> 02:44:55,800
WHAT WE CAN'T TREAT IS

3698
02:44:55,800 --> 02:44:57,080
PROGRESSION OF DISEASE. THAT IS

3699
02:44:57,080 --> 02:44:58,520
WHAT WE NEED TO FIGURE OUT AND I

3700
02:44:58,520 --> 02:45:00,840
THINK THAT'S WHAT WE NEED TO --

3701
02:45:00,840 --> 02:45:04,200
WHAT WE NEED TO FOCUS ON. WE ARE

3702
02:45:04,200 --> 02:45:07,680
TALKING ABOUT EARLY

3703
02:45:07,680 --> 02:45:09,240
OSTEOARTHRITIS BECAUSE CARTILAGE

3704
02:45:09,240 --> 02:45:16,120
IS A CASUALTY. WE HAVE

3705
02:45:16,120 --> 02:45:17,360
EXPERIENCE ALL TIME AND SURGEONS

3706
02:45:17,360 --> 02:45:20,400
ON THE CALL KNOW THAT, IT IS

3707
02:45:20,400 --> 02:45:23,400
EXTRAORDINARILY DIFFICULT TO

3708
02:45:23,400 --> 02:45:24,840
PATIENT EVEN IF YOU GO WITH

3709
02:45:24,840 --> 02:45:28,400
ULTRA SCOPE WHO IS AT THAT

3710
02:45:28,400 --> 02:45:35,640
JUNCTION BETWEEN 1 TO 2 CHONDRAL

3711
02:45:35,640 --> 02:45:36,880
CHANGES, WHERE YOU SAY IT IS NOT

3712
02:45:36,880 --> 02:45:38,960
BAD ENOUGH TO DO -- AND THERE'S

3713
02:45:38,960 --> 02:45:40,120
ONE FOCAL LESION. IF YOU TREAT

3714
02:45:40,120 --> 02:45:42,120
THE FOCAL LESION YOU GO BACK

3715
02:45:42,120 --> 02:45:44,320
ISN'T TWO YEARS LATER AND THAT

3716
02:45:44,320 --> 02:45:45,480
FOCAL LESION LOOKS BEAUTIFUL AND

3717
02:45:45,480 --> 02:45:47,880
THE REST OF THE JOINT IS BROKEN

3718
02:45:47,880 --> 02:45:49,200
DOWN. THAT'S THE TYPE OF PATIENT

3719
02:45:49,200 --> 02:45:52,960
WE NEED TO IDENTIFY. AND TREAT

3720
02:45:52,960 --> 02:45:54,960
DIFFERENTLY. THAT'S THE PATIENT

3721
02:45:54,960 --> 02:45:57,040
THAT IS ON THE PAST

3722
02:45:57,040 --> 02:45:58,600
OSTEOARTHRITIS AND THAT IS

3723
02:45:58,600 --> 02:46:01,600
BASICALLY WHAT WE NEED TO STUDY 

3724
02:46:01,600 --> 02:46:03,640
>>THAT BRINGS UP THE
QUESTION

3725
02:46:03,640 --> 02:46:05,960
OF HOW DO WE STAGE THOSE

3726
02:46:05,960 --> 02:46:08,280
PATIENTS AND WHAT MARKERS CAN BE

3727
02:46:08,280 --> 02:46:11,320
USED BECAUSE WE DON'T HAVE GOOD

3728
02:46:11,320 --> 02:46:17,280
MARKERS FOR EARLY OA YET. DO WE 

3729
02:46:17,280 --> 02:46:22,320
>>THE BIG SEARCH, YOU CAN
-- IT

3730
02:46:22,320 --> 02:46:24,560
IS NOT GOING TO BE -- I THINK IT

3731
02:46:24,560 --> 02:46:28,560
NEEDS TO BE A COMBINATION OF

3732
02:46:28,560 --> 02:46:34,200
IMAGING AND MOLECULAR MARKERS

3733
02:46:34,200 --> 02:46:38,480
AND POSSIBLY SYSTEMIC MARKERS WE

3734
02:46:38,480 --> 02:46:41,240
ALL HAVE PATIENTS THAT JUST GO

3735
02:46:41,240 --> 02:46:43,280
ALONG GO ALONG AND ONE DAY IT IS

3736
02:46:43,280 --> 02:46:46,040
LIKE SOMETHING SWITCHED. AND HOW

3737
02:46:46,040 --> 02:46:47,600
YOU CAN NO LONGER MANAGE THEIR

3738
02:46:47,600 --> 02:46:52,560
DISEASE OR THEY GO INTO PHASE OF

3739
02:46:52,560 --> 02:46:55,880
RAPID PROGRESSION. THOSE ARE

3740
02:46:55,880 --> 02:46:59,040
SWITCHES.  THIS IS ONE OF THE

3741
02:46:59,040 --> 02:47:04,000
RESEARCH NEEDS, WHAT ARE THE HOW

3742
02:47:04,000 --> 02:47:08,280
DO WE SUBTYPE OA DO A BETTER JOB

3743
02:47:08,280 --> 02:47:10,360
STRUCTURALLY THAN LAWRENCE WHICH

3744
02:47:10,360 --> 02:47:13,960
WAS DEVELOPED IN THE 50s,

3745
02:47:13,960 --> 02:47:18,840
1950s. AND YOU HAVE PATIENTS

3746
02:47:18,840 --> 02:47:20,240
THAT HAVE OSTEO DIET BUS STILL

3747
02:47:20,240 --> 02:47:22,360
HAVE A JOINT SPACE AND OTHER

3748
02:47:22,360 --> 02:47:30,600
WHOSE HAVE NO OSTEOCYTES BUT

3749
02:47:30,600 --> 02:47:31,560
THEY HAVE CHONDRAL FLATTENING.

3750
02:47:31,560 --> 02:47:33,280
SO THE GRADING NEEDS TO BE

3751
02:47:33,280 --> 02:47:34,800
BETTER STRUCTURALLY AND ALSO

3752
02:47:34,800 --> 02:47:36,360
INCLUDE MECHANICAL AND

3753
02:47:36,360 --> 02:47:40,000
BIOLOGICAL AND MOLECULAR

3754
02:47:40,000 --> 02:47:44,440
PROFILING IN TO THE ALGORITHM.

3755
02:47:44,440 --> 02:47:47,960
>>WHAT WE CALL
OSTEOARTHRITIS

3756
02:47:47,960 --> 02:47:49,280
IS 25 DIFFERENT CONDITIONS.

3757
02:47:49,280 --> 02:47:54,920
>>MAYBE MORE THAN THAT.
AT

3758
02:47:54,920 --> 02:47:56,160
LEAST WE CAN SUB CATEGORIZE

3759
02:47:56,160 --> 02:47:59,920
BETTER THAN WE DO NOW. 

3760
02:47:59,920 --> 02:48:01,720
>>THE PRACTICAL ANSWER

3761
02:48:01,720 --> 02:48:04,360
SEPTEMBER OF 2022 IS IMAGING.

3762
02:48:04,360 --> 02:48:07,160
MR. QUANTITATIVE MR. WE LIKE

3763
02:48:07,160 --> 02:48:09,640
THESE SERUM BIOMARKERS OR URINE

3764
02:48:09,640 --> 02:48:12,240
BIOMARKERS OR SYNOVIAL FLUID

3765
02:48:12,240 --> 02:48:14,160
BIOMARKERS. WE ARE NOT THERE BUT

3766
02:48:14,160 --> 02:48:16,640
WE USE IMAGING NOT PERFECT AND

3767
02:48:16,640 --> 02:48:21,960
HETEROGENEITY.  AS WE

3768
02:48:21,960 --> 02:48:23,200
CHARACTERIZE THE PHENOTYPE LEADS

3769
02:48:23,200 --> 02:48:25,200
TO POTENTIAL PRECISION MEDICINE

3770
02:48:25,200 --> 02:48:27,760
APPROACH. ONE SIZE DOES NOT FIT

3771
02:48:27,760 --> 02:48:30,840
ALL. PATIENT NEEDS -- THIS NEEDS

3772
02:48:30,840 --> 02:48:33,480
PRP, THIS ONE NEEDS TO BE SMALL

3773
02:48:33,480 --> 02:48:37,240
MOLECULE, THIS PATIENT WILL DO

3774
02:48:37,240 --> 02:48:40,120
(INAUDIBLE) IF YOU DO NOTHING.

3775
02:48:40,120 --> 02:48:43,120
>>THOSE PATIENTS EXIST.
TREAT

3776
02:48:43,120 --> 02:48:47,880
THE PATIENT NOT THE MRI.

3777
02:48:47,880 --> 02:48:50,200
>>SHOULD WE -- ANY OTHER

3778
02:48:50,200 --> 02:48:51,080
QUESTIONS, SHOULD WE MOVE ON?

3779
02:48:51,080 --> 02:48:52,520
>>I HAVE A QUESTION.

3780
02:48:52,520 --> 02:49:01,760
>>LARISS LARISSA. SHE HAS
HER  

3781
02:49:01,760 --> 02:49:04,800
>>KNEW FOR THE NICE
OVERVIEW OF

3782
02:49:04,800 --> 02:49:06,000
THE CHONDROCYTE IMPLANTATION

3783
02:49:06,000 --> 02:49:07,720
PRODUCTS. I WILL TAKE MY

3784
02:49:07,720 --> 02:49:10,520
REGULATORY HAT OFF AND PUT MY

3785
02:49:10,520 --> 02:49:11,600
SCIENTIFIC ON SO I HAVE A

3786
02:49:11,600 --> 02:49:13,800
QUESTION FOR YOU ABOUT YOUR

3787
02:49:13,800 --> 02:49:16,760
THOUGHTS ON WORKING WITH SOME OF

3788
02:49:16,760 --> 02:49:24,880
THESE PRODUCTS, HOW CAN WE

3789
02:49:24,880 --> 02:49:30,120
POSSIBILITY ACHIEVE MORE

3790
02:49:30,120 --> 02:49:31,640
FORMATION VERSUS CARTILAGE, NO

3791
02:49:31,640 --> 02:49:32,920
MATTER HOW WELL THEY PERFORM

3792
02:49:32,920 --> 02:49:37,720
SOMETIMES NOT WELL, IN VIVO

3793
02:49:37,720 --> 02:49:41,720
EVENTUALLY WAS YEARS, THE

3794
02:49:41,720 --> 02:49:43,200
FIBROCARTILAGE FORMATION WITH

3795
02:49:43,200 --> 02:49:45,440
THESE PRODUCTS SO ANY THOUGHTS

3796
02:49:45,440 --> 02:49:45,920
ON THIS?

3797
02:49:45,920 --> 02:49:49,000
>>I THINK ACTUALLY DANIEL
SARIS

3798
02:49:49,000 --> 02:49:52,000
WAS INVOLVED WITH THIS. THERE

3799
02:49:52,000 --> 02:49:54,400
WAS A EFFORT BY A COMPANY THAT

3800
02:49:54,400 --> 02:49:59,040
IS NO LONGER DOING TIGENICS

3801
02:49:59,040 --> 02:50:01,240
WHICH LOOKED AT HOW THE

3802
02:50:01,240 --> 02:50:03,880
PERFORMANCE OF THE CHONDROCYTE

3803
02:50:03,880 --> 02:50:04,960
WAS BEFORE IMPLANTATION. SO IN

3804
02:50:04,960 --> 02:50:07,280
OTHER WORDS WE KNOW THAT WE

3805
02:50:07,280 --> 02:50:09,760
EXPAND CHONDROCYTES FOR PERIOD

3806
02:50:09,760 --> 02:50:14,320
OF TIME IN CULTURE, THEY

3807
02:50:14,320 --> 02:50:17,160
DIFFERENTIATE. SO WHEN WE PUT

3808
02:50:17,160 --> 02:50:19,600
THEM BACK IN, EARLY ACI WITH THE

3809
02:50:19,600 --> 02:50:22,200
ADDITION OF THE HYPERPLASIA OF

3810
02:50:22,200 --> 02:50:29,320
THE PERIOUTSIDE YUM, HOW THE

3811
02:50:29,320 --> 02:50:29,880
CHONDROCYTES BEHIND IN THOSE

3812
02:50:29,880 --> 02:50:32,480
PRODUCTS IS IMPORTANT AND WAYS

3813
02:50:32,480 --> 02:50:35,440
TO ENSURE ADEQUATE MATURATION.

3814
02:50:35,440 --> 02:50:37,360
THE NOVA CARD HAS MADE THAT A

3815
02:50:37,360 --> 02:50:39,240
BETTER APPROACH TO THAT IN THE

3816
02:50:39,240 --> 02:50:42,000
SENSE THEY HAVE A MORE ROBUST

3817
02:50:42,000 --> 02:50:43,880
CARTILAGE FORMATION BECAUSE AS I

3818
02:50:43,880 --> 02:50:45,000
MENTION YOU HAVE GOOD CARTILAGE

3819
02:50:45,000 --> 02:50:48,720
IT WILL RESIST FIBROUS. BUT

3820
02:50:48,720 --> 02:50:52,720
FIBROUS INVASION. BUT THE REAL

3821
02:50:52,720 --> 02:50:56,400
PROBLEM I THINK IS THE SITE OF

3822
02:50:56,400 --> 02:50:58,320
ARCHITECTURE OF CARTILA CARTILAE

3823
02:50:58,320 --> 02:50:59,920
HAVE THAT UNIQUE ENGINEER -- IF

3824
02:50:59,920 --> 02:51:05,840
YOU WANT TO CALL IT DIVINE

3825
02:51:05,840 --> 02:51:07,440
ENGINEERING BUT THE ARCADE IT IS

3826
02:51:07,440 --> 02:51:10,440
WAY THE COLLAGEN FIBERS ARE

3827
02:51:10,440 --> 02:51:11,600
ORIENTED, HAS NOT BEEN

3828
02:51:11,600 --> 02:51:16,560
REPRODUCED BY ANYONE. WE MIGHT

3829
02:51:16,560 --> 02:51:20,760
AS WELL PUT IN A PLUG OF EAR

3830
02:51:20,760 --> 02:51:23,040
CARTILAGE OR RIB CARTILAGE

3831
02:51:23,040 --> 02:51:26,600
BECAUSE IT IS JUST -- IT HAS NO

3832
02:51:26,600 --> 02:51:27,520
STRUCTURAL INTEGRITY AS FAR AS

3833
02:51:27,520 --> 02:51:32,160
I'M CONCERNED, AS FAR AS THE

3834
02:51:32,160 --> 02:51:34,360
ORGANIZATION OF THE

3835
02:51:34,360 --> 02:51:35,680
CYTOARCHITECTURAL LEVEL. THAT IS

3836
02:51:35,680 --> 02:51:37,640
A KEY CHALLENGE FOR US. THAT

3837
02:51:37,640 --> 02:51:39,440
WOULD BE SOME OF MY COMMENTS ON

3838
02:51:39,440 --> 02:51:42,040
THAT. 

3839
02:51:42,040 --> 02:51:43,840
>>THANK YOU, THE REAL
ISSUE IS

3840
02:51:43,840 --> 02:51:46,640
DURABILITY OF THE EFFECT. TWO OR

3841
02:51:46,640 --> 02:51:52,560
THREE YEARS DOWN THE ROAD WE SEE

3842
02:51:52,560 --> 02:51:55,440
DATA, OTHER SURGERIES NEEDED OR

3843
02:51:55,440 --> 02:51:58,040
OTHER THINGS HAPPENING. SO

3844
02:51:58,040 --> 02:52:02,520
REALLY TRYING TO DO UP FRONT A

3845
02:52:02,520 --> 02:52:05,280
PRODUCT BETTER WITH EVENTUAL

3846
02:52:05,280 --> 02:52:06,520
HYALIN CARTILAGE FORMATION WOULD

3847
02:52:06,520 --> 02:52:14,040
BE A GOAL HERE.

3848
02:52:14,040 --> 02:52:18,160
>>WE CAN MOVE ON

3849
02:52:18,160 --> 02:52:20,040
>>PLEASURE TO ENTER DEUCE
MY

3850
02:52:20,040 --> 02:52:21,680
FRIEND AND COLLEAGUE DANIEL

3851
02:52:21,680 --> 02:52:23,760
SARIS, PAST PRESIDENT OF THE

3852
02:52:23,760 --> 02:52:25,720
ICRS, CURRENTLY ON THE

3853
02:52:25,720 --> 02:52:28,200
ORTHOPEEDIC STAFF MAYOR CLINIC

3854
02:52:28,200 --> 02:52:30,560
ROCHESTER WHERE HE FIRST

3855
02:52:30,560 --> 02:52:31,680
PROGENITOR, PROFESSOR

3856
02:52:31,680 --> 02:52:33,120
REGENERATIVE MEDICINE AT MAYO

3857
02:52:33,120 --> 02:52:36,920
CLINIC. HE TRAINED AT AMSTERDAM,

3858
02:52:36,920 --> 02:52:39,240
COMPLETED Ph.D. IN THE

3859
02:52:39,240 --> 02:52:41,480
NETHERLANDS, BIOLOGICAL JOINT

3860
02:52:41,480 --> 02:52:42,520
RECONSTRUCTION AND HE'S

3861
02:52:42,520 --> 02:52:44,480
DEPARTMENT OF ORTHOPEDICS FOR 17

3862
02:52:44,480 --> 02:52:46,640
YEARS, PART OF THE FOUNDING

3863
02:52:46,640 --> 02:52:51,080
MEMBER AND ORGANIZER FOR

3864
02:52:51,080 --> 02:52:54,440
REGENERATIVE MEDICINES IN

3865
02:52:54,440 --> 02:52:56,280
UTRECHT. HE ESTABLISHES JOINT

3866
02:52:56,280 --> 02:52:57,520
PRESERVATION APPROACHES IN

3867
02:52:57,520 --> 02:52:58,920
EUROPE AND THE USA AND TALK

3868
02:52:58,920 --> 02:53:00,600
ABOUT THE ROLE OF EXOSOMES AND

3869
02:53:00,600 --> 02:53:03,720
EXTRA CELLULAR VESICALES.

3870
02:53:03,720 --> 02:53:05,520
>>THANK YOU VERY MUCH,
SCOTT

3871
02:53:05,520 --> 02:53:07,080
FOR ORGANIZATION OF PUTTING THIS

3872
02:53:07,080 --> 02:53:08,600
TOGETHER. PROVIDING ME WITH

3873
02:53:08,600 --> 02:53:09,960
CHALLENGE OF READING UP DOING

3874
02:53:09,960 --> 02:53:11,240
SOME THINKING ON WHAT I FEEL

3875
02:53:11,240 --> 02:53:12,520
ABOUT THIS. WHAT THE SCIENCE

3876
02:53:12,520 --> 02:53:14,520
SAYS AND WHAT I FEEL COMFORTABLE

3877
02:53:14,520 --> 02:53:15,520
SHARING. THAT WAS AN INTERESTING

3878
02:53:15,520 --> 02:53:21,880
ONE. SO I WAS ASKED TO ADDRESS

3879
02:53:21,880 --> 02:53:25,240
THE ROLE IF ANY FOR USING EXTRA

3880
02:53:25,240 --> 02:53:27,520
CELLULAR VESICLES OR EXOSOMES

3881
02:53:27,520 --> 02:53:28,680
FOR TREATMENT OF OSTEOARTHRITIS.

3882
02:53:28,680 --> 02:53:30,400
FAIR TO SAY THERE IS A ROLE,

3883
02:53:30,400 --> 02:53:32,560
THERE ARE CONSIDERABLE

3884
02:53:32,560 --> 02:53:33,800
CHALLENGES AND I WOULD LOVE

3885
02:53:33,800 --> 02:53:35,520
DISCUSS WITH GROUP REALITIES

3886
02:53:35,520 --> 02:53:37,720
WHERE WE ARE NOW AND WHERE WE

3887
02:53:37,720 --> 02:53:45,720
ARE GOING TO BE. I KNOW TOLD US

3888
02:53:45,720 --> 02:53:47,520
PREPARATION WHICH IS METICULOUS

3889
02:53:47,520 --> 02:53:49,080
DON'T SAY THE SOLUTION IS MORE

3890
02:53:49,080 --> 02:53:51,000
MONEY AND I WILL STICK TO THAT.

3891
02:53:51,000 --> 02:53:52,240
NOT GOING TO SAY WE NEED MORE

3892
02:53:52,240 --> 02:53:54,080
MONEY. WE NEED MORE

3893
02:53:54,080 --> 02:53:55,840
UNDERSTANDING FIRST. BUT I DO --

3894
02:53:55,840 --> 02:53:59,080
I KNOW I'M PREACHING TO THE

3895
02:53:59,080 --> 02:54:03,200
CHOIR, I FEEL THAT WE AS WE DO

3896
02:54:03,200 --> 02:54:05,920
SO IN OUR SCIENCE AND GRANTS AND

3897
02:54:05,920 --> 02:54:06,800
PRESENTATIONS NEED TO BE WARE OF

3898
02:54:06,800 --> 02:54:08,480
THE FACT FOR THE UNITED STATES

3899
02:54:08,480 --> 02:54:10,040
NUMBERS ARE DAUNTING BECAUSE

3900
02:54:10,040 --> 02:54:16,160
NUMBER OF PEOPLE WITH

3901
02:54:16,160 --> 02:54:18,720
SYMPTOMATIC OA IS 11, 12% AT THE

3902
02:54:18,720 --> 02:54:20,600
MOMENT, EXPECTED TO DOUBLING IN

3903
02:54:20,600 --> 02:54:21,920
15 YEARS WHICH HAS ECONOMICAL

3904
02:54:21,920 --> 02:54:23,920
BURDEN. WE DID SOME MODELING FOR

3905
02:54:23,920 --> 02:54:27,680
ASIA, INCLUDING INDIA AND CHINA.

3906
02:54:27,680 --> 02:54:29,720
IF YOU LOOK AT THE VOLUME OF

3907
02:54:29,720 --> 02:54:30,680
PEOPLING THE EFFECTED BY THIS,

3908
02:54:30,680 --> 02:54:36,400
IT IS CONSIDERABLE. WITH

3909
02:54:36,400 --> 02:54:37,880
CONSIDERABLE ECONOMIC DRIVE TO

3910
02:54:37,880 --> 02:54:39,000
DO SO SO DON'T DISREGARD THE

3911
02:54:39,000 --> 02:54:41,320
FACT IT IS SEVERE DISEASE, WHO

3912
02:54:41,320 --> 02:54:43,520
CONSIDERED IT SEVERE DISEASE, UP

3913
02:54:43,520 --> 02:54:46,720
THERE WITH CANCER, PSYCHIATRIC

3914
02:54:46,720 --> 02:54:48,440
CHALLENGES AND CARDIOVASCULAR

3915
02:54:48,440 --> 02:54:50,080
AND WE SHOULD ZOOM IN FOR NEEDS

3916
02:54:50,080 --> 02:54:53,880
WE HAVE AS A FIELD.  THAT IS ALL

3917
02:54:53,880 --> 02:54:56,200
I NEED TO SAY ABOUT THAT PAR PA.

3918
02:54:56,200 --> 02:54:58,640
MONEY FOR US TO FIND NOT THROUGH

3919
02:54:58,640 --> 02:54:59,920
THIS PROGRAM AND NOT TODAY. IF

3920
02:54:59,920 --> 02:55:03,800
YOU LOOK AT THE LITERATURE ABOUT

3921
02:55:03,800 --> 02:55:05,240
EXTRA CELLULAR VESICALS WE DID

3922
02:55:05,240 --> 02:55:07,520
THIS WEEK, I NEED TO THANK MY

3923
02:55:07,520 --> 02:55:09,840
FRIEND AND COLLEAGUE FOR HIS

3924
02:55:09,840 --> 02:55:10,840
WORK PREPARING THIS. IT IS CLEAR

3925
02:55:10,840 --> 02:55:13,920
IT IS RAPIDLY DEVELOPING YOUNG

3926
02:55:13,920 --> 02:55:15,760
FIELD WITH INCREASING NUMBER OF

3927
02:55:15,760 --> 02:55:17,280
PUBLICATIONS ON EXOSOMES AND

3928
02:55:17,280 --> 02:55:19,160
EXTRA CELLULAR VESICALES BUT

3929
02:55:19,160 --> 02:55:20,760
ALSO STILL VERY EARLY DAYS. IF

3930
02:55:20,760 --> 02:55:24,640
YOU COMPARE THIS TO ANY TOPICS

3931
02:55:24,640 --> 02:55:26,200
DISCUSSED TODAY, THERE'S WAY

3932
02:55:26,200 --> 02:55:27,960
LESS PUBLICATIONS. YOU CAN SEE

3933
02:55:27,960 --> 02:55:30,760
THERE SEEMS TO BE A SHIFT OF

3934
02:55:30,760 --> 02:55:34,360
PUBLICATIONS ON MSCs. TO MAYBE

3935
02:55:34,360 --> 02:55:35,960
NOW SHIFT ON PEOPLE SAYING YOUR

3936
02:55:35,960 --> 02:55:40,040
LAB AND YOU DO WORK ON MSC, OUR

3937
02:55:40,040 --> 02:55:42,680
MOVE TO FOCUS ON EXOSOMES

3938
02:55:42,680 --> 02:55:43,880
BECAUSE MAYBE MORE COMPLEX TO

3939
02:55:43,880 --> 02:55:45,760
USE CELLS AND MAYBE USE OFF THE

3940
02:55:45,760 --> 02:55:48,000
SHELF TECHNOLOGY WHERE WE USE

3941
02:55:48,000 --> 02:55:50,080
EXOSOMES AS END PRODUCT OF MSC

3942
02:55:50,080 --> 02:55:53,080
OR END PRODUCT OF SOME OF THESE

3943
02:55:53,080 --> 02:55:54,400
CELLULAR COMMUNICATION METHODS

3944
02:55:54,400 --> 02:55:56,840
TO INFLUENCE OSTEOARTHRITIS OR

3945
02:55:56,840 --> 02:55:58,920
INFLUENCE OTHER DISEASES. THIS

3946
02:55:58,920 --> 02:56:00,920
SLIDE SHOWS THE RAPID INCREASE

3947
02:56:00,920 --> 02:56:04,720
IN THE FIELD BUT ALSO STILL

3948
02:56:04,720 --> 02:56:06,400
LIMITED KNOW HOW. WHICH IS

3949
02:56:06,400 --> 02:56:07,480
INTERESTING BECAUSE THE FIRST

3950
02:56:07,480 --> 02:56:08,920
DESCRIPTIONS OF WHAT I THINK WAS

3951
02:56:08,920 --> 02:56:11,560
MEANT TO BE THE DESCRIPTION OF

3952
02:56:11,560 --> 02:56:13,880
EXOSOMES WAS PLATELET DUST, THAT

3953
02:56:13,880 --> 02:56:15,800
IS WHAT IT SAYS IN THE PAPER

3954
02:56:15,800 --> 02:56:18,480
THAN 1960s. AND WE ARE TRYING

3955
02:56:18,480 --> 02:56:20,120
TO DEFINE THIS IS SIMILAR TO

3956
02:56:20,120 --> 02:56:22,040
DISCUSSION THAT DR. RODEO AND WE

3957
02:56:22,040 --> 02:56:23,760
ALL HAD EARLIER ON IN OUR

3958
02:56:23,760 --> 02:56:25,520
UNDERSTANDING OF MSC. WE ARE

3959
02:56:25,520 --> 02:56:28,040
STILL TRYING TO DEFINE WHAT

3960
02:56:28,040 --> 02:56:28,960
EXOSOMES AND WHICH DIFFERENT

3961
02:56:28,960 --> 02:56:36,440
EXOSOMES ARE THERE.  THEY PLAY A

3962
02:56:36,440 --> 02:56:38,320
ROLE IN INTRACELLULAR

3963
02:56:38,320 --> 02:56:39,480
COMMUNICATION. THEY THEREFORE

3964
02:56:39,480 --> 02:56:41,040
PLAY ROLE IN CELLULAR RESPONSE,

3965
02:56:41,040 --> 02:56:43,480
TISSUE RESPONSE TO TRAUMA,

3966
02:56:43,480 --> 02:56:45,040
DISEASE, MALIGNANCY AND ALSO

3967
02:56:45,040 --> 02:56:48,800
RESTORE HOMEOSTASIS.  

3968
02:56:48,800 --> 02:56:50,240
INTERESTINGLY ENOUGH ONGOING

3969
02:56:50,240 --> 02:56:52,960
EVIDENCE THAT NOT ONLY DO

3970
02:56:52,960 --> 02:56:55,040
EXOSOMES PLAY ROLE IN CELL

3971
02:56:55,040 --> 02:56:59,000
TISSUE OR TISSUE CELL

3972
02:56:59,000 --> 02:57:00,560
COMMUNICATION, THEY CHANGE WHAT

3973
02:57:00,560 --> 02:57:02,480
IS IN THE EXOSOME OR WHAT THE

3974
02:57:02,480 --> 02:57:03,800
EXOSOME DOES WITHIN THE TISSUE

3975
02:57:03,800 --> 02:57:04,600
LISTENING TO THE ENVIRONMENT

3976
02:57:04,600 --> 02:57:07,280
WHICH THEY ARE BEING SECRETED.

3977
02:57:07,280 --> 02:57:10,400
THIS MEANS IT IS A SMART

3978
02:57:10,400 --> 02:57:12,360
FEEDBACK SYSTEM, WHICH FOR ME IS

3979
02:57:12,360 --> 02:57:15,120
SUPER INTERESTING BUT IT CREATES

3980
02:57:15,120 --> 02:57:17,320
A FUNDAMENTAL CHALLENGE IN THE

3981
02:57:17,320 --> 02:57:19,000
CONCEPT OF USING THEM OFF THE

3982
02:57:19,000 --> 02:57:23,920
SHELF INSTEAD OF MSCs OR OTHER

3983
02:57:23,920 --> 02:57:25,720
CELL SOURCES. MORE DYNAMIC THAN

3984
02:57:25,720 --> 02:57:27,600
THEY ARE CURRENTLY BEING THOUGHT

3985
02:57:27,600 --> 02:57:29,280
OF THAN THE WAY I UNDERSTAND THE

3986
02:57:29,280 --> 02:57:32,040
SCIENCE BEING DISCUSSED. I STILL

3987
02:57:32,040 --> 02:57:34,440
THINK THE FIELD IS YOUNG, EARLY

3988
02:57:34,440 --> 02:57:36,560
DAYS, THERE ARE COUPLE OF EXPERT

3989
02:57:36,560 --> 02:57:38,120
CENTERS HERE IN THE UNITED

3990
02:57:38,120 --> 02:57:39,200
STATES, WHERE I THINK WE ARE

3991
02:57:39,200 --> 02:57:40,680
STILL TRYING TO FIGURE OUT WHAT

3992
02:57:40,680 --> 02:57:43,840
IS EXOSOME AND WHAT ARE OTHER

3993
02:57:43,840 --> 02:57:44,840
CELL SECRETORY MECHANISMS

3994
02:57:44,840 --> 02:57:47,480
AVAILABLE THAT ARE SIMILAR AND

3995
02:57:47,480 --> 02:57:48,400
HOW DO THEY KNIFER FROM EACH

3996
02:57:48,400 --> 02:57:50,080
OTHER. AT THE MOMENT WE ARE

3997
02:57:50,080 --> 02:57:53,080
STILL IN A PHASE SEPARATION OR

3998
02:57:53,080 --> 02:57:55,160
COLLECTION OF EXOSOMES AND

3999
02:57:55,160 --> 02:57:57,160
FUNCTIONAL DESCRIPTION IS BEING

4000
02:57:57,160 --> 02:58:00,160
DONE BY THINGS WE CAN SEE AND

4001
02:58:00,160 --> 02:58:03,200
MEASURE IN ELECTRON MICROSCOPY,

4002
02:58:03,200 --> 02:58:09,240
SIZE DETERMINATION, EARLY

4003
02:58:09,240 --> 02:58:10,960
STUDIES THAT FOCUS ON EXOSOME

4004
02:58:10,960 --> 02:58:15,520
FUNCTION. IT IS ONE OF THE

4005
02:58:15,520 --> 02:58:19,040
CHALLENGES IN THE THERAPEUTIC

4006
02:58:19,040 --> 02:58:20,720
APPLICATION OF EXOSOMES, TRYING

4007
02:58:20,720 --> 02:58:23,080
TO FIGURE HOW TO GET IT FROM THE

4008
02:58:23,080 --> 02:58:26,280
FLUID OR TISSUE THEY ARE

4009
02:58:26,280 --> 02:58:28,480
FUNCTIONING IN. THE WAY I READ

4010
02:58:28,480 --> 02:58:31,120
LITERATURE, THERE ARE FOUR WAYS

4011
02:58:31,120 --> 02:58:34,280
AT THE MOMENT SIMPLE RELIABLE IS

4012
02:58:34,280 --> 02:58:37,160
ULTRA CENTRIFICATION, HAS

4013
02:58:37,160 --> 02:58:38,400
ADVANTAGES BUT DOWN SIDES AS

4014
02:58:38,400 --> 02:58:39,320
WELL BECAUSE ON INDIVIDUAL

4015
02:58:39,320 --> 02:58:40,640
PATIENT TO PATIENT BASIS IT WILL

4016
02:58:40,640 --> 02:58:42,960
BE DIFFICULT TO MAKE THIS

4017
02:58:42,960 --> 02:58:45,280
APPLICABLE. AS YOU TRY TO DO FOR

4018
02:58:45,280 --> 02:58:47,680
LARGER VOLUMES AND COHORT THERE

4019
02:58:47,680 --> 02:58:49,480
WILL BE LIMITATIONS ON

4020
02:58:49,480 --> 02:58:50,560
FLEXIBILITY AND EFFECTIVENESS OF

4021
02:58:50,560 --> 02:58:54,600
CHOICE.  THERE ARE MORE SPECIFIC

4022
02:58:54,600 --> 02:58:58,200
METHODS SUCH AS SIZE TECHNIQUES

4023
02:58:58,200 --> 02:59:04,040
WITH ULTRA FILTRATION AND

4024
02:59:04,040 --> 02:59:07,920
CHROMATOGRAPHY AND PRETTY

4025
02:59:07,920 --> 02:59:10,440
DIFFICULT HOW TO UP SCALE THOSE.

4026
02:59:10,440 --> 02:59:13,000
MAYBE EXOSOME PRECIPITATION

4027
02:59:13,000 --> 02:59:18,960
FILTERING IN RUDIMENTARY WAY UP

4028
02:59:18,960 --> 02:59:21,280
SCALE, BUT ONCE WE START

4029
02:59:21,280 --> 02:59:22,760
UNDERSTANDING SPECIFIC EXOSOME

4030
02:59:22,760 --> 02:59:25,720
FUNCTIONS THEREFORE LIKELY THAT

4031
02:59:25,720 --> 02:59:27,840
IMMUNE AFFINITY CAPTURE BASED

4032
02:59:27,840 --> 02:59:29,240
TECHNIQUES WOULD BE LIKELY TO

4033
02:59:29,240 --> 02:59:33,320
ADDRESS CERTAIN EXOSOMES TO BE

4034
02:59:33,320 --> 02:59:34,880
EXTRACTED AS MAYBE TRYING

4035
02:59:34,880 --> 02:59:37,120
SECRETE FROM MSC CONTROLLED

4036
02:59:37,120 --> 02:59:39,200
ENVIRONMENT OR EVEN SYNOVIAL

4037
02:59:39,200 --> 02:59:40,880
FLUID CONTROLLED ENVIRONMENT

4038
02:59:40,880 --> 02:59:44,440
THAT PREDICTABLY CREATE EXOSOME

4039
02:59:44,440 --> 02:59:46,960
POPULATION YOU WANT TO FIND MANY

4040
02:59:46,960 --> 02:59:49,560
A MORE INDUSTRIAL ENVIRONMENT.

4041
02:59:49,560 --> 02:59:52,840
SEEMS TO BE FAR AHEAD OF THE

4042
02:59:52,840 --> 02:59:54,520
FIELD BUT LEARNED IF YOU DON'T

4043
02:59:54,520 --> 02:59:58,360
KNOW HOW TO UPSCALE AND MAKE

4044
02:59:58,360 --> 02:59:59,360
APPLICABLE YOU HAVE TO WONDER

4045
02:59:59,360 --> 03:00:01,040
WHAT THE FUNDAMENTAL RESEARCH

4046
03:00:01,040 --> 03:00:02,400
NEEDS TO BE STEER US TOWARDS,

4047
03:00:02,400 --> 03:00:03,960
THIS IS STILL VERY MUCH WHERE

4048
03:00:03,960 --> 03:00:06,520
THE EXOSOME FIELD IS AT.  SO

4049
03:00:06,520 --> 03:00:09,400
WHAT IS THERE AND HOW IS THIS

4050
03:00:09,400 --> 03:00:11,280
GOING TO BE APPLICABLE TO OA

4051
03:00:11,280 --> 03:00:12,840
TREATMENT, WAS THE QUESTION WE

4052
03:00:12,840 --> 03:00:14,600
TRIED TO READ MORE. IT IS CLEAR

4053
03:00:14,600 --> 03:00:18,040
AS I REFERRED TO BEFORE, MS A

4054
03:00:18,040 --> 03:00:19,360
FIELD UNDERSTANDING THE ROLE OF

4055
03:00:19,360 --> 03:00:23,360
MSCs IN IMMUNE MODULATORY BUT

4056
03:00:23,360 --> 03:00:26,840
ALSO IN SECESSION OF BIOACTIVE

4057
03:00:26,840 --> 03:00:28,800
FACTORS, THAT IS VERY MUCH

4058
03:00:28,800 --> 03:00:30,840
FOCUSED ON THE ROLES OF EXOSOMES

4059
03:00:30,840 --> 03:00:33,680
AS INTRACELLULAR MECHANISM. IT

4060
03:00:33,680 --> 03:00:36,040
IS CLEAR AS WE HEARD TODAY AND

4061
03:00:36,040 --> 03:00:37,360
HAVE SEEN BEFORE, THERE IS AN

4062
03:00:37,360 --> 03:00:41,160
EFFECT OF MSCs ON OSTEO

4063
03:00:41,160 --> 03:00:42,480
ARTHRITIC JOINTS ON

4064
03:00:42,480 --> 03:00:45,200
DEGENERATION, SYNOVIAL PROCESS,

4065
03:00:45,200 --> 03:00:46,120
WE ARE STILL IN THE PROCESS OF

4066
03:00:46,120 --> 03:00:46,880
GAINING BETTER UNDERSTANDING OF

4067
03:00:46,880 --> 03:00:50,680
THAT. BUT IT IS CLEAR EXOSOMES

4068
03:00:50,680 --> 03:00:53,440
PLAY A ROLE IN THAT. THEREFORE

4069
03:00:53,440 --> 03:00:54,560
WE SEE THESE JUNE YUP SLOPE IN

4070
03:00:54,560 --> 03:00:56,680
PUBLICATION ON EXOSOMES SINCE WE

4071
03:00:56,680 --> 03:00:57,720
NOW MORE ACCEPT AND UNDERSTAND

4072
03:00:57,720 --> 03:01:01,040
THAT THE PARACRINE FUNCTION OF

4073
03:01:01,040 --> 03:01:03,120
MSC MIGHT BE MORE IMPORTANT THAN

4074
03:01:03,120 --> 03:01:05,360
TISSUE DIFFERENTIATION AND

4075
03:01:05,360 --> 03:01:07,800
REGENERATION FROM MSC PER SE.

4076
03:01:07,800 --> 03:01:08,920
THEREFORE MAKES SENSE THAT YES

4077
03:01:08,920 --> 03:01:12,560
THERE IS A HYPOTHESIS THAT'S

4078
03:01:12,560 --> 03:01:15,000
STRONG ENOUGH INITIAL IN VITRO

4079
03:01:15,000 --> 03:01:17,640
EVIDENCE THAT EXOSOMES DO PLAY A

4080
03:01:17,640 --> 03:01:19,320
ROLE IN THE POSSIBILITIES AND IN

4081
03:01:19,320 --> 03:01:21,040
THE PORTFOLIO OF MAYBE DOING

4082
03:01:21,040 --> 03:01:22,920
SOMETHING IN EARLY PHASE

4083
03:01:22,920 --> 03:01:24,960
INTERVENTION OF THIS CASCADE OF

4084
03:01:24,960 --> 03:01:29,200
THINGS THAT EVENTUALLY IT WAS

4085
03:01:29,200 --> 03:01:31,160
OSTEOARTHRITIS. THERE ARE FEW

4086
03:01:31,160 --> 03:01:33,000
REVIEW PAPERS THAT STEER US

4087
03:01:33,000 --> 03:01:35,440
TOWARDS BETTER UNDERSTANDING.

4088
03:01:35,440 --> 03:01:38,200
THERE ARE SOME PAPERS THAT SHOW

4089
03:01:38,200 --> 03:01:41,960
MECHANISMS OF ACTION AND MOST OF

4090
03:01:41,960 --> 03:01:44,400
THEM ARE ARE NOW MSC DERIVED

4091
03:01:44,400 --> 03:01:46,720
EXOSOMES AND HOW DO THEY PROTECT

4092
03:01:46,720 --> 03:01:51,000
CARTILAGE OR HOW DO THEY PROTECT

4093
03:01:51,000 --> 03:01:52,600
BONE FEE FORMATION OR MODULATE

4094
03:01:52,600 --> 03:01:55,520
SYNOVIAL INFLAMMATORY PROCESSES 

4095
03:01:55,520 --> 03:01:56,960
THEY ARE SUFFICIENT EVIDENCEED

4096
03:01:56,960 --> 03:01:59,160
FROM EXOSOME BASE RESEARCH

4097
03:01:59,160 --> 03:02:02,000
MAINLY FROM MSC DERIVED EXOSOME

4098
03:02:02,000 --> 03:02:05,360
DERIVED MSC THAT THERE IS A

4099
03:02:05,360 --> 03:02:08,400
CHONDRAL PROTECTIVE EFFECT THERE

4100
03:02:08,400 --> 03:02:09,080
IS CHONDRAL SUPPORTIVE EFFECT

4101
03:02:09,080 --> 03:02:15,040
THROUGH BOTH CHONDROCYTE

4102
03:02:15,040 --> 03:02:17,040
APOPTOSIS AND MACROPHAGE

4103
03:02:17,040 --> 03:02:20,400
ACTIVATION. WHICH IS THE

4104
03:02:20,400 --> 03:02:22,480
DISCUSSION DR. LATTERMANN AND

4105
03:02:22,480 --> 03:02:24,480
ROBEY HAD BEFORE. THE PAPERS IN

4106
03:02:24,480 --> 03:02:26,040
MY UNDERSTANDING, SAY THAT THERE

4107
03:02:26,040 --> 03:02:28,480
IS STILL A GREAT HETEROGENEITY,

4108
03:02:28,480 --> 03:02:30,960
NOT ONLY IN THE CELL LINES

4109
03:02:30,960 --> 03:02:33,160
LOOKED AT TO STUDY EXOSOMES BUT

4110
03:02:33,160 --> 03:02:34,800
ALSO IN THE PREPARATION OF THE

4111
03:02:34,800 --> 03:02:37,240
SECRETOMES AND PANEL MODELS IN

4112
03:02:37,240 --> 03:02:39,800
VITRO MODELS, AND UNDERSTANDING

4113
03:02:39,800 --> 03:02:42,440
HOW TO USE SECRETOMES OF

4114
03:02:42,440 --> 03:02:43,880
RESOLUTION OF INFLAMMATION AND

4115
03:02:43,880 --> 03:02:45,720
CARTILAGE REGENERATION, WE TOOK

4116
03:02:45,720 --> 03:02:48,280
A LITTLE BIT OF PEAK IN ROLE OF

4117
03:02:48,280 --> 03:02:51,040
EXOSOMES IN OTHER FIELDSES I GET

4118
03:02:51,040 --> 03:02:52,800
THE SENSE ONCOLOGY FIELD IS

4119
03:02:52,800 --> 03:02:53,960
FURTHER AHEAD IN UNDERSTANDING

4120
03:02:53,960 --> 03:02:58,520
AND APPLICATION IN SOME OF THE

4121
03:02:58,520 --> 03:03:00,560
MALIGNANCIES. CARDIOVASCULAR

4122
03:03:00,560 --> 03:03:02,360
FIELD? SIMILAR PHASE AS WE ARE

4123
03:03:02,360 --> 03:03:06,680
IN NOW.  WHEN WE DID SEARCH FOR

4124
03:03:06,680 --> 03:03:08,160
CLINICAL TRIALS THERE ARE MORE

4125
03:03:08,160 --> 03:03:10,040
THAN 30 REGISTERED CLINICAL

4126
03:03:10,040 --> 03:03:13,240
TRIALS ON CLINI CLINICALTRIALS.V

4127
03:03:13,240 --> 03:03:14,960
THAT CIRCLE EXOSOME APPLICATION

4128
03:03:14,960 --> 03:03:17,640
BUT TWO-THIRDS ARE DIAGNOSTIC

4129
03:03:17,640 --> 03:03:20,440
PURPOSE, THERAPEUTIC PURPOSES

4130
03:03:20,440 --> 03:03:23,760
AND ALL BY FIVE OR SIX IN THE

4131
03:03:23,760 --> 03:03:25,000
ONCOLOGY FIELD. NONE AS FAR AS I

4132
03:03:25,000 --> 03:03:27,120
WAS ABLE TO FIND IN OUR SEARCH

4133
03:03:27,120 --> 03:03:30,760
TWO WEEKS AGO ARE IN THE

4134
03:03:30,760 --> 03:03:33,920
OSTEOARTHRITIS OR REGENERATION

4135
03:03:33,920 --> 03:03:35,360
CARTILAGE FIELD. I FEEL THE

4136
03:03:35,360 --> 03:03:36,920
BASIC SCIENCE SHOWS IN WHATEVER

4137
03:03:36,920 --> 03:03:39,840
ANIMAL MODEL YOU CHOOSE, THERE

4138
03:03:39,840 --> 03:03:41,960
IS SUFFICIENT EVIDENCE MSC BASED

4139
03:03:41,960 --> 03:03:45,200
EXOSOMES PLAY A ROLE IN SOME WAY

4140
03:03:45,200 --> 03:03:47,440
SHAPE OR FORM INFLUENCING

4141
03:03:47,440 --> 03:03:48,760
BENEFICIALLY ROLE OF CARTILAGE

4142
03:03:48,760 --> 03:03:50,840
REPAIR AND OUTCOME OF CARTILAGE

4143
03:03:50,840 --> 03:03:52,400
REPAIR THERE, IS A SOLID REASON

4144
03:03:52,400 --> 03:03:54,520
TO STUDY THIS. SO THEREFORE THE

4145
03:03:54,520 --> 03:03:58,160
CHARGE FOR TODAY'S EXPLORATION

4146
03:03:58,160 --> 03:04:00,600
WAS USEFUL. THERE ALSO SEEMED

4147
03:04:00,600 --> 03:04:01,840
SUFFICIENT EVIDENCE THAT

4148
03:04:01,840 --> 03:04:05,800
SYMPTOMATIC RELIEF FROM

4149
03:04:05,800 --> 03:04:07,720
OSTEOARTHRITIS COMPLAINTS

4150
03:04:07,720 --> 03:04:11,160
MEASURED BUT SYNOVIAL FLUID OR

4151
03:04:11,160 --> 03:04:12,160
THICKENING OR CHANGES CAN BE

4152
03:04:12,160 --> 03:04:15,360
MODIFIED BY THE APPLICATION OF

4153
03:04:15,360 --> 03:04:17,480
EXOSOMES, WE ARE THINKING DOSING

4154
03:04:17,480 --> 03:04:21,000
AND CLIMBING, THINKING

4155
03:04:21,000 --> 03:04:24,240
INTERACTIONS WITH THE GOAL

4156
03:04:24,240 --> 03:04:26,200
THERAPEUTIC TISSUES SO THAT

4157
03:04:26,200 --> 03:04:27,240
NEEDS TO BE SOLVED.  THERE ARE

4158
03:04:27,240 --> 03:04:29,040
MORE CHALLENGES AT THE MOMENT

4159
03:04:29,040 --> 03:04:31,960
THAN REAL SOLUTIONS AND TO ME

4160
03:04:31,960 --> 03:04:33,600
THERE IS NOT A CLEAR PATH

4161
03:04:33,600 --> 03:04:36,080
FORWARD YET. IT IS DIFFICULT TO

4162
03:04:36,080 --> 03:04:38,320
UNDERSTAND HOW WE HARVEST THEM,

4163
03:04:38,320 --> 03:04:40,680
DIFFICULT HOW TO DELIVER THEM.  

4164
03:04:40,680 --> 03:04:44,440
THERE ARE SOME BUY LOGICAL

4165
03:04:44,440 --> 03:04:46,240
CHALLENGES IN THE -- BIOLOGICAL

4166
03:04:46,240 --> 03:04:47,800
CHALLENGES IN THE INTERARTICULAR

4167
03:04:47,800 --> 03:04:49,280
ENVIRONMENT WHICH IS SIMPLER TO

4168
03:04:49,280 --> 03:04:51,160
SOLVE IF WE GO FOR ORGAN

4169
03:04:51,160 --> 03:04:54,040
SOLUTIONS OR INTRAVASCULAR

4170
03:04:54,040 --> 03:04:55,400
SOLUTIONS. IT IS DIFFICULT TO

4171
03:04:55,400 --> 03:04:56,880
UNDERSTAND WHAT WOULD BE THE

4172
03:04:56,880 --> 03:04:59,440
IDEAL SOURCE FOR MSC TO ISOLATE

4173
03:04:59,440 --> 03:05:01,680
EXOSOME FROM AND IF YOU WANT TO

4174
03:05:01,680 --> 03:05:03,360
UPSCALE, HOW TO COLLECT EXOSOMES

4175
03:05:03,360 --> 03:05:05,480
IN AN EFFICIENT MANNER FROM MSC

4176
03:05:05,480 --> 03:05:07,560
POPULATION.  WOULD BE A

4177
03:05:07,560 --> 03:05:08,600
DIFFERENT CHALLENGE. BUT I DON'T

4178
03:05:08,600 --> 03:05:11,000
THINK WE NEED TO ADDRESS THAT

4179
03:05:11,000 --> 03:05:12,520
YET.  WE ARE IN THE PHASE TO

4180
03:05:12,520 --> 03:05:14,760
LOOK AT MECHANISTIC EXPLORATION

4181
03:05:14,760 --> 03:05:16,440
AND UNDERSTANDING, THE ROOT OF

4182
03:05:16,440 --> 03:05:19,760
DELIVERY AND DOSAGE. FREQUENCY

4183
03:05:19,760 --> 03:05:21,880
PATIENT SELECTION COMES LAST. 

4184
03:05:21,880 --> 03:05:25,400
BUT THERE CLEARLY IS A EXCITING

4185
03:05:25,400 --> 03:05:27,120
OPPORTUNITY TO USE EXOSOMES FOR

4186
03:05:27,120 --> 03:05:29,600
TREATMENT OF OSTEOARTHRITIS. I

4187
03:05:29,600 --> 03:05:32,000
WOULD SAY THAT BUNDLING OF

4188
03:05:32,000 --> 03:05:33,360
FORCES FOCUS RESEARCH PROJECTS

4189
03:05:33,360 --> 03:05:39,000
AND PROTOCOLS AND PROBABLY CON

4190
03:05:39,000 --> 03:05:40,160
SOURCE IS IMPORTANT AND MAYBE

4191
03:05:40,160 --> 03:05:42,160
THIS GROUP CAN PLAY A ROLE IN

4192
03:05:42,160 --> 03:05:43,640
SOME WAY SHAPE OR FORM. I THINK

4193
03:05:43,640 --> 03:05:44,960
WHAT IS IMPORTANT AND MENTIONED

4194
03:05:44,960 --> 03:05:47,280
BY DR. RODEO, STANDARDIZATION OF

4195
03:05:47,280 --> 03:05:48,600
PROTOCOLS AND DESCRIPTION OF

4196
03:05:48,600 --> 03:05:51,200
WHAT IS MY EXOSOME I'M WORKING

4197
03:05:51,200 --> 03:05:53,400
ON HOW DID I GET IT, HOW DO

4198
03:05:53,400 --> 03:05:55,520
OTHERS USE IT REPRODUCIBLY IN

4199
03:05:55,520 --> 03:05:57,200
THE SAME WAY.  THOSE ARE NEEDED

4200
03:05:57,200 --> 03:05:59,640
BEFORE WE CAN START THINKING

4201
03:05:59,640 --> 03:06:00,960
ABOUT CLINICAL TRIALS IN

4202
03:06:00,960 --> 03:06:02,280
OSTEOARTHRITIS.  I FEEL THE

4203
03:06:02,280 --> 03:06:03,880
LIBERTY OF SCIENTIFIC

4204
03:06:03,880 --> 03:06:05,440
EXPLORATION IS PROBABLY A LITTLE

4205
03:06:05,440 --> 03:06:07,440
BIT BIGGER IN ONCOLOGY FOR

4206
03:06:07,440 --> 03:06:09,760
OBVIOUS REASONS. I THINK THERE

4207
03:06:09,760 --> 03:06:13,480
IS EVEN A POSSIBILITY OF

4208
03:06:13,480 --> 03:06:15,800
ENGINEERING EXTRA CELLULAR

4209
03:06:15,800 --> 03:06:17,400
VESICALES AND EXOSOMES WHICH IS

4210
03:06:17,400 --> 03:06:18,880
MORE CONTROLLABLE. THAT IS NOT

4211
03:06:18,880 --> 03:06:21,400
REALISTIC FOR CELLS, MIGHT BE

4212
03:06:21,400 --> 03:06:22,440
POSSIBLE TO ENGINEER FULL

4213
03:06:22,440 --> 03:06:25,680
EXOSOME IN A WAY THERAPEUTIC

4214
03:06:25,680 --> 03:06:26,880
OPTION DIFFERENT THAN APPLYING

4215
03:06:26,880 --> 03:06:29,680
SMALL MOLECULES. THERE ARE

4216
03:06:29,680 --> 03:06:32,000
THOUGHTS USING MSC EXOSOMES FROM

4217
03:06:32,000 --> 03:06:34,760
YOUNGER DONORS TO BE STORED IN

4218
03:06:34,760 --> 03:06:36,520
THEIR LIFE LATER ON WHICH IS

4219
03:06:36,520 --> 03:06:40,080
SOMETIMES ALLEVIATE CHALLENGES

4220
03:06:40,080 --> 03:06:43,560
THAT WE KNOW. USED AS A VESICLE

4221
03:06:43,560 --> 03:06:46,680
FOR DRUG DELIVERY. THAT IS WHERE

4222
03:06:46,680 --> 03:06:48,360
WE STAND WITH OUR UNDERSTANDING

4223
03:06:48,360 --> 03:06:49,720
AND I FEEL CONFIDENT AND

4224
03:06:49,720 --> 03:06:52,120
CHALLENGED ENOUGH TO SAY THAT

4225
03:06:52,120 --> 03:06:53,640
PRE-CLINICAL EVIDENCE SUGGESTS

4226
03:06:53,640 --> 03:07:01,840
THAT MSC DERIVED EXOSOMES JOINT

4227
03:07:01,840 --> 03:07:02,960
HOMEOSTASIS AND MAY PREVENT

4228
03:07:02,960 --> 03:07:04,400
OSTEOARTHRITIS IN ANIMAL MODELS

4229
03:07:04,400 --> 03:07:06,000
THERE'S ANTI-INFLAMMATORY

4230
03:07:06,000 --> 03:07:06,760
EFFECTS IN PATIENT CARE THAT

4231
03:07:06,760 --> 03:07:08,520
SHOULD BE TRIED WHEN WE KNOW HOW

4232
03:07:08,520 --> 03:07:12,840
TO DO SO SAFELY. SIGNALING OF

4233
03:07:12,840 --> 03:07:14,080
EXOSOME CHANGES AS THEY ARE

4234
03:07:14,080 --> 03:07:16,480
ENVIRONMENTS THAT CHANGE. I

4235
03:07:16,480 --> 03:07:19,600
THINK AS I SAID BEFORE THAT IS A

4236
03:07:19,600 --> 03:07:20,600
FUNDAMENTAL CHANGE TO OFF THE

4237
03:07:20,600 --> 03:07:22,080
SHELF USE BECAUSE WE MAY NOT BE

4238
03:07:22,080 --> 03:07:23,280
SMART ENOUGH TO DESIGN THE

4239
03:07:23,280 --> 03:07:25,280
EXOSOME THAT NEEDS TO BE USED

4240
03:07:25,280 --> 03:07:26,600
FOR CHANGING ENVIRONMENT THAT

4241
03:07:26,600 --> 03:07:28,360
THE PATIENT PRESENTS US WITH. SO

4242
03:07:28,360 --> 03:07:30,560
I THINK THAT FOR NOW WE SHOULD

4243
03:07:30,560 --> 03:07:33,560
TRY TO FOCUS AND CONCENTRATE THE

4244
03:07:33,560 --> 03:07:35,200
RESEARCH AND CREATE ROBUST

4245
03:07:35,200 --> 03:07:36,960
FOUNDATION OF UNDERSTANDING

4246
03:07:36,960 --> 03:07:39,160
BEFORE WE END UP IN APPROACHES

4247
03:07:39,160 --> 03:07:42,320
WE HAVE SEEN WITH THE OTHER

4248
03:07:42,320 --> 03:07:44,800
TECHNOLOGIES. THAT IS ALL I HAVE

4249
03:07:44,800 --> 03:07:46,440
FOR YOU IN THIS BUT I THINK IT

4250
03:07:46,440 --> 03:07:49,000
IS EARLY BUT EXCITING FIELD.  

4251
03:07:49,000 --> 03:07:50,280
THANK YOU VERY MUCH FOR THE

4252
03:07:50,280 --> 03:07:53,640
CHALLENGE.

4253
03:07:53,640 --> 03:07:55,800
>>THANK YOU, DANIEL.
GREAT

4254
03:07:55,800 --> 03:07:57,120
SUMMARY, IT NEEDS TO FURTHER

4255
03:07:57,120 --> 03:08:00,640
WORK. LIKE EVERYTHING ELSE,

4256
03:08:00,640 --> 03:08:02,280
CHARACTERIZATION OF THESE

4257
03:08:02,280 --> 03:08:03,320
PREPARATIONS IS SO CRITICAL.

4258
03:08:03,320 --> 03:08:06,000
>>AGREE. 

4259
03:08:06,000 --> 03:08:08,400
>>NICE TALK, DANIEL. DO
YOU

4260
03:08:08,400 --> 03:08:15,640
HAVE SOME SUGGESTIONS FOR HOW TO

4261
03:08:15,640 --> 03:08:17,360
CHARACTERIZE EXOSOME?

4262
03:08:17,360 --> 03:08:22,000
>>NO, I DON'T. THAT IS
NOT AN

4263
03:08:22,000 --> 03:08:25,080
EASY ANSWER, I FEEL PRETTY EARLY

4264
03:08:25,080 --> 03:08:26,200
ON, IT IS THE CONTENT OF THE

4265
03:08:26,200 --> 03:08:29,440
EXOSOME AND WHAT IS IN THERE. 

4266
03:08:29,440 --> 03:08:30,760
THAT IS WHY WE NEED TO

4267
03:08:30,760 --> 03:08:31,680
UNDERSTAND SOME FACTORS IN THE

4268
03:08:31,680 --> 03:08:33,040
EXOSOME ARE PUT IN THE EXOSOME

4269
03:08:33,040 --> 03:08:34,520
AND SECRETED BY THAT CELL AND

4270
03:08:34,520 --> 03:08:36,400
ENVIRONMENT AT THAT TIME. THAT

4271
03:08:36,400 --> 03:08:37,880
MEANS WE NEED TO REVISIT THAT

4272
03:08:37,880 --> 03:08:39,040
PART OF OUR UNDERSTANDING OF

4273
03:08:39,040 --> 03:08:40,440
SOME OF THE MECHANISMS THAT WE

4274
03:08:40,440 --> 03:08:42,760
ARE LOOKING AT. I THINK JUST

4275
03:08:42,760 --> 03:08:44,560
LOOKING AT SURFACE MARKERS OF

4276
03:08:44,560 --> 03:08:45,800
THE EXOSOME WILL BE ENOUGH

4277
03:08:45,800 --> 03:08:48,200
BECAUSE IT IS ABOUT THE CONTENT

4278
03:08:48,200 --> 03:08:50,920
MORE. WE ARE TOO EARLY A PHASE,

4279
03:08:50,920 --> 03:08:52,240
MAYBE MY UNDERSTANDING IS TOO

4280
03:08:52,240 --> 03:08:55,560
LIMITED TO BE ABLE TO SAY WHAT

4281
03:08:55,560 --> 03:08:57,080
THE ROLE OF THAT EXOSOME IS

4282
03:08:57,080 --> 03:09:00,200
GOING TO BE IN THE BIOLOGICAL

4283
03:09:00,200 --> 03:09:02,080
SYSTEM, IT'S SECRETED IN. WE

4284
03:09:02,080 --> 03:09:03,880
NEED TO WORK ON THAT BEFORE WE

4285
03:09:03,880 --> 03:09:06,600
CHARACTERIZE THEM WELL ENOUGH. 

4286
03:09:06,600 --> 03:09:08,360
HAPPY TO ENTERTAIN INPUT FROM

4287
03:09:08,360 --> 03:09:12,560
OTHER EXPERTS ON THE PANEL

4288
03:09:12,560 --> 03:09:17,600
TODAY. I DO THINK THAT ONE WAY

4289
03:09:17,600 --> 03:09:20,640
OF IMPROVING OUR UNDERSTANDING

4290
03:09:20,640 --> 03:09:22,640
OF FUNCTION IS WE CAN USE

4291
03:09:22,640 --> 03:09:24,440
CONTROL ENVIRONMENT SUCH AS

4292
03:09:24,440 --> 03:09:26,000
VARIATION OF SYNOVIAL FLUID,

4293
03:09:26,000 --> 03:09:29,200
VARIATIONS OF MSC POPULATIONS,

4294
03:09:29,200 --> 03:09:31,080
STUDYING THEIR EXOSOME RESPONSE

4295
03:09:31,080 --> 03:09:33,440
FROM DEFINABLE CHALLENGES AND

4296
03:09:33,440 --> 03:09:35,880
THERE IS EXCITING WORK DONE IN

4297
03:09:35,880 --> 03:09:39,520
VANDERBILT AND OTHERS, ALSO IN

4298
03:09:39,520 --> 03:09:41,160
ASIA, THE PROGRESSION IS

4299
03:09:41,160 --> 03:09:43,360
QUICKLY, IT IS STILL TOO EARLY

4300
03:09:43,360 --> 03:09:45,040
TO SAY WE NEED TO DO THIS AND

4301
03:09:45,040 --> 03:09:46,480
THIS AND THIS PANEL. SO THE

4302
03:09:46,480 --> 03:09:48,240
PAPER ON EXOSOMES IS STILL

4303
03:09:48,240 --> 03:09:49,880
PENDING.

4304
03:09:49,880 --> 03:09:53,000
>>IF WE ACCEPT IT EXSOMES

4305
03:09:53,000 --> 03:09:54,880
REPRESENT THE CELL CARGO

4306
03:09:54,880 --> 03:09:56,000
SIGNALING MOLECULE FROM CELLS WE

4307
03:09:56,000 --> 03:09:58,640
GET TO A POINT ONE DAY USING

4308
03:09:58,640 --> 03:10:01,720
EXTRA CELLULAR VESICALES AND NO

4309
03:10:01,720 --> 03:10:02,080
CELLS ANY MORE.

4310
03:10:02,080 --> 03:10:07,120
>>I THINK THE ANSWER
COULD BE

4311
03:10:07,120 --> 03:10:09,680
YES. NOT CERTAIN YET. THAT IS A

4312
03:10:09,680 --> 03:10:11,280
FAVORITE QUOTE. CELLS ARE

4313
03:10:11,280 --> 03:10:12,240
SMARTER THAN SURGEONS AND THAT

4314
03:10:12,240 --> 03:10:14,480
IS WHY I THINK CELL LISTENS TO

4315
03:10:14,480 --> 03:10:16,200
ITS ENVIRONMENT, IT DOES WHAT

4316
03:10:16,200 --> 03:10:17,240
THE ENVIRONMENT SEEMS TO NEED

4317
03:10:17,240 --> 03:10:19,960
AND SECRETE WHAT IS THE

4318
03:10:19,960 --> 03:10:21,400
ENVIRONMENT NEEDS. I ALSO THINK

4319
03:10:21,400 --> 03:10:22,640
THE MOMENT CELLS ARE SMARTER

4320
03:10:22,640 --> 03:10:26,480
THAN SCIENTISTS, YES, IT IS

4321
03:10:26,480 --> 03:10:27,840
POSSIBLE SCOTT AND I THINK WE

4322
03:10:27,840 --> 03:10:30,440
SHOULD BE TRYING TO GO THAT

4323
03:10:30,440 --> 03:10:31,800
DIRECTION. IT WOULD BE THAT YOU

4324
03:10:31,800 --> 03:10:33,240
HAVE AN AS PARTICIPANT OF

4325
03:10:33,240 --> 03:10:35,440
SYNOVIAL FLUID FROM THE PATIENT

4326
03:10:35,440 --> 03:10:37,520
JOINT. YOU CHALLENGE THE MSC

4327
03:10:37,520 --> 03:10:38,760
POPULATION WITH SYNOVIAL AS

4328
03:10:38,760 --> 03:10:40,320
PARTICIPANT AND WE CAPTURE THE

4329
03:10:40,320 --> 03:10:42,480
EXOSOMES THAT SECRETES AND APPLY

4330
03:10:42,480 --> 03:10:46,640
THOSE TO PATIENTS KNEE OR OTHER

4331
03:10:46,640 --> 03:10:50,480
JOINTS. MIGHT BE SOMETHING MORE

4332
03:10:50,480 --> 03:10:50,920
CREATIVE.

4333
03:10:50,920 --> 03:10:54,760
>>I THINK WE STILL NEED
TO KNOW

4334
03:10:54,760 --> 03:10:58,080
WHAT IS IN THE EXOSOMES AND HOW

4335
03:10:58,080 --> 03:11:00,800
THAT MIGHT CHANGE WITH THE

4336
03:11:00,800 --> 03:11:02,200
PATIENT OR THE CELL PRODUCING

4337
03:11:02,200 --> 03:11:08,440
IT. MUCH LIKE UPS OR FEDEX TRUCK

4338
03:11:08,440 --> 03:11:09,640
DRIVING DOWN THE ROAD AND WE

4339
03:11:09,640 --> 03:11:12,960
HAVE PACKAGES IN THEM, MAYBE

4340
03:11:12,960 --> 03:11:14,840
ONLY ONE OR TWO DESIGNATED FOR

4341
03:11:14,840 --> 03:11:16,480
YOU OR THAT YOU WANT TO HAVE

4342
03:11:16,480 --> 03:11:20,600
OPEN.

4343
03:11:20,600 --> 03:11:22,720
>>MOST -- NEIGHBOR AT THE

4344
03:11:22,720 --> 03:11:26,120
CORNER HAD NINE BOXES EVERY DAY 

4345
03:11:26,120 --> 03:11:28,560
>>THANK YOU. LOOKING AND
IF

4346
03:11:28,560 --> 03:11:32,320
THERE IS NO FURTHER QUESTIONS WE

4347
03:11:32,320 --> 03:11:42,840
CAN MOVE TO DR. GUILAK'S TALK. 

4348
03:11:43,360 --> 03:11:45,240
FARSHID IS WELL KNOWN, THE

4349
03:11:45,240 --> 03:11:47,360
PROFESSOR OF ORTHOPEDIC SURGERY

4350
03:11:47,360 --> 03:11:50,040
WASU AND DIRECTOR OF RESEARCH

4351
03:11:50,040 --> 03:11:54,520
FOR THE ST. LOUIS SHRINERS

4352
03:11:54,520 --> 03:11:58,520
HOSPITAL. HE HAS WON THREE KAPPA

4353
03:11:58,520 --> 03:12:00,080
DELTA AWARDS AND RECENTLY

4354
03:12:00,080 --> 03:12:02,400
ELECTED TO THE NATIONAL ACADEMY

4355
03:12:02,400 --> 03:12:12,920
OF ENGINEERING. HIS

4356
03:12:12,920 --> 03:12:17,840
CONTRIBUTIONS TO MECHANOBIOLOGY

4357
03:12:17,840 --> 03:12:18,880
AND MECHANIC KNOW MEDICINE,

4358
03:12:18,880 --> 03:12:21,080
LOOKING FORWARD TO YOUR

4359
03:12:21,080 --> 03:12:24,440
DISCUSSION ON GENE EDITING FOR

4360
03:12:24,440 --> 03:12:24,880
ARTHRITIS.

4361
03:12:24,880 --> 03:12:26,480
>>THANK YOU DR. CHU AND

4362
03:12:26,480 --> 03:12:27,640
ORGANIZERS FOR THIS FANTASTIC

4363
03:12:27,640 --> 03:12:35,000
SYMPOSIUM SO FAR. THERE'S BEEN A

4364
03:12:35,000 --> 03:12:37,600
NUMBER OF CELL BASED THERAPIES

4365
03:12:37,600 --> 03:12:41,760
FOR VARIOUS FORMS OF ARTHRITIS,

4366
03:12:41,760 --> 03:12:42,320
MOSTLY IN TRY THOUGHT TREAT

4367
03:12:42,320 --> 03:12:43,600
FOLKAL DEFECT, LESS SO

4368
03:12:43,600 --> 03:12:45,440
RHEUMATOID ARTHRITIS, AS WE HEAR

4369
03:12:45,440 --> 03:12:47,400
TODAY VARIOUS APPROACHES FOR

4370
03:12:47,400 --> 03:12:49,720
OSTEOARTHRITIS.  IN PARTICULAR,

4371
03:12:49,720 --> 03:12:52,920
THESE FORMS OF ARTHRITIS ARE

4372
03:12:52,920 --> 03:12:54,280
VERY IMPORTANT TARGET BECAUSE

4373
03:12:54,280 --> 03:12:58,280
HOW DEBILITATING THEY ARE, THIS

4374
03:12:58,280 --> 03:12:59,440
PATIENT ON THE RIGHT WAS GOT A

4375
03:12:59,440 --> 03:13:01,960
HIP REPLACEMENTED AGE 18 AND

4376
03:13:01,960 --> 03:13:04,520
SECOND HIP ON THE BOTTOM AGE 22,

4377
03:13:04,520 --> 03:13:06,160
HE NEEDS A JOINT REPLACEMENT SO

4378
03:13:06,160 --> 03:13:07,960
ANYTHING WE CAN DO TO TRY TOLL

4379
03:13:07,960 --> 03:13:09,720
PRESERVE JOINTS LIKE THIS, IN

4380
03:13:09,720 --> 03:13:12,840
THE KNEE OR THE HIP OR OTHER

4381
03:13:12,840 --> 03:13:15,320
JOINTS BECAUSE OF THE DISABILITY

4382
03:13:15,320 --> 03:13:18,520
CAUSED COULD BE VERY IMPORTANT. 

4383
03:13:18,520 --> 03:13:20,200
WE HEARD STEM CELL THERAPIES AND

4384
03:13:20,200 --> 03:13:24,480
DR. RODEO GAVE A BACKGROUND. I

4385
03:13:24,480 --> 03:13:27,880
PUT FORTH THAT ALL STEM CELL

4386
03:13:27,880 --> 03:13:29,560
THERAPIES ARE NEITHER STEM CELLS

4387
03:13:29,560 --> 03:13:36,280
NOR THERAPIES. Z WHAT IS OFFERED

4388
03:13:36,280 --> 03:13:38,320
ARE CELLS EVEN IF THEY ARE

4389
03:13:38,320 --> 03:13:41,240
CELLS, JUST A MIX OF DIFFERENT

4390
03:13:41,240 --> 03:13:43,640
TYPES OF NON-STEM CELLS,

4391
03:13:43,640 --> 03:13:44,120
NON-THERAPEUTIC CELLS

4392
03:13:44,120 --> 03:13:47,120
>>BEING ADVERTISED AS YOU
SEE

4393
03:13:47,120 --> 03:13:48,240
SPECIALIZED CELLS THAT KNOW WHAT

4394
03:13:48,240 --> 03:13:51,080
YOU NEED, WHERE YOU NEED IT,

4395
03:13:51,080 --> 03:13:53,520
AUTOMATICALLY GO WILL, BECOME

4396
03:13:53,520 --> 03:13:55,680
IT, THEY SOLVE EVERYTHING AND

4397
03:13:55,680 --> 03:13:58,280
TURNED OUT UNTRUTHFUL, THESE

4398
03:13:58,280 --> 03:13:59,680
CELLS DON'T HOME TO SITE OF

4399
03:13:59,680 --> 03:14:00,760
INJURY, THEY DON'T DO EXACTLY

4400
03:14:00,760 --> 03:14:02,080
WHAT THEY NEED TO DO. AND THEY

4401
03:14:02,080 --> 03:14:03,680
ARE GOING -- THERE HAVE BEEN A

4402
03:14:03,680 --> 03:14:06,000
NUMBER OF REPORTS OF OFF TARGET

4403
03:14:06,000 --> 03:14:07,120
EFFECTS OF CELL INJECTION SO

4404
03:14:07,120 --> 03:14:10,080
THEY ARE NOT HARMLESS, THEY CAN

4405
03:14:10,080 --> 03:14:15,560
HAVE CASES OF OVERGROWTH AND

4406
03:14:15,560 --> 03:14:18,120
HYPERPLASIA HIGH PER TROPHY

4407
03:14:18,120 --> 03:14:19,440
OSSIFICATION IS COMMON IN

4408
03:14:19,440 --> 03:14:21,120
CARTILAGE REPAIR AND MEDICAL

4409
03:14:21,120 --> 03:14:23,440
TOURISM LIKE A MUCOUS PRODUCING

4410
03:14:23,440 --> 03:14:25,840
NOSE LIKE ORGAN OR TUMOR

4411
03:14:25,840 --> 03:14:28,400
FORMATION AND VERY BAD CASE OF

4412
03:14:28,400 --> 03:14:29,400
COMPLETE VISION LOSS IN PATIENTS

4413
03:14:29,400 --> 03:14:31,320
FEW YEARS AG AGO. ONE BIGGEST IE

4414
03:14:31,320 --> 03:14:33,080
WE HAVE IN OUR FIELD IS THERE

4415
03:14:33,080 --> 03:14:35,400
ARE VERY FEW PROSPECTIVE

4416
03:14:35,400 --> 03:14:36,320
RANDOMIZE TRIALS PERFORMED AND

4417
03:14:36,320 --> 03:14:38,520
THIS WAS ALLUDED EARLIER, MANY

4418
03:14:38,520 --> 03:14:40,200
STUDIES DON'T HAVE CONTROL

4419
03:14:40,200 --> 03:14:42,920
GROUPS. WE SAW FROM SOME DATA

4420
03:14:42,920 --> 03:14:44,080
PRESENTED, SOME ARE DOSE

4421
03:14:44,080 --> 03:14:46,080
RESPONSES WITHOUT A PLACEBO

4422
03:14:46,080 --> 03:14:49,160
GROUP.  UNFORTUNATE LITTLENESSES

4423
03:14:49,160 --> 03:14:50,000
HALF STEM CELL CLINICAL TRIALS

4424
03:14:50,000 --> 03:14:58,640
ARE EVER PUBLISHED.  STEM CELLS

4425
03:14:58,640 --> 03:15:00,960
REGARDED INFLAMMATORY RESPONSE

4426
03:15:00,960 --> 03:15:03,840
COMMON TO ARTHRITIS INCLUDING

4427
03:15:03,840 --> 03:15:04,960
OSTEOARTHRITISST OSTEOARTHRITIS,

4428
03:15:04,960 --> 03:15:07,440
RHEUMATOID ARTHRITIS DRIVEN BY

4429
03:15:07,440 --> 03:15:10,640
KEY CYTOKINES COMMON INTERLEUKIN

4430
03:15:10,640 --> 03:15:14,480
1, TNF ALPHA, INTERLEUKIN 6 AND

4431
03:15:14,480 --> 03:15:24,920
MAYBE 17 IN CERTAIN CASES.  WE

4432
03:15:24,920 --> 03:15:27,880
MAY HEAR MORE ABOUT DRUG

4433
03:15:27,880 --> 03:15:29,760
DELIVERY BUT THE PROBLEM IS

4434
03:15:29,760 --> 03:15:31,000
CLEARANCE AND DELIVERY TO JOINT

4435
03:15:31,000 --> 03:15:33,320
AND CARTILAGE IF THAT'S THE

4436
03:15:33,320 --> 03:15:38,080
TARGET. WE HAVE MANY TARGET IN

4437
03:15:38,080 --> 03:15:40,600
OA BUT ONE THAT'S ATTEMPTED IS

4438
03:15:40,600 --> 03:15:45,840
INHIBITOR OF INTERLEUKIN 1

4439
03:15:45,840 --> 03:15:47,840
ANAKINRA OR AND IT HAS A SHORT

4440
03:15:47,840 --> 03:15:50,360
HALF LIFE OF TWO HOURS IN THE

4441
03:15:50,360 --> 03:15:53,360
JOINT AND THERE'S BEEN SOME

4442
03:15:53,360 --> 03:15:56,160
EVIDENCE TO SAY HELPFUL IN RA,

4443
03:15:56,160 --> 03:16:00,600
EVEN EARLY PTOA FOLLOWING ACL

4444
03:16:00,600 --> 03:16:02,600
ENTRY BUT LONG TERM STUDIES

4445
03:16:02,600 --> 03:16:05,880
DIDN'T SHOW SUCCESS.  INCREDIBLE

4446
03:16:05,880 --> 03:16:10,080
STUDY RECENTLY WITH THE

4447
03:16:10,080 --> 03:16:14,360
(INAUDIBLE) TRIAL, IL 1 BETA

4448
03:16:14,360 --> 03:16:15,280
ANTIBODY, 10,000 PATIENTS

4449
03:16:15,280 --> 03:16:17,680
STUDIED WITH THROMBOSIS. POST

4450
03:16:17,680 --> 03:16:19,480
HOC THEYNALSIS, THERE WAS A

4451
03:16:19,480 --> 03:16:22,640
SIGNIFICANT REDUCTION OF 40% HAD

4452
03:16:22,640 --> 03:16:24,080
RATIO OF .58 FOR JOINT

4453
03:16:24,080 --> 03:16:27,960
REPLACEMENT. SUGGESTING THAT IF

4454
03:16:27,960 --> 03:16:30,960
POTENTIALLY DELIVERED PROPERLY,

4455
03:16:30,960 --> 03:16:34,640
COMPOUND SUCH AS INHIBITOR OF

4456
03:16:34,640 --> 03:16:35,880
INTERLEUKIN 1 COULD BE TREATMENT

4457
03:16:35,880 --> 03:16:37,640
FOR OSTEOARTHRITIS. THIS WAS NOT

4458
03:16:37,640 --> 03:16:39,640
THE MAIN GOAL STUDY SO MORE WORK

4459
03:16:39,640 --> 03:16:40,640
NEEDED TO DETERMINE THIS BUT

4460
03:16:40,640 --> 03:16:44,640
THIS IS ONE LARGE EFFECT SIZE

4461
03:16:44,640 --> 03:16:45,840
EVER SEEN IN OSTEOARTHRITIS

4462
03:16:45,840 --> 03:16:51,760
RELATED STUDY.  WHY CAN'T MSC BE

4463
03:16:51,760 --> 03:16:56,360
ABLE TO DO THIS? MAJOR

4464
03:16:56,360 --> 03:16:58,800
ADVANTAGES IN BONE MARROW OR

4465
03:16:58,800 --> 03:17:01,560
ADIPOSE READILY ACCESSIBLE

4466
03:17:01,560 --> 03:17:05,520
MULTI-POTENT CAPABILITY BUT VERY

4467
03:17:05,520 --> 03:17:06,800
POOR HOMING RETENTION IF

4468
03:17:06,800 --> 03:17:08,400
INJECTED, LIMITED UNCONTROL

4469
03:17:08,400 --> 03:17:10,000
THERAPEUTIC RESPONSES WHICH ARE

4470
03:17:10,000 --> 03:17:13,120
QUITE WEAK FROM

4471
03:17:13,120 --> 03:17:15,520
ANTI-INFLAMMATORY STANDPOINT.

4472
03:17:15,520 --> 03:17:17,560
DIFFERENTIATE WITHOUT DIRECT

4473
03:17:17,560 --> 03:17:19,560
QUEUES OR CONTEXT OR MATRICES,

4474
03:17:19,560 --> 03:17:21,440
ONE ISSUE IS VARIABILITY, THERE

4475
03:17:21,440 --> 03:17:23,840
IS SOME DISCUSSION FROM DR.

4476
03:17:23,840 --> 03:17:26,520
ROBEY IN THE CHAT SINGLE CELL

4477
03:17:26,520 --> 03:17:28,160
ANALYSIS. BUNCH OF SINGLE CELL

4478
03:17:28,160 --> 03:17:31,480
ANALYSIS ON BONE MARROW MSC

4479
03:17:31,480 --> 03:17:35,120
ADIPOSE DEFINED BY VARIOUS

4480
03:17:35,120 --> 03:17:36,560
ISOLATION PROCEDURES. NOT ONE

4481
03:17:36,560 --> 03:17:40,360
CELL TYPE THERE, MIX OF 2 TO 7,

4482
03:17:40,360 --> 03:17:43,080
SOMETIMES TEN CELL POPULATIONS

4483
03:17:43,080 --> 03:17:46,280
IN THIS PLOT SINGLE CELL

4484
03:17:46,280 --> 03:17:48,840
ANALYSIS. PURPORTEDLY LESS THAN

4485
03:17:48,840 --> 03:17:50,440
ONE IN TEN THOUSAND ARE STEM

4486
03:17:50,440 --> 03:17:55,960
CELLS WE CALL MSCs.  THE OTHER

4487
03:17:55,960 --> 03:17:57,680
TOPIC WAS THAT OF INFLAMMATION

4488
03:17:57,680 --> 03:17:59,040
AND RESOLVING INFLAMMATION. WE

4489
03:17:59,040 --> 03:18:01,160
NEED INFLAMMATION FOR WOUND

4490
03:18:01,160 --> 03:18:03,600
REPAIR AND TISSUE REPAIR BUT WE

4491
03:18:03,600 --> 03:18:05,960
NEED TO FORM INFLAMMATION THAT

4492
03:18:05,960 --> 03:18:08,160
RESOLVES SO INITIAL ONSET OF

4493
03:18:08,160 --> 03:18:11,240
INFLAMMATION AND RESPONSE TO

4494
03:18:11,240 --> 03:18:12,840
WOUND, RESOLUTION PHASE AND POST

4495
03:18:12,840 --> 03:18:14,720
RESOLUTION PHASE WHERE ADAPTIVE

4496
03:18:14,720 --> 03:18:15,600
IMMUNE CELLS CAN CLEAN THINGS

4497
03:18:15,600 --> 03:18:18,080
UP. THE PROBLEM IS NOT RESOLVING

4498
03:18:18,080 --> 03:18:18,880
INFLAMMATION, BUT CHRONIC

4499
03:18:18,880 --> 03:18:21,640
INFLAMMATION.  THIS IS PRESENT

4500
03:18:21,640 --> 03:18:23,280
IN MANY FORMS OF ARTHRITIS OR

4501
03:18:23,280 --> 03:18:26,400
INJURY. OBESITY AS RISK FACTOR

4502
03:18:26,400 --> 03:18:28,680
FOR ARTHRITIS, WHERE LEVELS OF

4503
03:18:28,680 --> 03:18:32,200
CYTOKINES ARE CONTINUOUSLY HIGH.

4504
03:18:32,200 --> 03:18:35,000
NOT ONLY HIGH BUT IN FLAIRS

4505
03:18:35,000 --> 03:18:36,960
THESE CAN BE DIE YOUR HONORRAL

4506
03:18:36,960 --> 03:18:38,760
OR CIRCADIAN ON DAILY BASIS OR

4507
03:18:38,760 --> 03:18:40,080
ENVIRONMENTALLY TRIGGERED AND

4508
03:18:40,080 --> 03:18:42,280
DRUG THERAPIES CURRENTLY FOR

4509
03:18:42,280 --> 03:18:44,080
RHEUMATOID ARTHRITIS ARE HIGH

4510
03:18:44,080 --> 03:18:46,480
LEVEL PROTEIN THERAPIES.

4511
03:18:46,480 --> 03:18:49,280
SUPPRESS THE IMMUNE RESPONSE AND

4512
03:18:49,280 --> 03:18:51,440
NUMBER OF SIDE EFFECT INCREASE

4513
03:18:51,440 --> 03:18:57,440
INFECTION RISK.  WE WILL HEAR

4514
03:18:57,440 --> 03:19:00,440
PROTEIN DELIVERY WORKING WELL IN

4515
03:19:00,440 --> 03:19:02,520
CERTAIN CASES MASSIVE RESEARCH

4516
03:19:02,520 --> 03:19:04,280
BUT WHERE IT FAILS ARE THINGS

4517
03:19:04,280 --> 03:19:08,360
LIKE I DESCRIBED, HIGH LEVELS

4518
03:19:08,360 --> 03:19:10,600
ANTI-CYTOKINE BIOLOGIC DRUGS

4519
03:19:10,600 --> 03:19:12,520
THAT RESPOND TO STIMULUS LIKE

4520
03:19:12,520 --> 03:19:15,760
ENVIRONMENTAL TRIGGER OR

4521
03:19:15,760 --> 03:19:17,440
CIRCADIAN TRIGGER HAVE RAPID

4522
03:19:17,440 --> 03:19:18,640
RESPONSE TIMES OF MINUTES TO

4523
03:19:18,640 --> 03:19:20,640
HOURS AND BE THERE AND BE

4524
03:19:20,640 --> 03:19:22,680
DELIVERED FOR MONTHS OR YEARS.

4525
03:19:22,680 --> 03:19:24,640
ONE REASON EXOSOMES ARE NOT LONG

4526
03:19:24,640 --> 03:19:26,840
TERM DELIVERY INSTEAD OF CELLS

4527
03:19:26,840 --> 03:19:29,000
IS CELLS CAN DELIVER

4528
03:19:29,000 --> 03:19:30,120
CONTINUOUSLY DRUGS FOR LONG TIME

4529
03:19:30,120 --> 03:19:36,360
EXOSOMES AS WE SAW POTENTIAL

4530
03:19:36,360 --> 03:19:37,040
STRENGTH DELIVERED REPEATEDLY

4531
03:19:37,040 --> 03:19:39,920
AND OVER AND OVER.  WE THINK

4532
03:19:39,920 --> 03:19:42,680
ABOUT THIS, OUR GOAL WAS TO

4533
03:19:42,680 --> 03:19:44,240
DEVELOP TECHNIQUES TO CREATE

4534
03:19:44,240 --> 03:19:46,240
SMARTER CELLS THAN WE JUST HEARD

4535
03:19:46,240 --> 03:19:48,240
ABOUT. TO USE SYNTHETIC BIOLOGY

4536
03:19:48,240 --> 03:19:51,200
TO CREATE CELLS THAT CAN

4537
03:19:51,200 --> 03:19:53,000
SELF-REGULATE PROVIDE

4538
03:19:53,000 --> 03:19:53,640
APPROPRIATE DRUGS APPROPRIATE

4539
03:19:53,640 --> 03:19:55,800
TIMES IN RESPONSE TO STIMULI.

4540
03:19:55,800 --> 03:19:59,200
THINK ABOUT DRUG DELIVERY AND

4541
03:19:59,200 --> 03:20:02,240
PROTEIN, IT IS HAVING A LEAKY

4542
03:20:02,240 --> 03:20:03,720
BUCKET OF DRUGS, PATIENT SIDE

4543
03:20:03,720 --> 03:20:05,480
THE BODY, THE DRUG LEAKS OUT AND

4544
03:20:05,480 --> 03:20:08,440
WHEN FINISHED REPLACE THE BUCK

4545
03:20:08,440 --> 03:20:12,520
OR REFILL WHICH MANY CASES WILL

4546
03:20:12,520 --> 03:20:16,160
WORK. IF YES USE GENE THERAPY

4547
03:20:16,160 --> 03:20:18,320
APPROACHES, WITH CONSTITUTIVE

4548
03:20:18,320 --> 03:20:19,800
PROMOTER WE HAVE LARGE AMOUNTS

4549
03:20:19,800 --> 03:20:22,000
OF DRUG GUSHING OUT. IN CERTAIN

4550
03:20:22,000 --> 03:20:24,520
CASES SUCH AS HEMOPHILIA, THIS

4551
03:20:24,520 --> 03:20:28,160
MAYBE A GOOD APPROACH. GENE

4552
03:20:28,160 --> 03:20:29,600
THERAPIES WITH INDUCIBLE

4553
03:20:29,600 --> 03:20:31,200
PROMOTERS LIKE HAVING A FAUCET

4554
03:20:31,200 --> 03:20:34,200
YOU CAN TURN ON AND OFF, BUT

4555
03:20:34,200 --> 03:20:36,200
NEED TO KNOW WHEN TO TURN ON AND

4556
03:20:36,200 --> 03:20:40,840
OFF TO FIGHT INFLAMMATION.  A

4557
03:20:40,840 --> 03:20:43,400
CELL HAS A SENSOR, DELIVER DRUGS

4558
03:20:43,400 --> 03:20:51,920
WHEN IT SENSES ANY OTHER

4559
03:20:51,920 --> 03:20:54,600
TRIGGTRIGGER. WE THOUGHT WE CANE

4560
03:20:54,600 --> 03:20:57,760
A CELL LOOK AT RECEPTORS,

4561
03:20:57,760 --> 03:21:00,240
INTERNAL GENE CIRCUITS AND

4562
03:21:00,240 --> 03:21:01,560
APPROPRIATE OUTPUT PATHWAYS

4563
03:21:01,560 --> 03:21:03,680
WHETHER CYTOKINE INHIBITORS PAIN

4564
03:21:03,680 --> 03:21:07,320
TARGETS OR ANABOLIC FACTORS, AND

4565
03:21:07,320 --> 03:21:10,520
REPROGRAM USING CRISPER CAS 9

4566
03:21:10,520 --> 03:21:14,000
ENGINEERING IN IPSCs IN OUR

4567
03:21:14,000 --> 03:21:18,320
CASE. DEVELOP CELLS WITH

4568
03:21:18,320 --> 03:21:19,200
INFLAMMATORY RESPONSE, WE CAN

4569
03:21:19,200 --> 03:21:21,200
COME IN TO LEAK IT ON GENETIC

4570
03:21:21,200 --> 03:21:22,960
BASIS IN ITS PLACE PUT FEEDBACK

4571
03:21:22,960 --> 03:21:26,520
LOOP TO CREATE BIOLOGIC DRUGS. 

4572
03:21:26,520 --> 03:21:29,080
IT IS REPROGRAMMABLE CELL LIKE

4573
03:21:29,080 --> 03:21:30,920
iPHONE YOU PUT THESE LITTLE

4574
03:21:30,920 --> 03:21:32,680
APPS INTO THE iPHONE AND APPS

4575
03:21:32,680 --> 03:21:35,680
ARE DESIGNED TO DELIVER WHAT WE

4576
03:21:35,680 --> 03:21:41,040
NEED DELIVERED.  FIRST WORK DONE

4577
03:21:41,040 --> 03:21:43,000
BY GRADUATE STUDENT JONATHAN ON

4578
03:21:43,000 --> 03:21:44,320
FACULTY AT VANDERBILT, HE

4579
03:21:44,320 --> 03:21:50,960
DEVELOPED IL 1 AND TNF RESPONSE

4580
03:21:50,960 --> 03:21:54,560
SYNTHETIC CIRCUITS. ACTED BY

4581
03:21:54,560 --> 03:21:58,200
CYTOKINES HE THEN LOOKED AT

4582
03:21:58,200 --> 03:21:59,560
EFFECTOR GENES AND IN THIS CASE

4583
03:21:59,560 --> 03:22:04,800
FOUND CCL 2 WAS ONE OF THE BEST

4584
03:22:04,800 --> 03:22:07,880
MARKERS OF TNF OR IL 1 ACTIVITY

4585
03:22:07,880 --> 03:22:09,320
OUTSIDE THE CELL. FROM THAT HE

4586
03:22:09,320 --> 03:22:11,640
WAS ABLE TO BUILD SYNTHETIC GENE

4587
03:22:11,640 --> 03:22:13,880
CIRCUIT WITH TNF RECEPTOR OR IL

4588
03:22:13,880 --> 03:22:16,840
1 AS TARGET. WHEN IT WAS

4589
03:22:16,840 --> 03:22:19,280
ACTIVATED AND CRL 2 WAS

4590
03:22:19,280 --> 03:22:21,440
ACTIVATED, ALSO TOOK ONE ALLELE

4591
03:22:21,440 --> 03:22:23,840
AND CREATED THE INHIBITOR DRUG

4592
03:22:23,840 --> 03:22:34,360
FOR TNF OR IL 1 AS THE OUTPUT. 

4593
03:22:36,040 --> 03:22:41,040
INSERT TNF -- WHEN THE CELLS SEE

4594
03:22:41,040 --> 03:22:44,600
TNF INSTEAD OF TWO COPIES OF CCL

4595
03:22:44,600 --> 03:22:46,240
2, IT MAKE IT IS INHIBITOR WHICH

4596
03:22:46,240 --> 03:22:47,960
GOES BACK AND BLOCKS TNF

4597
03:22:47,960 --> 03:22:49,320
ACTIVITY. WHEN WE DO THIS

4598
03:22:49,320 --> 03:22:50,560
EVERYTHING WORKED IN H VITRO AND

4599
03:22:50,560 --> 03:23:00,640
MORE RECENTLY TESTED THIS IN A

4600
03:23:00,640 --> 03:23:02,120
MODEL OF RHEUMATOID ARTHRITIS,

4601
03:23:02,120 --> 03:23:05,040
MOLECULES SUCH AS IL 1 TNF ARE

4602
03:23:05,040 --> 03:23:05,800
IMPORTANTOR IMPORTANT PLAYERS. 

4603
03:23:05,800 --> 03:23:07,480
TO KEEP CELLS IN PLACE THEY WERE

4604
03:23:07,480 --> 03:23:09,960
ENGINEERED TO A SMALL DISC OF

4605
03:23:09,960 --> 03:23:12,680
CARTILAGE WHERE THEY SAT

4606
03:23:12,680 --> 03:23:13,600
SUBCUTANEOUSLY SINCE THE

4607
03:23:13,600 --> 03:23:16,360
ENVIRONMENT FOR INFLAMMATION AND

4608
03:23:16,360 --> 03:23:26,400
DELIVERED DRUGS SYSTEMICALLY

4609
03:23:26,400 --> 03:23:28,200
THEY SHOWED NICELY HAVING DRUG

4610
03:23:28,200 --> 03:23:30,160
DELIVERY IN THIS ON DEMAND

4611
03:23:30,160 --> 03:23:32,520
SYSTEM, COULD ALLEVIATE PAIN

4612
03:23:32,520 --> 03:23:34,760
SENSITIVITY, RED IS TREATED

4613
03:23:34,760 --> 03:23:36,520
GROUP, INCREASED OR DECREASE

4614
03:23:36,520 --> 03:23:39,200
PAIN THRESHOLD IN THE CONTROL

4615
03:23:39,200 --> 03:23:40,440
AND CONTROL TREATED GROUPS

4616
03:23:40,440 --> 03:23:50,960
SIGNIFICANTLY INCREASED. ON AN

4617
03:23:54,240 --> 03:23:57,920
ON DEMAND BASIS. WE SAW COMPLETE

4618
03:23:57,920 --> 03:23:59,920
-- NEVER ACCOMPLISHED BY DRUG

4619
03:23:59,920 --> 03:24:01,160
THERAPIES IN RHEUMATOID

4620
03:24:01,160 --> 03:24:02,680
ARTHRITIS.  WE USE IT AS A MODEL

4621
03:24:02,680 --> 03:24:06,520
BECAUSE WE KNOW THE INFLAMMATORY

4622
03:24:06,520 --> 03:24:08,000
TARGETS SO WELL STILL NEED TO

4623
03:24:08,000 --> 03:24:11,320
IDENTIFY IN OSTEOARTHRITIS. WE

4624
03:24:11,320 --> 03:24:12,880
HAVE NOW SEVERAL OTHER

4625
03:24:12,880 --> 03:24:16,240
APPROACHES USING, iPHONE

4626
03:24:16,240 --> 03:24:18,720
PROGRAM APPS INTO IT, WE HAVE

4627
03:24:18,720 --> 03:24:20,200
APPS BUILT TO FIND OURSELVES OR

4628
03:24:20,200 --> 03:24:24,000
FIND MY iPHONE BY USING

4629
03:24:24,000 --> 03:24:26,800
LUCIFERASE OR GFP, WE CAN TAG

4630
03:24:26,800 --> 03:24:28,400
SIGNAL TO ANTI-CYTOKINE THERAPY

4631
03:24:28,400 --> 03:24:30,960
AND GET SIGNAL INTENSITY. WE CAN

4632
03:24:30,960 --> 03:24:33,520
TURN ON AND OFF SYSTEM

4633
03:24:33,520 --> 03:24:35,880
EXOGENOUSLY, USING THINGS LIKE

4634
03:24:35,880 --> 03:24:38,080
TEAT OFF OR ON SYSTEM SO IF YOU

4635
03:24:38,080 --> 03:24:40,400
TEMPORARILY WANT TO SHUT OFF THE

4636
03:24:40,400 --> 03:24:42,640
GENE CIRCUIT WE CAN DO IT WITH

4637
03:24:42,640 --> 03:24:43,120
TETRA CYCLINE RESPONSIVE

4638
03:24:43,120 --> 03:24:45,760
ELEMENT. THESE ARE IPSCs TRUE

4639
03:24:45,760 --> 03:24:48,400
STEM CELLS WITH PLURIPOTENT

4640
03:24:48,400 --> 03:24:51,040
CAPABILITY SO WE CAN BUILD U

4641
03:24:51,040 --> 03:24:52,200
SELF-DESTRUCT SIGNALS IF THEY

4642
03:24:52,200 --> 03:24:53,800
ESCAPE FROM THE CONSTRUCT AND

4643
03:24:53,800 --> 03:24:55,880
NEED TO BE ELIMINATED. MOST

4644
03:24:55,880 --> 03:24:57,600
RECENTLY WE HAVE BEEN TRYING TO

4645
03:24:57,600 --> 03:24:59,600
DEVELOP SYSTEMS THAN CAN

4646
03:24:59,600 --> 03:25:02,040
DISTINGUISH DIFFERENT CYTOKINES

4647
03:25:02,040 --> 03:25:03,640
AND RESPONSES BECAUSE AS WE

4648
03:25:03,640 --> 03:25:05,520
HEARD EARLIER THERE, IS NO ONE

4649
03:25:05,520 --> 03:25:06,320
ANTI-CYTOKINE THERAPY THAT IS

4650
03:25:06,320 --> 03:25:08,520
GOING TO TREAT ALL THE DISEASE

4651
03:25:08,520 --> 03:25:13,840
OR ALL OA, WE CAN IDENTIFY

4652
03:25:13,840 --> 03:25:17,080
FINGERPRINTS USING MICRORNA

4653
03:25:17,080 --> 03:25:19,920
SIGNATURES ACTIVATED BY PRESENCE

4654
03:25:19,920 --> 03:25:22,000
OF DIFFERENT CYTOKINES AND WE

4655
03:25:22,000 --> 03:25:23,240
CAN BUILD GENE CIRCUITS BASED ON

4656
03:25:23,240 --> 03:25:25,720
THESE. IN THE LAST FEW MINIS

4657
03:25:25,720 --> 03:25:28,800
WILL TELL YOU ABOUT TWO OTHER

4658
03:25:28,800 --> 03:25:30,200
CIRCUITS WE BUILD THAT HAVE BEEN

4659
03:25:30,200 --> 03:25:33,760
FUN. ONE IS A FORCE RESPONSIVE

4660
03:25:33,760 --> 03:25:36,520
TOUCH SENSOR DELIVERING DRUGS IN

4661
03:25:36,520 --> 03:25:42,040
RESPONSE TO MECHANICAL LOADING.

4662
03:25:42,040 --> 03:25:44,280
ARE MECHANICALLY SENSITIVE. BONE

4663
03:25:44,280 --> 03:25:46,920
GROWS WHEN YOU LOAD IT, MUSCLE

4664
03:25:46,920 --> 03:25:48,280
GROW, CARTILAGE DOES THE SAME

4665
03:25:48,280 --> 03:25:50,360
THING, IT HAS MECHANIC KNOW

4666
03:25:50,360 --> 03:25:52,280
SENSITIVITY, YOU CAN SEE A PIECE

4667
03:25:52,280 --> 03:25:56,320
BEING SUPPRESSED CAUSING CALCIUM

4668
03:25:56,320 --> 03:25:58,400
SIGNAL. WE TRACK DOWN SENSORS ON

4669
03:25:58,400 --> 03:26:01,000
THE CELLS THAT ARE RESPONSIBLE

4670
03:26:01,000 --> 03:26:02,200
FOR MECHANIC KNOW TRANSDUCTION

4671
03:26:02,200 --> 03:26:04,840
AND ISOLATED TO THE FAMILY,

4672
03:26:04,840 --> 03:26:08,040
PARTICULARLY TRIP V 4 AS PRIMARY

4673
03:26:08,040 --> 03:26:09,360
MECHANIC KNOW SENSORS AND

4674
03:26:09,360 --> 03:26:11,320
CARTILAGE. WITH THAT KNOWLEDGE

4675
03:26:11,320 --> 03:26:14,800
WE THEN WENT AND BUILT SYNTHETIC

4676
03:26:14,800 --> 03:26:18,640
GENE CIRCUITS MECHANIC KNOW

4677
03:26:18,640 --> 03:26:20,440
GENETICS H. WE BUILT GENE

4678
03:26:20,440 --> 03:26:21,720
CIRCUITS WHERE MECHANICAL

4679
03:26:21,720 --> 03:26:25,440
LOADING VIA TRIP V 4, TO DO THAT

4680
03:26:25,440 --> 03:26:27,200
WE ISOLATED SIGNALING CHANNELS

4681
03:26:27,200 --> 03:26:28,880
LOOK AT THE MECHANIC KNOW

4682
03:26:28,880 --> 03:26:31,200
TRANSDUCTION PATHWAYS

4683
03:26:31,200 --> 03:26:35,080
DOWNSTREAM, USE BIOINFORMATICS

4684
03:26:35,080 --> 03:26:37,200
AND CHAIRMAN SEQ TO FIND NODE

4685
03:26:37,200 --> 03:26:38,760
AND HUB GENES THAT ACTIVATE

4686
03:26:38,760 --> 03:26:40,640
RESPONSE AND BUILD GENE CIRCUITS

4687
03:26:40,640 --> 03:26:43,480
USING CRISPER OR LENTIVIRAL

4688
03:26:43,480 --> 03:26:46,000
APPROACHES TO TAG DRUG ON TO THE

4689
03:26:46,000 --> 03:26:51,000
MECHANICCAL LOADING PATHWAY.  SO

4690
03:26:51,000 --> 03:26:52,320
GENE ARRAY DATA SHOWING ACT

4691
03:26:52,320 --> 03:26:55,200
VISION OF ION CHANNEL BY

4692
03:26:55,200 --> 03:26:56,200
CHEMICAL OR MECHANICAL MEANS,

4693
03:26:56,200 --> 03:26:58,320
YOU CAN SEE THAT THE RESPONSE IS

4694
03:26:58,320 --> 03:27:02,120
QUALITATIVELY AND QUANTITATIVELY

4695
03:27:02,120 --> 03:27:13,080
SIMILAR FROM CHIPOTLE CHIP SEQ,Y

4696
03:27:13,840 --> 03:27:19,480
POST DOC BOB MIMS AND A STUDENT

4697
03:27:19,480 --> 03:27:21,840
BUILD MECHANIC KNOW SENSITIVE

4698
03:27:21,840 --> 03:27:23,920
MOTIFS, WHERE THEN MECHANICAL

4699
03:27:23,920 --> 03:27:25,840
LOADING ACTIVATE PRODUCTION OF

4700
03:27:25,840 --> 03:27:27,920
OUR DRUG, FAVORITE DRUG IN THIS

4701
03:27:27,920 --> 03:27:30,720
CASE IL 1 RA SO EASY TO MEASURE

4702
03:27:30,720 --> 03:27:33,760
AND DOESN'T DO ANYTHING UNLESS

4703
03:27:33,760 --> 03:27:38,360
IS, UL 1. ONCE WE TRANSDUCE INTO

4704
03:27:38,360 --> 03:27:40,800
EXPLANTS AND CHONDROCYTES AND

4705
03:27:40,800 --> 03:27:43,360
INTO ENGINEER CONSTRUCTS, WE CAN

4706
03:27:43,360 --> 03:27:44,800
SHOW DIFFERENT TIME AND DOSE

4707
03:27:44,800 --> 03:27:46,840
DEPENDENT RESPONSES, THIS IS

4708
03:27:46,840 --> 03:27:49,480
LUCIFERASE ACTIVITY, SHOWING THE

4709
03:27:49,480 --> 03:27:52,800
RESPONSE TO ACTIVATING ION

4710
03:27:52,800 --> 03:27:55,120
CHANNEL WHETHER NF KAPPA B

4711
03:27:55,120 --> 03:28:00,440
RESPONSIVE CIRCUIT OR PT GS 2

4712
03:28:00,440 --> 03:28:03,520
RESPONSIVE CIRCUIT IN TERMS OF

4713
03:28:03,520 --> 03:28:06,720
MAGNITUDE AND DURATION.  WE

4714
03:28:06,720 --> 03:28:08,600
BUILT CIRCUITS WITH PREDEFINED

4715
03:28:08,600 --> 03:28:10,760
RESPONSES OR DRUG DELIVERY,

4716
03:28:10,760 --> 03:28:16,400
DURATIONS AND RECOVERY TIMES.  

4717
03:28:16,400 --> 03:28:18,360
WE ALSO SHOWED WHEN YOU

4718
03:28:18,360 --> 03:28:19,480
MECHANICALLY LOAD THEM YOU CAN

4719
03:28:19,480 --> 03:28:22,480
GET PRODUCTION OF IL 1 RA IN

4720
03:28:22,480 --> 03:28:23,640
RESPONSE TO LOADING WHICH THE

4721
03:28:23,640 --> 03:28:25,360
CELLS DON'T NORMALLY MAKE.

4722
03:28:25,360 --> 03:28:28,880
FINALLY, THE MOST RECENT

4723
03:28:28,880 --> 03:28:34,080
APPROACH IS TO CREATE A CLOCK,

4724
03:28:34,080 --> 03:28:35,120
GENE CIRCUIT BASICALLY ONE BASED

4725
03:28:35,120 --> 03:28:37,000
ON THE CIRCADIAN CLOCK OF THE

4726
03:28:37,000 --> 03:28:39,920
CELL, SO THAT WE CAN DO DIE YOUR

4727
03:28:39,920 --> 03:28:40,720
HONORRAL DRUG DELIVERY.  THIS IS

4728
03:28:40,720 --> 03:28:42,720
IMPORTANT BECAUSE AS I SHOWED

4729
03:28:42,720 --> 03:28:49,200
YOU, FLAVORS FLARES CAN BE DIE R

4730
03:28:49,200 --> 03:28:53,000
HONORRAL AND RECENT AREAS OF --

4731
03:28:53,000 --> 03:28:54,560
DIURNAL, MATCHING DRUG DELIVERY

4732
03:28:54,560 --> 03:28:56,240
TO TIME OF DAY, BECAUSE

4733
03:28:56,240 --> 03:28:57,840
INFLAMMATION GOES UP AND DOWN

4734
03:28:57,840 --> 03:29:01,280
AND FOR EXAMPLE IN RHEUMATOID

4735
03:29:01,280 --> 03:29:02,280
ARTHRITIS PEAK AROUND 3 IN THE

4736
03:29:02,280 --> 03:29:03,880
MORNING RARELY WHEN DRUGS ARE

4737
03:29:03,880 --> 03:29:08,720
GIVEN SO WE LOOK AT THE CORE

4738
03:29:08,720 --> 03:29:10,880
CLOCK GENES IN CHONDROCYTES AND

4739
03:29:10,880 --> 03:29:14,440
THEY HAVE STABLE -- THIS IS A

4740
03:29:14,440 --> 03:29:17,680
MOUSE IN PA DARK INCUBATOR THAT

4741
03:29:17,680 --> 03:29:23,480
PSYCHS A WEEK AFTER TAKEN OUT. 

4742
03:29:23,480 --> 03:29:25,240
YOU CAN SEE IT FLASHING AND

4743
03:29:25,240 --> 03:29:28,320
USING THIS CONCEPT OF

4744
03:29:28,320 --> 03:29:29,360
CHRONOTHERAPY WE CAN EXCITE GENE

4745
03:29:29,360 --> 03:29:30,720
CIRCUITS THAT DELIVER DRUGS AT

4746
03:29:30,720 --> 03:29:32,640
SPECIFIC TIME OF DAY ON THE

4747
03:29:32,640 --> 03:29:35,000
CONTINUING BASIS FOR ARTHRITIS

4748
03:29:35,000 --> 03:29:42,720
TARGETING EARLY MORNING. WE

4749
03:29:42,720 --> 03:29:44,920
CREATED CLOCK GENE CIRCUITS BY

4750
03:29:44,920 --> 03:29:46,760
HR 2 AND OTHER CLOCK COMPONENTS

4751
03:29:46,760 --> 03:29:48,600
DRIVING OUR DRUG, IN FACT

4752
03:29:48,600 --> 03:29:52,160
ENGINEERED TO CARTILAGE Z THESE

4753
03:29:52,160 --> 03:29:55,440
CELLS OSCILLATE ON A 23, 24 HOUR

4754
03:29:55,440 --> 03:29:58,200
BASIS AND SHOWED CIRCADIAN GENE

4755
03:29:58,200 --> 03:30:02,360
EXPRESSION OF OUR DRUG AND

4756
03:30:02,360 --> 03:30:04,160
CIRCADIAN PROTEIN PRODUCTION OF

4757
03:30:04,160 --> 03:30:06,480
DRUG DELIVERY. ONCE IMPLANTED IN

4758
03:30:06,480 --> 03:30:08,400
MICE THEY SYNCHRONIZE WITH THE

4759
03:30:08,400 --> 03:30:11,560
MOUSE AND DELIVER FIVE TIMES

4760
03:30:11,560 --> 03:30:14,880
MORE DRUG DURING THE NIGHT CYCLE

4761
03:30:14,880 --> 03:30:16,600
THAN THE DAY CYCLE. ONE MORE

4762
03:30:16,600 --> 03:30:18,480
EXAMPLE, CONCLUDE THERE AND SAY

4763
03:30:18,480 --> 03:30:20,800
THAT WE CAN TAKE STEM CELLS AND

4764
03:30:20,800 --> 03:30:22,160
MAKE THEM EVEN SENATOR AND

4765
03:30:22,160 --> 03:30:27,600
BETTER BY EDITING THEIR GENOME

4766
03:30:27,600 --> 03:30:29,680
THEIR EPIGENOME, CREATE

4767
03:30:29,680 --> 03:30:31,120
ARTIFICIAL GENE CIRCUITS WITH

4768
03:30:31,120 --> 03:30:33,280
CONTROLLED OUTPUTS, REPACKAGE AS

4769
03:30:33,280 --> 03:30:34,760
GENE THERAPY, CELL THERAPY,

4770
03:30:34,760 --> 03:30:37,680
IMPLANT THERAPIES OR HOPEFULLY

4771
03:30:37,680 --> 03:30:39,080
EVENTUALLY ENTIRE JOINT

4772
03:30:39,080 --> 03:30:41,040
RESURFACING THERAPIES FOR

4773
03:30:41,040 --> 03:30:42,280
VARIOUS FORMS OFFER ARTHRITIS.

4774
03:30:42,280 --> 03:30:43,920
I'LL CONCLUDE THERE, THANKS TO

4775
03:30:43,920 --> 03:30:46,640
COLLABORATORS AN LAB WHO DID

4776
03:30:46,640 --> 03:30:49,680
THIS WORK AND NIH AS WELL AS

4777
03:30:49,680 --> 03:30:52,640
SHRINERS AND ARTHRITIS

4778
03:30:52,640 --> 03:30:56,720
FOUNDATION.  FROM THE

4779
03:30:56,720 --> 03:30:58,160
>>THANK YOU. THANK YOU
FOR THAT

4780
03:30:58,160 --> 03:31:02,440
TOUR INTO THE FUTURE AND SO MANY

4781
03:31:02,440 --> 03:31:06,880
EXCITING CONCEPTS YOU PUT INTO

4782
03:31:06,880 --> 03:31:13,600
RESEARCH AND BROUGHT TO NICE

4783
03:31:13,600 --> 03:31:16,360
STUDIES. I WANTED TO ASK ABOUT

4784
03:31:16,360 --> 03:31:18,240
THE IMPLANT, WHERE YOU HAVE

4785
03:31:18,240 --> 03:31:19,720
ENGINEERED CELLS WITHIN

4786
03:31:19,720 --> 03:31:25,200
CARTILAGE CONSTRUCT. SO WHEN

4787
03:31:25,200 --> 03:31:26,320
PEOPLE INJECT THAT AND OTHER

4788
03:31:26,320 --> 03:31:28,160
THINGS INTO THE BODY IT'S

4789
03:31:28,160 --> 03:31:29,760
RESORBED.  CAN YOU COMMENT HOW

4790
03:31:29,760 --> 03:31:33,080
LONG THIS IMPLANT LASTS AND HOW

4791
03:31:33,080 --> 03:31:36,240
LONG THE CELLS SURVIVAL WITHIN

4792
03:31:36,240 --> 03:31:39,600
THE CARTILAGE MATRIX?

4793
03:31:39,600 --> 03:31:41,840
>>GREAT QUESTION, THE
REASON WE

4794
03:31:41,840 --> 03:31:44,480
USE THAT AS IMPLANT, IT IS

4795
03:31:44,480 --> 03:31:45,920
AVASCULAR AND IT SHIELDS THE

4796
03:31:45,920 --> 03:31:48,440
CELLS, THEY ARE ENCASED SO THEY

4797
03:31:48,440 --> 03:31:50,920
CAN'T CRAWL AWAY. CARTILAGE

4798
03:31:50,920 --> 03:31:52,160
IMPLANTED SUBCUTANEOUSLY LIKE

4799
03:31:52,160 --> 03:31:56,160
THIS OR IN A JOINT, LASTS MONTHS

4800
03:31:56,160 --> 03:31:58,960
OR YEARS. KELSEY COLLINS IN OUR

4801
03:31:58,960 --> 03:32:00,360
GROUP TESTED THIS OUT FOR SIX

4802
03:32:00,360 --> 03:32:01,680
MONTHS SO FAR, WE HAVE SOME THAT

4803
03:32:01,680 --> 03:32:04,760
ARE I THINK STILL GOING. BUT AT

4804
03:32:04,760 --> 03:32:05,960
LEAST SIX MONTHS THOSE ARE JUST

4805
03:32:05,960 --> 03:32:09,400
SITTING THERE AND THEY DON'T GET

4806
03:32:09,400 --> 03:32:12,200
ENCAPSULATED BECAUSE CARTILAGE

4807
03:32:12,200 --> 03:32:13,200
IS NON-STICK AND CELLS DON'T

4808
03:32:13,200 --> 03:32:15,080
ATTACH TO IT AND CAUSE ANY

4809
03:32:15,080 --> 03:32:18,160
PROBLEMS.  SO FOR OUR PURPOSES

4810
03:32:18,160 --> 03:32:19,520
AT LEAST SIX MONTHS IF NOT

4811
03:32:19,520 --> 03:32:22,120
LONGER.

4812
03:32:22,120 --> 03:32:27,080
>>FANTASTIC. LOOKING FOR

4813
03:32:27,080 --> 03:32:28,320
QUESTIONS I WILL ASK ANOTHER

4814
03:32:28,320 --> 03:32:30,120
ONE. I THINK WHAT YOU ARE

4815
03:32:30,120 --> 03:32:36,760
SHOWING IS VERY EXCITING. HOW

4816
03:32:36,760 --> 03:32:40,200
WOULD YOU ENVISION TRANSLATING

4817
03:32:40,200 --> 03:32:43,760
SOME OF THIS IN TO CLINICAL

4818
03:32:43,760 --> 03:32:44,000
PRACTICE?

4819
03:32:44,000 --> 03:32:47,280
>>THAT IS ALSO A --

4820
03:32:47,280 --> 03:32:49,120
>>CLINICAL RESEARCH
FIRST.

4821
03:32:49,120 --> 03:32:51,240
>>WE WON'T SKIP THAT
STEP. THAT

4822
03:32:51,240 --> 03:32:53,080
IS ONE OF OUR BIGGEST CHALLENGES

4823
03:32:53,080 --> 03:32:55,480
IS SCALE UP AND DOSING BECAUSE

4824
03:32:55,480 --> 03:32:57,960
WE NEED TO KNOW EXACTLY HOW MANY

4825
03:32:57,960 --> 03:32:59,320
CELLS WE NEED. THERE ARE ALL

4826
03:32:59,320 --> 03:33:01,200
DIFFERENT WAYS TO CONTROL THE

4827
03:33:01,200 --> 03:33:02,840
OUTPUT BESIDES CELLS NUMBER SO

4828
03:33:02,840 --> 03:33:05,960
WE DON'T WANT TO HAVE IMPLANTS

4829
03:33:05,960 --> 03:33:07,800
HUGE BUT THERE IS GOOD EVIDENCE

4830
03:33:07,800 --> 03:33:11,440
FOR HAVING LONG TERM BIOMATERIAL

4831
03:33:11,440 --> 03:33:13,120
IMPLANTS IN THE BODY. SOMETHING

4832
03:33:13,120 --> 03:33:17,720
LIKE NOR PLANT IMPLANT

4833
03:33:17,720 --> 03:33:19,840
SUBCUTANEAIOUSLY DELIVERS, BIRTH

4834
03:33:19,840 --> 03:33:21,560
CONTROL HORMONES OVER PERIOD OF

4835
03:33:21,560 --> 03:33:26,360
COUPLE OF YEARS WE FOLLOWED THAT

4836
03:33:26,360 --> 03:33:30,000
NOW DEVELOPED FLEXIBLE HYDRO GEL

4837
03:33:30,000 --> 03:33:31,880
RODS THAT CAN BE INJECTED

4838
03:33:31,880 --> 03:33:34,120
WITHOUT SURGERY SUBCUTANEOUSLY

4839
03:33:34,120 --> 03:33:35,680
AS A TRANSLATIONAL APPROACH. FOR

4840
03:33:35,680 --> 03:33:37,120
A CELL POPULATION, WE ARE

4841
03:33:37,120 --> 03:33:39,320
THINKING WE ARE GOING TO HAVE A

4842
03:33:39,320 --> 03:33:42,520
REPROGRAMMED ALLOGENEIC MASTER

4843
03:33:42,520 --> 03:33:45,040
CELL WE ARE GOING TO USE BECAUSE

4844
03:33:45,040 --> 03:33:46,400
IT WOULD BE WAY TOO EXPENSIVE TO

4845
03:33:46,400 --> 03:33:49,240
TRY TO DO THESE EDITS AND

4846
03:33:49,240 --> 03:33:51,760
TESTING ON PERSONALIZED IPSCs

4847
03:33:51,760 --> 03:33:54,440
TO CREATE IPSC TO REPROGRAM IT,

4848
03:33:54,440 --> 03:33:56,080
TEST IT, QUALITY CONTROL,

4849
03:33:56,080 --> 03:33:59,200
TALKING MILLIONS OF DOLLARS PER

4850
03:33:59,200 --> 03:34:03,400
IMPLANT VERSUS BANK OF SHELF

4851
03:34:03,400 --> 03:34:04,840
IMPLANTS. SO A WE HAVE TO SCALE

4852
03:34:04,840 --> 03:34:06,920
UP TO MID SIZE ANIMALS AND MAKES

4853
03:34:06,920 --> 03:34:08,520
SURE IT WORKS AND THEN HOPEFULLY

4854
03:34:08,520 --> 03:34:10,920
OVER THE NEXT DECADE TO CLINICAL

4855
03:34:10,920 --> 03:34:18,360
STUDIES. 

4856
03:34:18,360 --> 03:34:20,120
>>SCOTT HAS HIS HAND UP
SO WE

4857
03:34:20,120 --> 03:34:22,360
WILL GO TO SCOTT AND THEN A FEW

4858
03:34:22,360 --> 03:34:28,960
OTHERS. 

4859
03:34:28,960 --> 03:34:30,600
>>FARSHID BRINGS UP AN

4860
03:34:30,600 --> 03:34:31,960
IMPORTANT POINT, AFFECT

4861
03:34:31,960 --> 03:34:33,080
MECHANICAL LOAD ON CELLS.  ALL

4862
03:34:33,080 --> 03:34:34,840
THE TUCK ABOUT BIOLOGY AND THIS

4863
03:34:34,840 --> 03:34:38,160
MACROPHAGE AND THAT AND THIS

4864
03:34:38,160 --> 03:34:39,040
CYTOKINE BUT THE WHOLE OTHER

4865
03:34:39,040 --> 03:34:40,920
PART OF THE EQUATION, THIS IS

4866
03:34:40,920 --> 03:34:43,680
NOT LIVER OR PANCREAS. SO THANKS

4867
03:34:43,680 --> 03:34:48,040
FOR JUST POINTING OUT THAT

4868
03:34:48,040 --> 03:34:50,920
CRITICAL IMPORTANT, ALL STUDIES

4869
03:34:50,920 --> 03:34:51,840
IN BIOLOGY OF CELLS.

4870
03:34:51,840 --> 03:34:53,960
>>NOT JUST AS A LOAD
BEARING

4871
03:34:53,960 --> 03:34:55,840
TISSUE, IT HAS TO WITHSTAND TEN

4872
03:34:55,840 --> 03:34:57,840
TIMES YOUR BODY WEIGHT BUT ALSO

4873
03:34:57,840 --> 03:35:02,240
CAN WE USE AS A SIGNAL TO DRIVE

4874
03:35:02,240 --> 03:35:04,640
WHATEVER OUTPUT WE WANT. FOR

4875
03:35:04,640 --> 03:35:08,920
EXAMPLE WE BUILT GENE CIRCUITS

4876
03:35:08,920 --> 03:35:09,680
THAT DELIVER APT PAIN COMPOUNDS

4877
03:35:09,680 --> 03:35:11,760
IN RESPONSE TO LOADING AND DO IT

4878
03:35:11,760 --> 03:35:13,680
DIFFERENT MAGNITUDES OF LOADING 

4879
03:35:13,680 --> 03:35:16,080
ACTIVATION OF CERTAIN ION

4880
03:35:16,080 --> 03:35:18,120
CHANNEL VERSUS HIGHER THRESHOLD

4881
03:35:18,120 --> 03:35:21,200
ION CHANNEL. WE CAN TUNE ION

4882
03:35:21,200 --> 03:35:22,640
CHANNELS DOWN BY MUTATING THEM

4883
03:35:22,640 --> 03:35:24,960
AND CHANGING ON OFF DYNAMICS. SO

4884
03:35:24,960 --> 03:35:27,400
THERE IS A LOT OF FLEXIBILITY

4885
03:35:27,400 --> 03:35:29,040
BUT BECAUSE THERE IS FLEXIBILITY

4886
03:35:29,040 --> 03:35:29,840
A LOT OF QUESTIONS TO BE

4887
03:35:29,840 --> 03:35:38,040
ANSWERED.  AMBIKA.

4888
03:35:38,040 --> 03:35:39,880
>>HI, FARSHID, THANK YOU
FOR

4889
03:35:39,880 --> 03:35:45,200
GREAT TALK, EXCITING WORK. 

4890
03:35:45,200 --> 03:35:49,160
GENETIC REPROGRAMMING YOU DO IN

4891
03:35:49,160 --> 03:35:51,360
THESE CELLS, DO YOU KNOW TIMED

4892
03:35:51,360 --> 03:35:53,560
RESPONSE IS THIS A APLASTIC

4893
03:35:53,560 --> 03:35:54,720
EFFECT? HOW LONG DOES THE

4894
03:35:54,720 --> 03:35:56,480
RESPONSE STAY? AS WE DELIVER

4895
03:35:56,480 --> 03:35:59,240
THESE REPROGRAM CELLS, WHAT

4896
03:35:59,240 --> 03:36:01,000
HAPPENS TO SURROUNDING CELLS, DO

4897
03:36:01,000 --> 03:36:02,840
YOU EXPECT THEM TO CHANGE IN

4898
03:36:02,840 --> 03:36:05,400
ANYWAY?

4899
03:36:05,400 --> 03:36:07,080
>>GREAT QUESTION,
REPROGRAMMING

4900
03:36:07,080 --> 03:36:13,680
IS DONE BY CRISPER EDITING IN

4901
03:36:13,680 --> 03:36:15,280
IPSCs, WE IDENTIFY SINGLE CELL

4902
03:36:15,280 --> 03:36:17,840
WITH EDITS DONE PROPERLY WITHOUT

4903
03:36:17,840 --> 03:36:20,520
OFF TARGET EFFECTS. WHICH WE CAN

4904
03:36:20,520 --> 03:36:22,520
SEQUENCE AND THEN CLONE THAT ONE

4905
03:36:22,520 --> 03:36:24,320
SINGLE CELL. SO A RELATIVELY NOT

4906
03:36:24,320 --> 03:36:25,400
COMPLETELY BUT RELATIVELY

4907
03:36:25,400 --> 03:36:28,360
UNIFORM POPULATION. BECAUSE EVEN

4908
03:36:28,360 --> 03:36:29,560
CLONED CELLS COME FROM SINGLE

4909
03:36:29,560 --> 03:36:32,880
CELL ANALYSIS ARE NOT UNIFORM.

4910
03:36:32,880 --> 03:36:34,960
SO THAT IS THE CELL, THE EDITS

4911
03:36:34,960 --> 03:36:37,200
CANNOT TRANSFER TO ANY NEARBY

4912
03:36:37,200 --> 03:36:40,040
CELLS BUT WHAT WE FOUND IN

4913
03:36:40,040 --> 03:36:41,600
CO-CULTURE, THESE CELLS WILL

4914
03:36:41,600 --> 03:36:44,760
PROTECT OTHER CELLS AROUND THEM

4915
03:36:44,760 --> 03:36:47,120
FROM THE CYTOKINE EFFECT. I

4916
03:36:47,120 --> 03:36:48,560
DIDN'T SHOW IN VITRO DATA

4917
03:36:48,560 --> 03:36:50,440
BECAUSE IT WAS PUBLISHED A FEW

4918
03:36:50,440 --> 03:36:52,440
YEARS AGO BUT A SMALL NUMBER OF

4919
03:36:52,440 --> 03:36:55,320
EDITED CELLS PROTECT LARGE

4920
03:36:55,320 --> 03:36:56,120
NUMBER OF NATIVE CELLS.

4921
03:36:56,120 --> 03:36:58,000
>>WHAT IS THE LIFETIME OF
THESE

4922
03:36:58,000 --> 03:37:01,520
EDITED CELLS?

4923
03:37:01,520 --> 03:37:03,960
>>AS I MENTIONED TO DR.
CHU WE

4924
03:37:03,960 --> 03:37:05,840
HAD THEM SIX MONTHS SO FAR, THAT

4925
03:37:05,840 --> 03:37:09,040
IS LONGEST AND WE ARE -- THEY

4926
03:37:09,040 --> 03:37:11,200
ARE ACTIVATABLE AT SIX MONTHS IN

4927
03:37:11,200 --> 03:37:14,000
THE BODY SUB Q. IF WE INJECT AND

4928
03:37:14,000 --> 03:37:15,240
DON'T FORM IMPLANT THEY HAVE A

4929
03:37:15,240 --> 03:37:19,280
LIFE OF TWO DAYS.  THEN THEY ARE

4930
03:37:19,280 --> 03:37:22,240
CLEARED AND GONE. WE MANAGE TO

4931
03:37:22,240 --> 03:37:23,280
DIFFERENTIATE SOMETHING TO

4932
03:37:23,280 --> 03:37:24,040
MACROPHAGES THAT WILL STICK

4933
03:37:24,040 --> 03:37:25,360
AROUND FOR A FEW WEEKS BUT THAT

4934
03:37:25,360 --> 03:37:27,240
IS WHAT THE CELL INJECTION,

4935
03:37:27,240 --> 03:37:28,520
WHEREAS THE IMPLANT IS MONTHS OR

4936
03:37:28,520 --> 03:37:31,520
LONGER.

4937
03:37:31,520 --> 03:37:32,560
>>THANK YOU.

4938
03:37:32,560 --> 03:37:34,800
>>GEORGE MUSCHLER.

4939
03:37:34,800 --> 03:37:39,400
>>I HAVE BEEN FASCINATED
BY

4940
03:37:39,400 --> 03:37:41,400
YOUR WORK FOR A LONG TIME, AND

4941
03:37:41,400 --> 03:37:45,080
CHALLENGE NOT ONLY OF HAVING A

4942
03:37:45,080 --> 03:37:48,200
VERY SPECIFIC DRUG BUT ALSO

4943
03:37:48,200 --> 03:37:53,800
TIMING AND DURABILITY DELIVERY. 

4944
03:37:53,800 --> 03:37:55,560
MY QUESTION, THERE'S TWO

4945
03:37:55,560 --> 03:37:57,080
QUESTIONS, YOUR STRATEGY TAKING

4946
03:37:57,080 --> 03:37:59,040
IPS CELLS AND USING THAT AS YOUR

4947
03:37:59,040 --> 03:38:02,880
PLATFORM ON WHICH TO BUILD

4948
03:38:02,880 --> 03:38:04,000
STABLE CELL THERAPY, THAT GIVES

4949
03:38:04,000 --> 03:38:05,320
YOU THE OPPORTUNITY TO ROUND OUT

4950
03:38:05,320 --> 03:38:08,560
A LOT OF VARIABILITY TAKEN FROM

4951
03:38:08,560 --> 03:38:13,520
EITHER AUTOLOGOUS CELLS OR

4952
03:38:13,520 --> 03:38:15,400
DIFFERENT BATCHES OF MSCs FROM

4953
03:38:15,400 --> 03:38:17,200
THE SAME INDIVIDUAL. TWO

4954
03:38:17,200 --> 03:38:18,120
QUESTIONS THERE TECHNICALLY DO

4955
03:38:18,120 --> 03:38:23,480
YOU EXPECT TO NEED TO TAKE I P,S

4956
03:38:23,480 --> 03:38:26,280
CELLS THROUGH AN MSC TYPE

4957
03:38:26,280 --> 03:38:28,400
PHENOTYPE ON WAY TO BECOMING

4958
03:38:28,400 --> 03:38:31,280
THERAPY? OR DO YOU CARE? WHETHER

4959
03:38:31,280 --> 03:38:34,840
THEY GO THROUGH PARTICULAR MSC

4960
03:38:34,840 --> 03:38:37,520
PHENOTYPE. RELATED TO THAT WHERE

4961
03:38:37,520 --> 03:38:39,200
WOULD YOU LIKE TO DELIVER THESE

4962
03:38:39,200 --> 03:38:42,200
CELLS, CAN YOU FEEL NEED TO MAKE

4963
03:38:42,200 --> 03:38:43,680
CARTILAGE CELLS THAT DELIVER

4964
03:38:43,680 --> 03:38:45,760
DRUGS OR BE HAPPY WITH A CELL

4965
03:38:45,760 --> 03:38:49,400
THAT REMAINS DURABLY RESISTANT

4966
03:38:49,400 --> 03:38:50,320
AND SYNOVIAL?

4967
03:38:50,320 --> 03:38:52,800
>>WE DO GO THROUGH, I
DON'T

4968
03:38:52,800 --> 03:38:54,760
CALL IT MSC STATE BUT WE GO

4969
03:38:54,760 --> 03:38:56,720
THROUGH A STEP WISE

4970
03:38:56,720 --> 03:38:57,600
DIFFERENTIATION PROTOCOL THAT

4971
03:38:57,600 --> 03:38:59,280
ONE OF MY POST DOCS DEVELOPED

4972
03:38:59,280 --> 03:39:01,920
WHICH BASICALLY RECREATES THE

4973
03:39:01,920 --> 03:39:04,240
STEPS DURING EMBRYO GENESIS OF

4974
03:39:04,240 --> 03:39:06,120
CARTILAGE. SO 12 DAY CULTURE WE

4975
03:39:06,120 --> 03:39:10,160
HAVE TO CHANGE MASSIVE NUMBERS

4976
03:39:10,160 --> 03:39:12,320
OF GROWTH FACTORS DURING THOSE

4977
03:39:12,320 --> 03:39:17,640
12 DAYS. THEY ARE IN THAT

4978
03:39:17,640 --> 03:39:18,880
CHONDROGENNIC PHASE AND FORM

4979
03:39:18,880 --> 03:39:21,080
CARTILAGE. WE WANT CARTILAGE SO

4980
03:39:21,080 --> 03:39:22,760
WE DON'T NECESSARY -- THE MOUSE

4981
03:39:22,760 --> 03:39:26,960
CELLS EASIER, THEY GO THROUGH

4982
03:39:26,960 --> 03:39:30,440
EARLY MICROMASS PHASE WITH AND

4983
03:39:30,440 --> 03:39:32,240
AFTER THAT MESENCHYMAL AND

4984
03:39:32,240 --> 03:39:34,760
TURNED TO CARTILAGE. WE WANT

4985
03:39:34,760 --> 03:39:38,520
THEM TO FORM STABLE CARTILAGE.

4986
03:39:38,520 --> 03:39:40,160
AID NEEDS TO BE FUNCTIONAL

4987
03:39:40,160 --> 03:39:42,560
CARTILAGE, IF SUB Q IT NEEDS TO

4988
03:39:42,560 --> 03:39:44,760
ENCAPSULATE CELLS, TO PROTECT,

4989
03:39:44,760 --> 03:39:46,560
SURVIVE IN AVASCULAR ENVIRONMENT

4990
03:39:46,560 --> 03:39:49,560
AND PREVENT INVASION WHICH MOST

4991
03:39:49,560 --> 03:39:52,160
CARTILAGE TENDS TO DO THAT.

4992
03:39:52,160 --> 03:39:55,120
THESE ARE IPSCs SO WE CAN

4993
03:39:55,120 --> 03:39:58,600
DIFFERENTIATE TO NEURONS, INTO

4994
03:39:58,600 --> 03:39:59,720
FIBROBLASTIC TYPE CELLS, INTO

4995
03:39:59,720 --> 03:40:01,840
MUSCLE CELLS, IF THAT WERE

4996
03:40:01,840 --> 03:40:03,640
POTENTIAL AND WE HAVE DONE THIS

4997
03:40:03,640 --> 03:40:05,840
WITH SOME ANTI-FIBROTIC CELLS WE

4998
03:40:05,840 --> 03:40:08,920
DEVELOPED WITH IN COLLABORATION

4999
03:40:08,920 --> 03:40:11,040
WITH JOHNNY HUARD,

5000
03:40:11,040 --> 03:40:12,320
DIFFERENTIATED INTO MUSCLE AND

5001
03:40:12,320 --> 03:40:14,360
IMPLANTED IN MUSCLE TO PREVENT

5002
03:40:14,360 --> 03:40:16,720
MUSCLE FIBROSIS IN RESPONSE TO

5003
03:40:16,720 --> 03:40:19,880
TGF BETA. SO STEM PART GIVES YOU

5004
03:40:19,880 --> 03:40:21,960
FLEXIBILITY IN HOW YOU

5005
03:40:21,960 --> 03:40:24,040
DIFFERENTIATE IT BUT HOW WE GET

5006
03:40:24,040 --> 03:40:25,480
THERE FOR THIS WE CARE LESS,

5007
03:40:25,480 --> 03:40:26,400
MORE THE END PRODUCT THAT

5008
03:40:26,400 --> 03:40:28,480
MATTERS.

5009
03:40:28,480 --> 03:40:34,640
>>THANK YOU. HAND OFF TO
SCOTT

5010
03:40:34,640 --> 03:40:45,040
RODEO YOU ARE ON MUTE.

5011
03:40:48,240 --> 03:40:53,120
>>SORRY; I WAS THINKING
-- DR.

5012
03:40:53,120 --> 03:40:54,960
BARRY IS MANY THE TRANSLATIONAL

5013
03:40:54,960 --> 03:40:57,440
MEDICINE INSTITUTE AT COLORADO

5014
03:40:57,440 --> 03:40:58,760
STATE UNIVERSITY. ALSO PROFESSOR

5015
03:40:58,760 --> 03:41:01,640
CELLULAR THERAPY AFFILIATED WITH

5016
03:41:01,640 --> 03:41:03,880
REGENERATIVE MEDICINE AT THE

5017
03:41:03,880 --> 03:41:05,520
NATIONAL UNIVERSITY OF IRELAND,

5018
03:41:05,520 --> 03:41:07,360
DR. BARRY IS A MAJOR CONTRIBUTOR

5019
03:41:07,360 --> 03:41:09,080
TO THE FIELD OF TISSUE

5020
03:41:09,080 --> 03:41:10,320
ENGINEERING AND REGENERATIVE

5021
03:41:10,320 --> 03:41:11,560
MEDICINE. HIS WORK CONTRIBUTED

5022
03:41:11,560 --> 03:41:13,680
TO OUR CURRENT UNDERSTANDING OF

5023
03:41:13,680 --> 03:41:17,520
THE PHENOTYPIC ATTRIBUTES OF

5024
03:41:17,520 --> 03:41:20,800
MESENCHYMAL STROMAL CELLS,

5025
03:41:20,800 --> 03:41:22,200
IMPORTANTLY COMMITTED TO

5026
03:41:22,200 --> 03:41:23,720
DEVELOPMENT OF METHODS FOR

5027
03:41:23,720 --> 03:41:25,280
AUTOMATED SCALABLE CELL

5028
03:41:25,280 --> 03:41:27,000
EXPANSION FOR GMP APPLICATION

5029
03:41:27,000 --> 03:41:28,480
AND THAT WORK COORDINATED

5030
03:41:28,480 --> 03:41:32,000
CLINICAL TRIALS TO TEST EFFICACY

5031
03:41:32,000 --> 03:41:34,400
OF STROMAL CELL DELIVERY AND

5032
03:41:34,400 --> 03:41:37,200
REGENERATIVE ARTHRITIS AND

5033
03:41:37,200 --> 03:41:39,640
RECIPIENT OF THE MARSHALL AWARD

5034
03:41:39,640 --> 03:41:41,240
FOR EXCELLENCE FROM THE ORS.

5035
03:41:41,240 --> 03:41:43,280
ALSO ELECTED MEMBER OF THE ROYAL

5036
03:41:43,280 --> 03:41:44,960
IRISH ACADEMY LAST YEAR SO

5037
03:41:44,960 --> 03:41:47,640
WELCOME, WE WILL HEAR TALK ON

5038
03:41:47,640 --> 03:41:50,280
MSC THERAPY FOR OSTEOARTHRITIS. 

5039
03:41:50,280 --> 03:41:51,440
>>THANK YOU VERY MUCH,
DR.

5040
03:41:51,440 --> 03:41:52,440
RODEO FOR THAT NICE

5041
03:41:52,440 --> 03:41:54,920
INTRODUCTION. I HAVE TO SAY THIS

5042
03:41:54,920 --> 03:41:57,520
ENTIRE DISCUSSION HAS BEEN

5043
03:41:57,520 --> 03:41:59,760
FASCINATING AND INFORMATIVE.

5044
03:41:59,760 --> 03:42:02,520
VERY PRIVILEGED TO CONTRIBUTE.

5045
03:42:02,520 --> 03:42:04,320
THE REQUEST WAS TO TALK ABOUT

5046
03:42:04,320 --> 03:42:06,200
LIMITATIONS AND CHALLENGES IN

5047
03:42:06,200 --> 03:42:08,000
CLINICAL USE OF BIOLOGICS BUT

5048
03:42:08,000 --> 03:42:10,280
GOING TO FOCUS ON -- MY

5049
03:42:10,280 --> 03:42:11,960
DISCUSSION ON MSC BECAUSE THIS

5050
03:42:11,960 --> 03:42:19,880
IS TOPIC THAT I KNOW MOST ABOUT 

5051
03:42:19,880 --> 03:42:22,760
WAITING FOR SLIDES TO ADVANCE.

5052
03:42:22,760 --> 03:42:25,480
MOVE TO NEXT SLIDE PLEASE

5053
03:42:25,480 --> 03:42:26,800
BECAUSE THESE ARE CONFLICTS TO

5054
03:42:26,800 --> 03:42:28,080
MENTION AT THE BEGINNING OF THE

5055
03:42:28,080 --> 03:42:32,360
TALK, NEXT SLIDE PLEASE.  I WANT

5056
03:42:32,360 --> 03:42:34,960
TO TALK ABOUT FOR FOUR TOPICS.

5057
03:42:34,960 --> 03:42:36,720
ONE WHERE WE ARE IN TERMS OF

5058
03:42:36,720 --> 03:42:38,240
CLINICAL ASSESSMENT OF MSC

5059
03:42:38,240 --> 03:42:40,160
THERAPY FOR TREATMENT OF

5060
03:42:40,160 --> 03:42:41,400
OSTEOARTHRITIS, WHAT HAS AND

5061
03:42:41,400 --> 03:42:43,200
NEEDS TO BE DONE. SECONDLY

5062
03:42:43,200 --> 03:42:45,800
TECHNICAL STRATEGIES

5063
03:42:45,800 --> 03:42:46,760
PARTICULARLY AROUND PRODUCTION

5064
03:42:46,760 --> 03:42:50,320
OF THE CELL PRODUCT PROBLEMS WE

5065
03:42:50,320 --> 03:42:53,280
ARE AWARE OF THERE. THIRDLY,

5066
03:42:53,280 --> 03:42:54,200
WHAT WE UNDERSTAND ABOUT

5067
03:42:54,200 --> 03:42:57,440
MECHANISM OF ACTION OF CELLS TO

5068
03:42:57,440 --> 03:42:59,960
DELIVER TO THE JOINT AND FINALLY

5069
03:42:59,960 --> 03:43:01,720
SOME IDEA WAY FORWARD, WHAT WE

5070
03:43:01,720 --> 03:43:04,360
NEED TO DO IN TERMS OF ADVANCING

5071
03:43:04,360 --> 03:43:09,200
THE FIELD FORWARD. SO FIRST A

5072
03:43:09,200 --> 03:43:11,160
QUICK SUMMARY OF WHAT WE HAVE

5073
03:43:11,160 --> 03:43:12,640
BEEN DOING IN TERMS OF CLINICAL

5074
03:43:12,640 --> 03:43:15,320
ASSESSMENT OF UTILITY OF MSC

5075
03:43:15,320 --> 03:43:17,760
TREATMENT IN OSTEOARTHRITIS.  SO

5076
03:43:17,760 --> 03:43:19,120
THE CONTROL IS NOT WORKING FOR

5077
03:43:19,120 --> 03:43:22,080
ME, SO I WILL ASK YOU PLEASE TO

5078
03:43:22,080 --> 03:43:23,440
KEEP ADVANCING. THIS IS THE

5079
03:43:23,440 --> 03:43:24,640
CLINICAL PATHWAY, CLINICAL

5080
03:43:24,640 --> 03:43:26,240
TRIALS PATHWAY THAT WE NEED TO

5081
03:43:26,240 --> 03:43:28,880
FOLLOW WHEN WE ARE LOOKING AT

5082
03:43:28,880 --> 03:43:31,720
EXPANDED MSC TREATMENT FOR ANY

5083
03:43:31,720 --> 03:43:36,320
CONDITION, THE STANDARD PHASED

5084
03:43:36,320 --> 03:43:38,320
CLINICAL TRIAL PICTURE WHERE WE

5085
03:43:38,320 --> 03:43:40,280
GO THROUGH PHASE 1 TO PHASE 4

5086
03:43:40,280 --> 03:43:45,360
POST MARKETING ASSESSMENTS AND

5087
03:43:45,360 --> 03:43:46,920
SUBSEQUENT PHASE WE TREAT BIGGER

5088
03:43:46,920 --> 03:43:49,320
NUMBERS OF PATIENTS SO PHASE 2

5089
03:43:49,320 --> 03:43:52,600
STUDY THINKING ABOUT 100 TO 500

5090
03:43:52,600 --> 03:43:54,840
PATIENTS IN PHASE 3 STUDY

5091
03:43:54,840 --> 03:43:56,440
THINKING A LARGER NUMBER THAN

5092
03:43:56,440 --> 03:43:58,640
THAT IN ORDER TO BUILD BODY OF

5093
03:43:58,640 --> 03:43:59,600
EVIDENCE TO BE RELIABLE AND

5094
03:43:59,600 --> 03:44:03,080
CONVINCING.  THIS IS AN

5095
03:44:03,080 --> 03:44:07,320
INTERESTING PAPER PUBLISHED JUST

5096
03:44:07,320 --> 03:44:08,280
RECENTLY I BY (INAUDIBLE) WHICH

5097
03:44:08,280 --> 03:44:13,560
IS ANALYSIS OF THE STATUS OF

5098
03:44:13,560 --> 03:44:14,800
CLINICAL TRIALS, UTILIZING

5099
03:44:14,800 --> 03:44:18,040
CULTURE EXPANDED MSC FOR WHOLE

5100
03:44:18,040 --> 03:44:21,240
VARIETY OF DIFFERENT INDICATIONS

5101
03:44:21,240 --> 03:44:23,000
LOOKS OVER MULTIPLE YEAR PERIOD

5102
03:44:23,000 --> 03:44:25,280
YOU CAN SEE HERE THE PHASE 1

5103
03:44:25,280 --> 03:44:27,520
STUDIES IN BLUE, PHASE 2 ORANGE

5104
03:44:27,520 --> 03:44:29,840
FADES 3 IN GRAY. WHAT IS

5105
03:44:29,840 --> 03:44:32,160
STRIKING ABOUT THIS PICTURE IS

5106
03:44:32,160 --> 03:44:34,440
THE LACK OF PROGRESSION TO PHASE

5107
03:44:34,440 --> 03:44:36,720
3 STUDY SO THERE'S MULTIPLE

5108
03:44:36,720 --> 03:44:39,640
PHASE 1 TRIAL IN FACT HUNDREDS

5109
03:44:39,640 --> 03:44:43,400
OF THEM, PHASE 2 TRIALS BUT

5110
03:44:43,400 --> 03:44:44,800
LIMITED PROGRESSION BEYOND PHASE

5111
03:44:44,800 --> 03:44:50,720
2 TO PHASE 3. TRUE FOR EVERY

5112
03:44:50,720 --> 03:44:52,560
TARGET INDICATION. SO RESULTS OF

5113
03:44:52,560 --> 03:44:55,080
EARLY TRIALS ARE NOT GOOD ENOUGH

5114
03:44:55,080 --> 03:44:56,440
OR DESIGN GOOD ENOUGH BECAUSE

5115
03:44:56,440 --> 03:44:59,440
THE PROGRESSION TOPAZ 3 IS

5116
03:44:59,440 --> 03:45:03,760
LIMITED. SO THERE IS A PIPELINE

5117
03:45:03,760 --> 03:45:08,000
BUT THAT PRION IS NOT

5118
03:45:08,000 --> 03:45:10,600
PROGRESSING. I HAD A QUICK LOOK

5119
03:45:10,600 --> 03:45:11,920
AT THE CURRENT CLINICAL TRIAL

5120
03:45:11,920 --> 03:45:15,000
REGISTRY IN THE CONTEXT OF MSC

5121
03:45:15,000 --> 03:45:16,920
TRIALS FOR OSTEOARTHRITIS. ABOUT

5122
03:45:16,920 --> 03:45:19,200
120 OR SO TRIALS LISTED LOOKING

5123
03:45:19,200 --> 03:45:22,560
AT MSC TREATMENT FOR OA. ABOUT

5124
03:45:22,560 --> 03:45:27,080
50 ARE PHASE 1, 60 PHASE 2 AND

5125
03:45:27,080 --> 03:45:29,000
HANDFUL ARE PHASE 3. LOOK AT

5126
03:45:29,000 --> 03:45:31,520
PHASE 3 TRIAL ON THE REGISTRY,

5127
03:45:31,520 --> 03:45:35,200
SIX OF THOSE ARE REPORTED BEING

5128
03:45:35,200 --> 03:45:39,280
COMPLETED THE REST RECRUITING OR

5129
03:45:39,280 --> 03:45:41,240
AMONG STATUS OR NOT STARTTH

5130
03:45:41,240 --> 03:45:44,320
STARTED. ONE IS NOT RELEVANT TO

5131
03:45:44,320 --> 03:45:50,960
MSC, BIGGEST IS THE MILE STUDY,

5132
03:45:50,960 --> 03:45:51,720
WHICH IS COMPLETE BUT RESULTS

5133
03:45:51,720 --> 03:45:54,960
NOT POSTED AS I UNDERSTAND IT. 

5134
03:45:54,960 --> 03:45:58,240
THE OTHER PHASE 3 STUDY LISTED

5135
03:45:58,240 --> 03:46:00,000
ARE RATHER SMALL AND IT IS HARD

5136
03:46:00,000 --> 03:46:02,800
TO UNDERSTAND IF THEY REALLY ARE

5137
03:46:02,800 --> 03:46:04,360
JUSTIFIABLY REFERRED TO AS PHASE

5138
03:46:04,360 --> 03:46:06,120
3 TRIALS WHEN THEY REPRESENT THE

5139
03:46:06,120 --> 03:46:09,040
BODY OF EVIDENCE WE NEED TO HAVE

5140
03:46:09,040 --> 03:46:11,720
TO ANSWER THE QUESTION

5141
03:46:11,720 --> 03:46:12,520
CONVINCINGLY WHETHER THIS

5142
03:46:12,520 --> 03:46:15,480
TREATMENT WORKS OR NOT.  SO WE

5143
03:46:15,480 --> 03:46:17,840
HAVE BEEN DOING CLINICAL STUDIES

5144
03:46:17,840 --> 03:46:19,720
IN EUROPE VERY QUICKLY SUMMARIZE

5145
03:46:19,720 --> 03:46:21,840
WHERE WE ARE WITH THIS. WE

5146
03:46:21,840 --> 03:46:23,600
CARRIED OUT PHASE 1 STUDY WHICH

5147
03:46:23,600 --> 03:46:24,480
COMPLETED HOE WHICH WAS

5148
03:46:24,480 --> 03:46:27,240
COMPLETED IN 2015 OR 16. LOOKING

5149
03:46:27,240 --> 03:46:30,880
AT AUTOLOGOUS EXPANDED ADIPOSE

5150
03:46:30,880 --> 03:46:33,840
DERIVED CELLS FOR TREATMENT OF

5151
03:46:33,840 --> 03:46:35,600
MODERATE TO SEVERE

5152
03:46:35,600 --> 03:46:37,000
OSTEOARTHRITIS OF THE KNEE. SO

5153
03:46:37,000 --> 03:46:40,840
VERY SIMPLE PROTOCOL, PATIENTS

5154
03:46:40,840 --> 03:46:42,080
INFER STRONG VASCULAR FRACTION

5155
03:46:42,080 --> 03:46:44,640
IS REPAIRED, CELLS ISOLATED

5156
03:46:44,640 --> 03:46:47,560
EXPANDED FROM SPF AND AT THE END

5157
03:46:47,560 --> 03:46:49,120
OF PASSAGE 2 CELLS ARE DELIVERED

5158
03:46:49,120 --> 03:46:53,520
BACK TO THE KNEE JOINT OF THE

5159
03:46:53,520 --> 03:46:56,400
PATIENT, IN THIS PHASE 1 STUDY

5160
03:46:56,400 --> 03:46:58,880
WE TREATED 18 PATIENTS AND THREE

5161
03:46:58,880 --> 03:47:02,440
COHORT, LOW MEDIUM AND HIGH DOSE

5162
03:47:02,440 --> 03:47:06,720
AND THEN IN THE NEXT SLIDE,

5163
03:47:06,720 --> 03:47:09,080
INCLUSION EXCLUSION CRITERIA ARE

5164
03:47:09,080 --> 03:47:11,320
SUMMARIZED HERE OBVIOUSLY A VERY

5165
03:47:11,320 --> 03:47:12,640
COMPREHENSIVE LIST OF INCLUSION

5166
03:47:12,640 --> 03:47:15,320
AN EXCLUSION CRITERIA, I'M

5167
03:47:15,320 --> 03:47:17,000
SUMMARIZING THE CRITICAL POINTS,

5168
03:47:17,000 --> 03:47:19,280
THOSE PATIENTS HAD SYMPTOMATIC

5169
03:47:19,280 --> 03:47:20,640
PRIMARY OSTEOARTHRITIS OF THE

5170
03:47:20,640 --> 03:47:24,960
KNEE, AT LEAST KL 2 OR 3, 50 TO

5171
03:47:24,960 --> 03:47:27,760
# 0 YEARS OLD, WITHOUT ANY

5172
03:47:27,760 --> 03:47:29,600
SECONDARY OSTEOARTHRITIS OR

5173
03:47:29,600 --> 03:47:31,840
EVIDENCE OF OA OR OTHER

5174
03:47:31,840 --> 03:47:37,120
CONDITIONS. NEXT SLIDE.  THE

5175
03:47:37,120 --> 03:47:39,960
STUDY WAS SIX PATIENTS PER GROUP

5176
03:47:39,960 --> 03:47:42,320
NOT STATISTICAL SIGNIFICANCE.

5177
03:47:42,320 --> 03:47:43,640
THE OTHER SYMPTOM MODIFYING ONLY

5178
03:47:43,640 --> 03:47:45,800
THERE WAS NO ATTEMPT MADE TO

5179
03:47:45,800 --> 03:47:48,640
LOOK FOR DISEASE MODIFIED

5180
03:47:48,640 --> 03:47:50,680
OUTCOME. BASED ON SMALL STUDY

5181
03:47:50,680 --> 03:47:51,840
THERE WAS INTERESTING

5182
03:47:51,840 --> 03:47:53,000
OBSERVATION, SIGNIFICANT

5183
03:47:53,000 --> 03:47:54,240
REDUCTION IN PAIN SCORES IN ALL

5184
03:47:54,240 --> 03:47:57,560
THE PATIENTS WITHIN 24 HOURS OF

5185
03:47:57,560 --> 03:47:58,560
RECEIVING THE TREATMENT. THE

5186
03:47:58,560 --> 03:48:01,120
NEXT SLIDE A SIGNIFICANT

5187
03:48:01,120 --> 03:48:03,720
INTRODUCTION IN THE WOMAK SCORE

5188
03:48:03,720 --> 03:48:05,320
IN THE PATIENT THAT RECEIVED THE

5189
03:48:05,320 --> 03:48:07,920
SUB TREATMENT. THE OTHER

5190
03:48:07,920 --> 03:48:08,960
INTEREST OBSERVATION THERE WAS

5191
03:48:08,960 --> 03:48:10,320
IMPROVEMENT IN SYMPTOMS BUT

5192
03:48:10,320 --> 03:48:12,160
MOSTLY THE LOWEST CELL DOSE

5193
03:48:12,160 --> 03:48:13,640
WHICH GAVE RISE RISE TO BEST

5194
03:48:13,640 --> 03:48:16,320
RESPONSE IN THESE PATIENTS. SO

5195
03:48:16,320 --> 03:48:17,760
BASED ON THESE OBSERVATIONS AND

5196
03:48:17,760 --> 03:48:19,720
THE STUDY WAS ENTIRELY SAFE WITH

5197
03:48:19,720 --> 03:48:22,400
NO ADVERSE EVENTS REPORTED, WE

5198
03:48:22,400 --> 03:48:28,200
WENT TO PHASE 2B STUDY. THIS IS

5199
03:48:28,200 --> 03:48:30,400
DESIGNED AS MULTI-CENTER PLACEBO

5200
03:48:30,400 --> 03:48:32,760
CONTROLLED FULLY RANDOMIZED

5201
03:48:32,760 --> 03:48:34,920
CLINICAL TRIAL TO ASSESS

5202
03:48:34,920 --> 03:48:37,200
AUTOLOGOUS EXPANDED ARC

5203
03:48:37,200 --> 03:48:39,920
TREATMENT IN MICE MODERATE TO

5204
03:48:39,920 --> 03:48:40,840
SEVERE OSTEOARTHRITIS AND THIS

5205
03:48:40,840 --> 03:48:42,480
STUDY HAS JUST COMPLETED, IT WAS

5206
03:48:42,480 --> 03:48:45,560
SEVERELY IMPACTED BY COVID AND

5207
03:48:45,560 --> 03:48:48,240
WAS BADLY DELAYED AS A RESULT OF

5208
03:48:48,240 --> 03:48:50,440
COVID SO WE DIDN'T REACH THE END

5209
03:48:50,440 --> 03:48:52,280
POINT OF 153 PATIENTS THAT WE

5210
03:48:52,280 --> 03:48:54,640
INTENDED TO. NONETHELESS STUDY

5211
03:48:54,640 --> 03:48:57,520
IS FINISHED AND THE PRIMARY

5212
03:48:57,520 --> 03:48:59,720
CLINICAL OUTCOME WILL BE

5213
03:48:59,720 --> 03:49:03,640
AVAILABLE IN A MONTH'S TIME. THE

5214
03:49:03,640 --> 03:49:07,720
DESIGN OF THE STUDY IS HOPEFULLY

5215
03:49:07,720 --> 03:49:08,680
SUFFICIENT TO UNDERSTAND WHETHER

5216
03:49:08,680 --> 03:49:10,720
THERE IS A STRUCTURE OR DISEASE

5217
03:49:10,720 --> 03:49:12,160
MODIFYING AFFECT ASSOCIATED WITH

5218
03:49:12,160 --> 03:49:13,840
THE TREATMENT OPPOSED TO MERELY

5219
03:49:13,840 --> 03:49:16,960
SYMPTOM MODIFYING EFFECT. SO ALL

5220
03:49:16,960 --> 03:49:18,800
TOGETHER PATIENTS COME FOR NINE

5221
03:49:18,800 --> 03:49:22,160
VISITS, THE FIRST TWO ARE FOR

5222
03:49:22,160 --> 03:49:24,640
SCREENING AND ENROLLMENT. AND

5223
03:49:24,640 --> 03:49:26,560
FOR COLLECTION OF THE ADIPOSE

5224
03:49:26,560 --> 03:49:29,040
TISSUE. THIRD IS FOR TREATMENT

5225
03:49:29,040 --> 03:49:31,040
WITH CELLS AND THEN ALL

5226
03:49:31,040 --> 03:49:34,480
SUBSEQUENT VISITS UP TO 24

5227
03:49:34,480 --> 03:49:36,280
MONTHS ARE FOR RADIOLOGY,

5228
03:49:36,280 --> 03:49:37,480
CLINICAL ASSESSMENT RADIOLOGY

5229
03:49:37,480 --> 03:49:41,000
AND MRI. HOPEFULLY WHEN THESE

5230
03:49:41,000 --> 03:49:42,560
DATA ARE COMPLETED WE WILL HAVE

5231
03:49:42,560 --> 03:49:44,320
A GOOD IDEA WHETHER THERE IS A

5232
03:49:44,320 --> 03:49:46,080
TISSUE RESPONSE OR REGENERATIVE

5233
03:49:46,080 --> 03:49:49,000
RESPONSE ASSOCIATED WITH CELL

5234
03:49:49,000 --> 03:49:50,880
TREATMENT. AND IF THE RESULTS OF

5235
03:49:50,880 --> 03:49:54,200
THIS, SIGNAL WE SEE MONTHS'S

5236
03:49:54,200 --> 03:49:56,280
TIME WHEN WE -- WHEN SIX MONTH

5237
03:49:56,280 --> 03:49:57,520
TIME POINT POST TREATMENT IS

5238
03:49:57,520 --> 03:49:58,520
REACHED THEN WE WILL START

5239
03:49:58,520 --> 03:50:01,480
PLANNING FOR A PHASE 3 LARGE

5240
03:50:01,480 --> 03:50:03,160
STUDY. WE ALSO SWITCH FROM

5241
03:50:03,160 --> 03:50:04,480
AUTOLOGOUS TO ALLOGENEIC

5242
03:50:04,480 --> 03:50:06,520
TREATMENT BECAUSE THE LO LISTICS

5243
03:50:06,520 --> 03:50:08,440
AND PRACTICALITY OF DOING

5244
03:50:08,440 --> 03:50:10,240
AUTOLOGOUS EXPANDED CELL THERAPY

5245
03:50:10,240 --> 03:50:14,680
IN LARGE GROUP IS TOO DIFFICULT.

5246
03:50:14,680 --> 03:50:16,520
THE IDEA WILL BE IF THINGS LOOK

5247
03:50:16,520 --> 03:50:18,720
GOOD TO MOVE TO PHASE 3

5248
03:50:18,720 --> 03:50:21,920
ALLOGENEIC STUDY WITH SOME

5249
03:50:21,920 --> 03:50:22,920
IMPROVEMENT AND MANUFACTURING

5250
03:50:22,920 --> 03:50:24,960
PROTOCOL BASED ON LESSONS

5251
03:50:24,960 --> 03:50:26,360
LEARNED FROM THE -- WHAT WE HAVE

5252
03:50:26,360 --> 03:50:31,120
DONE PREVIOUSLY. THE TECHNICAL

5253
03:50:31,120 --> 03:50:33,000
STRATEGY RELATING TO HOW DO YOU

5254
03:50:33,000 --> 03:50:35,240
PRODUCE THE CELLS IN THE HIGHLY

5255
03:50:35,240 --> 03:50:36,800
CONSISTENT REPRODUCIBLE AND HIGH

5256
03:50:36,800 --> 03:50:38,360
QUALITY FASHION TO USE IN STUDY

5257
03:50:38,360 --> 03:50:41,120
LIKE THIS AND ULTIMATELY TO USE

5258
03:50:41,120 --> 03:50:42,760
IN THE WIDE IRPATIENT

5259
03:50:42,760 --> 03:50:44,680
POPULATION.  SOMETHING WE HAVE

5260
03:50:44,680 --> 03:50:48,240
GIVEN GREAT DEAL OF THOUGHT TO

5261
03:50:48,240 --> 03:50:49,320
AND TO NEXT SLIDE PLEASE THIS

5262
03:50:49,320 --> 03:50:50,760
SHOW IT IS MANUFACTURING

5263
03:50:50,760 --> 03:50:52,320
PROTOCOL WE HAVE USED IN

5264
03:50:52,320 --> 03:50:53,280
PRACTICALLY EVERY GROUP THAT

5265
03:50:53,280 --> 03:50:58,280
PREPARES MSC FOR ANY PURPOSE USE

5266
03:50:58,280 --> 03:51:01,240
PROTOCOL BASICALLY. FROM THE

5267
03:51:01,240 --> 03:51:04,120
TISSUE, WE EXTRACT THE CELLS AND

5268
03:51:04,120 --> 03:51:06,320
EXPAND THE CELLS OVER SEVERAL

5269
03:51:06,320 --> 03:51:07,760
PASSAGES USING A MULTI-STEP

5270
03:51:07,760 --> 03:51:10,840
PROTOCOL SUCH AS WHAT YOU SEE

5271
03:51:10,840 --> 03:51:13,040
HERE, WE UTILIZE DIFFERENT

5272
03:51:13,040 --> 03:51:15,600
QUALITY CONTROL TESTS TO ASSURE

5273
03:51:15,600 --> 03:51:17,240
-- ASSESS THE QUALITY OF THE

5274
03:51:17,240 --> 03:51:20,200
CELLS AND MAKE SURE THAT THEY

5275
03:51:20,200 --> 03:51:23,920
ARE FREE OF ANY MICROBIAL

5276
03:51:23,920 --> 03:51:25,080
CONTAMINATION, SO ON. AT THE END

5277
03:51:25,080 --> 03:51:28,640
OF THE CELL EXPANSION PROTOCOL

5278
03:51:28,640 --> 03:51:33,400
WE USE THE ISCT STANDARD TESTING

5279
03:51:33,400 --> 03:51:34,960
METHODS TO -- BEFORE CELLS ARE

5280
03:51:34,960 --> 03:51:39,880
RELEASED. NEXT SLIDE PLEASE. 

5281
03:51:39,880 --> 03:51:41,880
THIS IS WHERE THINGS START TO

5282
03:51:41,880 --> 03:51:46,240
GET COMPLICATED AND WHAT WE ARE

5283
03:51:46,240 --> 03:51:47,960
TREADING ON THIN ICE BECAUSE

5284
03:51:47,960 --> 03:51:50,200
MENTIONED BY DR. ROBEY AND ONE

5285
03:51:50,200 --> 03:51:54,160
OF THE QUESTIONS SHE ADDRESSED

5286
03:51:54,160 --> 03:51:54,720
EARLIER THERE ARE DIFFERENT

5287
03:51:54,720 --> 03:51:55,200
DIFFERENCES PHENOTYPIC

5288
03:51:55,200 --> 03:51:56,800
DIFFERENCES DEPENDING WHERE THE

5289
03:51:56,800 --> 03:52:00,440
CELLS ARE ISOLATED FROM, DR.

5290
03:52:00,440 --> 03:52:02,760
GUILAK MENTIONED MSC PRESENCE

5291
03:52:02,760 --> 03:52:05,360
ARE A COMPLEX MIXTURE OF CELLS

5292
03:52:05,360 --> 03:52:07,320
TYPES. IT IS BORRIS THAN THAT.

5293
03:52:07,320 --> 03:52:10,600
BEKNOW NUMBER ONE, THE CULTURE

5294
03:52:10,600 --> 03:52:12,920
EXPANDED MSC HAS LITTLE

5295
03:52:12,920 --> 03:52:16,320
RELATIONSHIP TO IN VIVO CELL

5296
03:52:16,320 --> 03:52:18,640
PHENOTYPE. NUMBER TWO, A MIX IN

5297
03:52:18,640 --> 03:52:20,480
HETEROGENOUS POPULATION OF

5298
03:52:20,480 --> 03:52:24,920
CELLS, THE HETEROGENEITY AND

5299
03:52:24,920 --> 03:52:27,520
BIOLOGICAL PHENOTYPE IS REALLY

5300
03:52:27,520 --> 03:52:29,360
DEPENDENT ON THE CULTURE --

5301
03:52:29,360 --> 03:52:32,200
PHENOTYPE IS DEPENDENT ON THE

5302
03:52:32,200 --> 03:52:33,800
CULTURE CONDITIONS, WHEN YOU

5303
03:52:33,800 --> 03:52:35,920
VARY THE CULTURE CONDITIONS YOU

5304
03:52:35,920 --> 03:52:38,560
VARY THE PHENOTYPE. I'M SHOWING

5305
03:52:38,560 --> 03:52:41,080
TYPICAL PROCESS VARIABLES THAT

5306
03:52:41,080 --> 03:52:44,360
PEOPLE USE ISOLATING EXPANDING

5307
03:52:44,360 --> 03:52:46,000
MSCs FROM DIFFERENT TISSUES,

5308
03:52:46,000 --> 03:52:49,840
USING DIFFERENT MEDIA,

5309
03:52:49,840 --> 03:52:52,240
COMPOSITIONS, WHERE CELLS

5310
03:52:52,240 --> 03:52:55,240
DELIVERED TO THE RECIPIENT USING

5311
03:52:55,240 --> 03:52:58,520
DIFFERENT DELIVERY VEHICLE, ALL

5312
03:52:58,520 --> 03:52:59,680
THESE CONDITIONS HAVE POTENTIAL

5313
03:52:59,680 --> 03:53:01,680
TO IMPACT BIOLOGICAL PHENOTYPE

5314
03:53:01,680 --> 03:53:04,080
OF CELL AND INDEED THERAPEUTIC

5315
03:53:04,080 --> 03:53:05,960
ACTIVITY OF THE CELL. NEXT SLIDE

5316
03:53:05,960 --> 03:53:10,360
PLEASE.  THIS IS A SIMPLE

5317
03:53:10,360 --> 03:53:14,400
EXPERIMENT WHICH ILLUSTRATES THE

5318
03:53:14,400 --> 03:53:16,600
POUND I'M MAKING WELL MSC FROM

5319
03:53:16,600 --> 03:53:18,400
FRESH DONOR CELLS HEALTHY DONOR

5320
03:53:18,400 --> 03:53:20,520
AND EXPAND UNDER DISTINCT MEDIA

5321
03:53:20,520 --> 03:53:23,400
CONDITIONS SO SERUM FREE,

5322
03:53:23,400 --> 03:53:26,600
DIFFERENT CONFIGURATIONS,

5323
03:53:26,600 --> 03:53:29,360
DIFFERENT COMPOSITIONS OF

5324
03:53:29,360 --> 03:53:31,680
FEASIBLE EVENTS, THEY

5325
03:53:31,680 --> 03:53:33,040
PROLIFERATE WELL UNDER

5326
03:53:33,040 --> 03:53:34,360
CONDITIONS BUT LOOK AT SURFACE

5327
03:53:34,360 --> 03:53:35,360
PHENOTYPE OF THE CELLS EXPANDED

5328
03:53:35,360 --> 03:53:38,320
FROM THE SAME DONOR, DIFFERENT

5329
03:53:38,320 --> 03:53:42,000
MEDIA YOU CAN SEE BASED ON THIS

5330
03:53:42,000 --> 03:53:44,360
HEAT MAP SURFACE PHENOTYPE

5331
03:53:44,360 --> 03:53:46,680
DIFFERS DRAMATICALLY WHEN THE

5332
03:53:46,680 --> 03:53:54,960
GROWTH CONDITIONS ARE VARIED. Z

5333
03:53:54,960 --> 03:53:56,240
DIFFERENTIATION PROPENSITY OF

5334
03:53:56,240 --> 03:53:58,080
THE CELLS FROM SAME DONOR VARIES

5335
03:53:58,080 --> 03:54:00,600
WIDELY DEPENDING ON HOW THE

5336
03:54:00,600 --> 03:54:01,880
CELLS EXPAND AND I DON'T HAVE

5337
03:54:01,880 --> 03:54:05,040
THE DATA TO SHOW BUT WE KNOW THE

5338
03:54:05,040 --> 03:54:09,120
IMMUNOMODULATORY TIFTED OF THE

5339
03:54:09,120 --> 03:54:10,160
CELLS IS DIFFERENT UNDER

5340
03:54:10,160 --> 03:54:12,600
CONDITIONS THEY ARE EXPANDED. WE

5341
03:54:12,600 --> 03:54:17,480
ARE TALKING A PROCESS THAT IS

5342
03:54:17,480 --> 03:54:19,920
VARIABLE AND GIVES RISE TO CELLS

5343
03:54:19,920 --> 03:54:22,400
WITH VARIABLE PHENOTYPE, WHEN WE

5344
03:54:22,400 --> 03:54:24,160
COMPARE DIFFERENT STUDIES, THAT

5345
03:54:24,160 --> 03:54:25,080
BECOMES DIFFERENT BECAUSE WE ARE

5346
03:54:25,080 --> 03:54:28,040
NOT ASSURED OF THE CONSISTENCY

5347
03:54:28,040 --> 03:54:30,040
Z, AN STANDARDIZATION OF CELL

5348
03:54:30,040 --> 03:54:31,000
PRODUCT. THIS IS SOMETHING WE

5349
03:54:31,000 --> 03:54:33,920
NEED TO ADDRESS AND IT HASN'T

5350
03:54:33,920 --> 03:54:35,960
BEEN PROPERLY ADDRESSED TO THIS

5351
03:54:35,960 --> 03:54:37,800
DATE. NEXT SLIDE PLEASE. THIS

5352
03:54:37,800 --> 03:54:39,400
SHOWS, THIS IS REALLY IMPORTANT

5353
03:54:39,400 --> 03:54:41,520
PIECE OF INFORMATION DESPITE PIE

5354
03:54:41,520 --> 03:54:43,720
LOGICAL VARIABILITY WE SEE IN

5355
03:54:43,720 --> 03:54:46,200
THE CELL EVEN FROM THE SAME

5356
03:54:46,200 --> 03:54:47,560
DONOR WHEN UNDER DIFFERENT

5357
03:54:47,560 --> 03:54:52,080
CONDITIONS WHEN WE USE THE ISCT

5358
03:54:52,080 --> 03:54:54,200
STANDARD MARKERS NONE OF THESE

5359
03:54:54,200 --> 03:54:56,320
-- THIS BIOLOGICAL VARIABILITY

5360
03:54:56,320 --> 03:54:58,960
IS EVIDENT BECAUSE YOU SEE CD

5361
03:54:58,960 --> 03:55:02,280
73, CD 19 EQUALLY HIGHLY EXPRESS

5362
03:55:02,280 --> 03:55:04,080
IN CELLS DESPITE BIOLOGICAL

5363
03:55:04,080 --> 03:55:05,840
DIFFERENCES THAT WE SEE NEGATIVE

5364
03:55:05,840 --> 03:55:08,840
MARKERS ALL EQUALLY NEGATIVE

5365
03:55:08,840 --> 03:55:12,480
DESPITE, SO THESE MARKERS DON'T

5366
03:55:12,480 --> 03:55:16,120
FULFILL THE PURPOSE,

5367
03:55:16,120 --> 03:55:18,880
DOING/HIDING MULTITUDE OF SINS,

5368
03:55:18,880 --> 03:55:23,640
WE NEED TO CHANGE THIS. SO WE

5369
03:55:23,640 --> 03:55:27,120
HAVE TAKEN A STRONG ENGINEERING

5370
03:55:27,120 --> 03:55:31,920
APPROACH TO TRY TO STANDARDIZE

5371
03:55:31,920 --> 03:55:34,000
MANUFACTURING PROTOCOLS FOR MSC

5372
03:55:34,000 --> 03:55:35,640
DEVELOPING A FULLY ROBOTIC FULL

5373
03:55:35,640 --> 03:55:40,640
HI CLOSED AUTOMATED

5374
03:55:40,640 --> 03:55:42,000
MANUFACTURING SYSTEM WHERE NO

5375
03:55:42,000 --> 03:55:44,200
HUMAN HANDS ARE INVOLVED AND

5376
03:55:44,200 --> 03:55:46,080
ENTIRE PROCESS FROM HARVEST TO

5377
03:55:46,080 --> 03:55:48,320
TISSUE TO DONOR TO FILLING VILE

5378
03:55:48,320 --> 03:55:49,760
OF CELLS BEFORE DELIVERY TO

5379
03:55:49,760 --> 03:55:51,560
PATIENT IS CARRIED BY ROBOTIC

5380
03:55:51,560 --> 03:55:53,560
ARMS, THE MONITORING OF THE

5381
03:55:53,560 --> 03:55:55,560
STATUS OF THE CELLS IS DONE

5382
03:55:55,560 --> 03:55:58,360
REMOTELY. USING SENSORS. THIS IS

5383
03:55:58,360 --> 03:56:00,080
AN EXAMPLE, I THINK OF WHERE WE

5384
03:56:00,080 --> 03:56:02,960
NEED TO GO IN TERMS OF

5385
03:56:02,960 --> 03:56:04,720
STANDARDIZATION OF THE MSC

5386
03:56:04,720 --> 03:56:05,840
PRODUCTION METHODOLOGY. NEXT

5387
03:56:05,840 --> 03:56:09,600
SLIDE PLEASE.  SO EVERYTHING

5388
03:56:09,600 --> 03:56:12,040
DEPENDS ON ROBOTIC ARMS.

5389
03:56:12,040 --> 03:56:13,200
EVERYTHING DONE IN FULLY

5390
03:56:13,200 --> 03:56:14,880
STANDARDIZED WAY SO THERE IS NO

5391
03:56:14,880 --> 03:56:17,200
VARIATION IN THE PROCESS. FROM

5392
03:56:17,200 --> 03:56:25,840
BATCH TO BATCH. MOVE ON FROM

5393
03:56:25,840 --> 03:56:30,080
THIS. WE HAVE ALSO DEVELOPED

5394
03:56:30,080 --> 03:56:33,160
WITH ENGINEERING PARTNER A BONE

5395
03:56:33,160 --> 03:56:35,160
MARROW AUTOMATED BONE MARROW

5396
03:56:35,160 --> 03:56:39,200
HARVESTING DEVICE WHICH

5397
03:56:39,200 --> 03:56:40,320
SUCCESSFULLY CARRIES OUT THE

5398
03:56:40,320 --> 03:56:45,960
BONE MARROW BIOPSY INTO A FULLY

5399
03:56:45,960 --> 03:56:49,280
CLOSED VESSEL AND CLOSED VESSEL

5400
03:56:49,280 --> 03:56:51,280
ENTERS THE AUTOMATED PLATFORM

5401
03:56:51,280 --> 03:56:54,720
WITHOUT EXPOSURE TO THE

5402
03:56:54,720 --> 03:56:56,200
ENVIRONMENT THE SPIRE PROCESS

5403
03:56:56,200 --> 03:56:57,720
FROM THE DONOR RIGHT THROUGH TO

5404
03:56:57,720 --> 03:57:00,560
THE PATIENT FULLY CLOSED

5405
03:57:00,560 --> 03:57:02,520
AUTOMATED WITH NO OPERATOR

5406
03:57:02,520 --> 03:57:03,760
INVOLVED. THIS IS AN EXAMPLE

5407
03:57:03,760 --> 03:57:08,600
WHERE WE NEED TO GO IN TERMS OF

5408
03:57:08,600 --> 03:57:09,480
STANDARDIZING MANUFACTURING

5409
03:57:09,480 --> 03:57:10,960
PROTOCOLS. WE NEED TO

5410
03:57:10,960 --> 03:57:12,040
STANDARDIZE CONDITIONS AS WELL

5411
03:57:12,040 --> 03:57:14,680
IN TERMS OF MEDIA AND IDEAL LIE

5412
03:57:14,680 --> 03:57:18,080
USING DEFINED XENOFREE MEDIA

5413
03:57:18,080 --> 03:57:19,760
RATHER THAN MEDIA CONTAINING

5414
03:57:19,760 --> 03:57:22,080
BIOLOGICAL SUPPLEMENTS.  IN

5415
03:57:22,080 --> 03:57:23,760
TERMS OF MECHANISM OF ACTION, I

5416
03:57:23,760 --> 03:57:26,480
RUN THROUGH THIS QUICKLY BECAUSE

5417
03:57:26,480 --> 03:57:27,800
IN THE INTEREST OF TIME, WE HAVE

5418
03:57:27,800 --> 03:57:30,320
TAKEN TWO APPROACHES. TO TRY TO

5419
03:57:30,320 --> 03:57:32,120
UNDERSTAND MECHANISM OF ACTION.

5420
03:57:32,120 --> 03:57:34,840
THESE ARE BOTH BASED ON THE

5421
03:57:34,840 --> 03:57:36,200
PREMISE THAT WHAT IS REALLY

5422
03:57:36,200 --> 03:57:38,600
IMPORTANT IS PHENOTYPE OF THE

5423
03:57:38,600 --> 03:57:43,280
CELL ONCE EXPOSED TO THE DISEASE

5424
03:57:43,280 --> 03:57:45,200
ENVIRONMENT. LOOKING AT THE

5425
03:57:45,200 --> 03:57:47,200
PHENOTYPE OF CELL IN PLASTIC

5426
03:57:47,200 --> 03:57:49,080
DISH ISN'T GOING TO TELL US HOW

5427
03:57:49,080 --> 03:57:50,520
THE CELL RESPONDS. ONCE

5428
03:57:50,520 --> 03:57:52,000
TRANSPLANTED TO THE IN VIVO

5429
03:57:52,000 --> 03:57:53,200
ENVIRONMENT, WE NEED TO

5430
03:57:53,200 --> 03:57:54,720
UNDERSTAND THE RESPONSE OF

5431
03:57:54,720 --> 03:57:57,480
SURGERY IN VIVO ENVIRONMENT. WE

5432
03:57:57,480 --> 03:57:59,080
CAN DO THAT TWO WAYS BY TRYING

5433
03:57:59,080 --> 03:58:01,640
TO REPLICATE IN VIVO ENVIRONMENT

5434
03:58:01,640 --> 03:58:03,640
IN VITRO EXPERIMENTS SO CALLED

5435
03:58:03,640 --> 03:58:05,520
LICENSING AND THAT IS WHAT I

5436
03:58:05,520 --> 03:58:12,800
WILL TALK ABOUT HERE IN THE NEXT

5437
03:58:12,800 --> 03:58:15,840
SLIDE. WE CAN DEVELOP CONDITIONS

5438
03:58:15,840 --> 03:58:17,960
WHERE WE TRY TO REPLICATE IN

5439
03:58:17,960 --> 03:58:19,640
VIVO ENVIRONMENT USING

5440
03:58:19,640 --> 03:58:24,080
INFLAMMATORY SITE CYTOKINES IL 1

5441
03:58:24,080 --> 03:58:25,760
BETA, HYPOXIA, THEN LOOK AT THE

5442
03:58:25,760 --> 03:58:28,880
RESPONSE OF THE CELLS TO THIS

5443
03:58:28,880 --> 03:58:30,560
TIME OF CONDITIONING THAT THIS

5444
03:58:30,560 --> 03:58:32,480
IS POTENTIAL TO PREDICT HOW

5445
03:58:32,480 --> 03:58:37,120
CELLS RESPOND AND DELIVERED TO

5446
03:58:37,120 --> 03:58:38,760
THE ENVIRONMENT WITH OA JOINTS. 

5447
03:58:38,760 --> 03:58:40,320
WE HAVE DONE THIS WITH BOP

5448
03:58:40,320 --> 03:58:42,440
MARROW DERIVED CELLS TAKEN FROM

5449
03:58:42,440 --> 03:58:45,080
THE SAME DONOR TO TRY TO

5450
03:58:45,080 --> 03:58:48,040
UNDERSTAND IN A WELL DESIGNED

5451
03:58:48,040 --> 03:58:50,520
EXPERIMENT, THE VARIABLE

5452
03:58:50,520 --> 03:58:51,480
RESPONSE OF CELLS FROM DIFFERENT

5453
03:58:51,480 --> 03:58:55,160
SOURCES.  WITHOUT GOING THROUGH

5454
03:58:55,160 --> 03:59:00,080
THE DATA IN TOO MUCH DETAIL,

5455
03:59:00,080 --> 03:59:02,800
TAKE HOME MESSAGE IS THERE IS A

5456
03:59:02,800 --> 03:59:04,040
CHANGE IN PHENOTYPE OF CELLS

5457
03:59:04,040 --> 03:59:05,880
WHEN EXPOSED TO THESE

5458
03:59:05,880 --> 03:59:11,080
INFLAMMATORY CYTOKINES, IN

5459
03:59:11,080 --> 03:59:12,920
GENERAL TERMS ADIPOSE DERIVED

5460
03:59:12,920 --> 03:59:18,680
CELLS PRODUCE MORE

5461
03:59:18,680 --> 03:59:20,880
ANTI-INFLAMMATORY CYTOKINES,

5462
03:59:20,880 --> 03:59:24,440
THAN BONE MARROW CELLS SO THINK

5463
03:59:24,440 --> 03:59:25,000
THERAPEUTIC EWE UNTIL I HAVE

5464
03:59:25,000 --> 03:59:27,560
THESE CELLS BASED ON THESE

5465
03:59:27,560 --> 03:59:29,040
EXPERIMENTS THE RUG ROLLS

5466
03:59:29,040 --> 03:59:30,440
SUGGEST ADIPOSE DERIVED CELLS

5467
03:59:30,440 --> 03:59:32,760
ARE MORE USEFUL THAN BONE MARROW

5468
03:59:32,760 --> 03:59:36,680
DERIVED ESPECIALLY IN CONTEXT OF

5469
03:59:36,680 --> 03:59:38,640
ANTI-INFLAMMATORY CYTOKINES

5470
03:59:38,640 --> 03:59:41,280
ANGIOGENIC FACTORS AND ALSO

5471
03:59:41,280 --> 03:59:43,080
NEUROTROPIC FACTORS. IF I CAN

5472
03:59:43,080 --> 03:59:48,440
MOVE TO THE NEXT SLIDE.  THIS

5473
03:59:48,440 --> 03:59:49,640
SHOWS RELEASE INFLAMMATORY

5474
03:59:49,640 --> 03:59:51,520
MOLECULE BUSINESS THE CELLS AN

5475
03:59:51,520 --> 03:59:53,960
EXPOSED TO THESE LICENSING

5476
03:59:53,960 --> 03:59:55,440
CONDITIONS YOU CAN SEE THE

5477
03:59:55,440 --> 03:59:57,640
ADIPOSE DERIVED CELLS

5478
03:59:57,640 --> 03:59:59,200
QUANTITATIVELY HAD PA HIGHER

5479
03:59:59,200 --> 04:00:03,920
RESPONSE. MOVING ON THE SAME IS

5480
04:00:03,920 --> 04:00:09,560
CASE WITH CHEMOKINE RELEASE AND

5481
04:00:09,560 --> 04:00:11,560
NEXT SLIDE, ALSO WITH PRO

5482
04:00:11,560 --> 04:00:12,680
ANGIOGENIC FACTORS. THE NEXT

5483
04:00:12,680 --> 04:00:17,520
SLIDE.  THE SECOND EXPERIMENTAL

5484
04:00:17,520 --> 04:00:19,480
STRATEGY IN TERMS OF

5485
04:00:19,480 --> 04:00:20,200
UNDERSTANDING MECHANISM OF

5486
04:00:20,200 --> 04:00:23,280
ACTION IS THROUGH THE FOLLOWING.

5487
04:00:23,280 --> 04:00:29,120
SO WE DELIVER CELLS TO OA JOINT

5488
04:00:29,120 --> 04:00:31,360
TYPICALLY A MOUSE MODEL

5489
04:00:31,360 --> 04:00:32,600
OSTEOARTHRITIS FLUORESCENTLY

5490
04:00:32,600 --> 04:00:35,120
LABELED THEN SUBSEQUENT TIME

5491
04:00:35,120 --> 04:00:39,360
POINTS WE RETRIEVE CELLS FROM

5492
04:00:39,360 --> 04:00:42,040
THE JOINT TO UNDERSTAND HAPPEN

5493
04:00:42,040 --> 04:00:43,120
TYPE OF CELLS ARE MODULATED

5494
04:00:43,120 --> 04:00:46,320
DURING TIME OF RESIDING WITH OA

5495
04:00:46,320 --> 04:00:48,000
JOINTS SO TRANSPLANTED STUDIES

5496
04:00:48,000 --> 04:00:50,440
ARE USEFUL AND WE LEARNED ABOUT

5497
04:00:50,440 --> 04:00:51,760
THE BEHAVIOR OF THE CELLS SO WE

5498
04:00:51,760 --> 04:00:53,440
HAVE DONE THIS IN A NUMBER OF

5499
04:00:53,440 --> 04:00:56,600
DIFFERENT EXPERIMENTAL

5500
04:00:56,600 --> 04:00:58,120
STRATEGIES, WE ARE JUST PUTTING

5501
04:00:58,120 --> 04:01:01,840
THE RESULTS TOGETHER NOW. AND

5502
04:01:01,840 --> 04:01:03,640
SUBMITTING THE WORK. BUT WHAT WE

5503
04:01:03,640 --> 04:01:06,760
FOUND IS THERE IS A SIGNIFICANT

5504
04:01:06,760 --> 04:01:08,880
DIFFERENCE IN GENE EXPRESSION

5505
04:01:08,880 --> 04:01:11,280
PROFILES BETWEEN CELLS THAT ARE

5506
04:01:11,280 --> 04:01:15,280
RETRIEVED FROM THE CELLS

5507
04:01:15,280 --> 04:01:18,680
DELIVERED. NEXT SLIDE PLEASE. SO

5508
04:01:18,680 --> 04:01:20,600
WE WERE ABLE TO EXTRACT CELLS

5509
04:01:20,600 --> 04:01:23,560
PURIFY THEM FROM THE OA JOINTS

5510
04:01:23,560 --> 04:01:28,200
BACK INTO CULTURE UNDERSTAND

5511
04:01:28,200 --> 04:01:29,760
ABOUT THEIR CHRONOGENICITY AND

5512
04:01:29,760 --> 04:01:32,960
PHENOTYPE AND LOOK AT PROFILES

5513
04:01:32,960 --> 04:01:34,800
IN THE RETRIEVED CELLS VERSUS

5514
04:01:34,800 --> 04:01:38,400
CONTROL CELLS. WE CAN LOOK AT

5515
04:01:38,400 --> 04:01:41,640
THE GENE PATHWAYS THAT ARE

5516
04:01:41,640 --> 04:01:46,360
ACTIVATED BY CELLS DURING TIME

5517
04:01:46,360 --> 04:01:47,720
RESIDE WITHIN OA JOINT AND THIS

5518
04:01:47,720 --> 04:01:50,720
IS A SNAP SHOT WE SEE

5519
04:01:50,720 --> 04:01:51,720
SIGNIFICANT CHANGES IN

5520
04:01:51,720 --> 04:01:53,080
BIOLOGICAL PROFILE OR PHENOTYPE

5521
04:01:53,080 --> 04:01:55,120
OF THE CELLS, THAT WE RETRIEVE

5522
04:01:55,120 --> 04:01:58,640
FROM THE JOINTS, SEEMS THOSE

5523
04:01:58,640 --> 04:02:02,160
CELLS WHICH PERSIST WE CAN

5524
04:02:02,160 --> 04:02:04,800
RETRIEVE FROM THE OA JOINT HAVE

5525
04:02:04,800 --> 04:02:07,440
MUCH MORE PROGENITOR PHENOTYPE

5526
04:02:07,440 --> 04:02:10,600
THAN STARTING POPULATION AS IF

5527
04:02:10,600 --> 04:02:13,240
THE EXPOSURE TO OA ENVIRONMENT

5528
04:02:13,240 --> 04:02:14,560
SELECTS FOR THIS PHENOTYPE SO

5529
04:02:14,560 --> 04:02:16,360
THAT IS REFLECTED IN THE GENE

5530
04:02:16,360 --> 04:02:18,440
PATHWAY THAT WE ARE SEEING HERE

5531
04:02:18,440 --> 04:02:20,400
LOOKING AT EXTRA CELLULAR MATRIX

5532
04:02:20,400 --> 04:02:21,280
ORGANIZATION, POST TRANSLATION

5533
04:02:21,280 --> 04:02:23,640
HAL MODIFICATION AND SO ON. SO

5534
04:02:23,640 --> 04:02:24,880
THESE ARE INTERESTING, THEY ARE

5535
04:02:24,880 --> 04:02:27,080
NOT DONE YET BUT THEY WILL HELP

5536
04:02:27,080 --> 04:02:30,120
US TO SHED LIGHT ON THE

5537
04:02:30,120 --> 04:02:33,760
MECHANISM OF ACTION. SO ON THE

5538
04:02:33,760 --> 04:02:36,320
BASIS OF WHAT I TALKED ABOUT

5539
04:02:36,320 --> 04:02:37,200
CLINICAL TRIALS MANUFACTURING

5540
04:02:37,200 --> 04:02:38,760
TECHNOLOGY AND MECHANISM OF

5541
04:02:38,760 --> 04:02:41,640
ACTION HAVE COME UP WITH

5542
04:02:41,640 --> 04:02:44,840
RECOMMENDATIONS WHICH REPRESENT

5543
04:02:44,840 --> 04:02:45,800
-- (OVERLAPPING SPEAKERS) SHARE

5544
04:02:45,800 --> 04:02:49,760
THEM. IN THE FIRST INSTANCE

5545
04:02:49,760 --> 04:02:51,640
FOCUS ON STANDARD MANUFACTURING

5546
04:02:51,640 --> 04:02:54,400
AND THERE'S BEEN NO ATTEMPT AT

5547
04:02:54,400 --> 04:02:56,960
ALL TO STANDARDIZE MANUFACTURING

5548
04:02:56,960 --> 04:03:01,320
OF CELLS WE DO NEED TO DEVELOP

5549
04:03:01,320 --> 04:03:02,280
-- (OVERLAPPING SPEAKERS)

5550
04:03:02,280 --> 04:03:04,320
>>THAT IS ONE THING --

5551
04:03:04,320 --> 04:03:05,920
>>SOMEBODY'S VOICE IS
COMING

5552
04:03:05,920 --> 04:03:07,040
THROUGH HERE. BUT I'M ALMOST

5553
04:03:07,040 --> 04:03:10,280
DONE. CONSISTENT MANUFACTURING

5554
04:03:10,280 --> 04:03:11,920
MODELS WITH DEFINED MEDIA ARE

5555
04:03:11,920 --> 04:03:13,560
CRITICAL THINGS TO PAY

5556
04:03:13,560 --> 04:03:15,800
ATTENTIATTENTION. THESE SAME STS

5557
04:03:15,800 --> 04:03:17,200
FORWARD PRETTY EVERY DAY

5558
04:03:17,200 --> 04:03:19,080
QUESTIONS, BUT THEY HAVE NOT

5559
04:03:19,080 --> 04:03:22,040
BEEN PROPERLY ADDRESSED.  WE

5560
04:03:22,040 --> 04:03:24,720
NEED AN INTERNATIONAL STANDARD

5561
04:03:24,720 --> 04:03:27,600
TO DEFINE MSC FOR THERAPEUTIC

5562
04:03:27,600 --> 04:03:28,840
USE THOUGH ATTEMPTS MADE IN THE

5563
04:03:28,840 --> 04:03:30,400
PAST TO ACHIEVE IT, IT'S NOTE

5564
04:03:30,400 --> 04:03:32,600
BEEN SUCCESSFUL SO IT MIGHT BE

5565
04:03:32,600 --> 04:03:35,920
POSSIBLE FOR THE ORGANIZATIONS

5566
04:03:35,920 --> 04:03:39,640
LISTED HERE FDA TO SOMEHOW GET

5567
04:03:39,640 --> 04:03:40,840
TOGETHER TO DRIVE QUESTION

5568
04:03:40,840 --> 04:03:43,480
FORWARD, IT IS YOU ARE GENERALLY

5569
04:03:43,480 --> 04:03:45,800
NEEDED BECAUSE WE ARE NOT ABLE

5570
04:03:45,800 --> 04:03:47,480
TO INTERPRET THE CLINICAL TRIAL

5571
04:03:47,480 --> 04:03:50,160
DATA PROPERLY UNTIL WE HAVE

5572
04:03:50,160 --> 04:03:51,400
CONFIDENCE IN THE CONSISTENCY OF

5573
04:03:51,400 --> 04:03:52,720
MANUFACTURING OF CELL. WE NEED

5574
04:03:52,720 --> 04:03:55,800
TO ESTABLISH NEW SET OF CRITICAL

5575
04:03:55,800 --> 04:03:58,600
QUALITY ATTRIBUTES FOR RELEASE,

5576
04:03:58,600 --> 04:04:01,680
BIOLOGICALLY MEANINGFUL AND DO

5577
04:04:01,680 --> 04:04:02,840
TELL SOMETHING REALISTIC ABOUT

5578
04:04:02,840 --> 04:04:04,480
THE CELL SO KNEW DISEASE

5579
04:04:04,480 --> 04:04:07,320
SPECIFIC POTENCY TESTS ARE CLEAR

5580
04:04:07,320 --> 04:04:09,320
PREDICTIVE VALUE WE DON'T HAVE

5581
04:04:09,320 --> 04:04:13,080
CURRENTLY. MY OPINION WE NEED TO

5582
04:04:13,080 --> 04:04:15,320
RESCIND ISCT RECOMMENDATIONS

5583
04:04:15,320 --> 04:04:17,080
BECAUSE THEY ARE NOT INFORMATIVE

5584
04:04:17,080 --> 04:04:22,320
BUT ALSO HIDING PROBLEMS.  THIRD

5585
04:04:22,320 --> 04:04:24,680
QUARTER THEN THINK ABOUT

5586
04:04:24,680 --> 04:04:26,320
PRODUCING LARGE SCALE ALLOGENEIC

5587
04:04:26,320 --> 04:04:30,160
USE IT IS POSSIBLE TO THINK

5588
04:04:30,160 --> 04:04:32,440
ABOUT ELABORATE BIOLOGICAL SO

5589
04:04:32,440 --> 04:04:37,000
YOU CAN AFFORD TO INVEST LARGE

5590
04:04:37,000 --> 04:04:39,080
ARRAY OF TESTS TO GET MAXIMUM

5591
04:04:39,080 --> 04:04:40,840
AMOUNT OF BIOLOGICAL

5592
04:04:40,840 --> 04:04:42,240
INFORMATION. GENOMIC SEQUENCING

5593
04:04:42,240 --> 04:04:47,280
SINGLE CELL SEQUENCING MENTIONED

5594
04:04:47,280 --> 04:04:48,320
ALREADY, IMMUNE ET CETERA. WE

5595
04:04:48,320 --> 04:04:50,560
CAN AFFORD TO DO THESE TESTS,

5596
04:04:50,560 --> 04:04:55,840
THIS IS WHAT WE NEED IN TERMS OF

5597
04:04:55,840 --> 04:04:57,520
PROPER CRITERIA. IN TERMS OF

5598
04:04:57,520 --> 04:04:59,000
MECHANISM OF ACTION WE NEED MORE

5599
04:04:59,000 --> 04:05:01,240
INSIGHT INTO WHAT THE CELLS ARE

5600
04:05:01,240 --> 04:05:04,280
ACTUALLY DOING WHEN DELIVERD TO

5601
04:05:04,280 --> 04:05:06,840
THE HOST AND WE NEED TO BE

5602
04:05:06,840 --> 04:05:07,760
CAREFUL TO DISTINGUISH BETWEEN

5603
04:05:07,760 --> 04:05:09,760
LOCAL DELIVERY AND SYSTEMIC

5604
04:05:09,760 --> 04:05:12,520
DELIVERY BECAUSE LOCAL DELIVERY

5605
04:05:12,520 --> 04:05:14,120
AND -- GIVES RISE TO DIFFERENT

5606
04:05:14,120 --> 04:05:15,520
SET OF RESPONSES COMPARED TO

5607
04:05:15,520 --> 04:05:18,920
SYSTEMIC DELIVERY. SO LET ME

5608
04:05:18,920 --> 04:05:20,760
FINISH THERE. THANK YOU ALL VERY

5609
04:05:20,760 --> 04:05:25,720
MUCH FOR YOUR ATTENTION.

5610
04:05:25,720 --> 04:05:28,000
>>BEAUTIFUL TALK RIGHT
BACK TO

5611
04:05:28,000 --> 04:05:28,720
CONNIE CHU'S TALK AT THE

5612
04:05:28,720 --> 04:05:30,680
BEGINNING THE TREMENDOUS

5613
04:05:30,680 --> 04:05:31,560
HETEROGENEITY ALL THESE

5614
04:05:31,560 --> 04:05:32,680
FORMULATIONS MAKES IT SO

5615
04:05:32,680 --> 04:05:34,440
CHALLENGING TO STUDY THEM AND

5616
04:05:34,440 --> 04:05:36,640
THE NEED TO CHARACTERIZE

5617
04:05:36,640 --> 04:05:40,720
IDENTIFY SENTINEL MARKERS OF

5618
04:05:40,720 --> 04:05:42,480
POTENCY PURE REACTIVITY. YOU

5619
04:05:42,480 --> 04:05:45,280
MAKE IMPORTANT POINT ABOUT

5620
04:05:45,280 --> 04:05:46,400
ALLOGENEIC PREPARATIONS ALLOW US

5621
04:05:46,400 --> 04:05:49,400
TO DO THAT, NOT PRACTICAL TO DON

5622
04:05:49,400 --> 04:05:51,080
AUTOLOGOUS TISSUE. HOW MANY DAYS

5623
04:05:51,080 --> 04:05:53,720
IS CULTURE EXPANSION YOU USE?

5624
04:05:53,720 --> 04:05:57,280
>>FOR AUTOLOGOUS STUDY 14
DAYS

5625
04:05:57,280 --> 04:05:59,240
FROM HARVESTING THE MATERIAL TO

5626
04:05:59,240 --> 04:06:00,480
DELIVERING THE CELL BACK TO THE

5627
04:06:00,480 --> 04:06:03,200
PATIENT. IT WAS A MAXIMUM OF 14

5628
04:06:03,200 --> 04:06:11,240
DAYS.

5629
04:06:11,240 --> 04:06:15,400
>>PAM HAS HER HAND UP.

5630
04:06:15,400 --> 04:06:18,200
>>THANK YOU,
COMPREHENSIVE

5631
04:06:18,200 --> 04:06:19,920
OVERVIEW OF THE CHALLENGES. ONE

5632
04:06:19,920 --> 04:06:21,560
QUESTION IN TERMS OF EXPERIMENTS

5633
04:06:21,560 --> 04:06:25,520
WITH LICENSING CELLS, VERSUS

5634
04:06:25,520 --> 04:06:29,360
THOSE YOU RETRIEVE FROM IN VIVO

5635
04:06:29,360 --> 04:06:30,720
EXPERIENCE, HAVE YOU HAD

5636
04:06:30,720 --> 04:06:33,640
COMPARISON BETWEEN THE TWO IN

5637
04:06:33,640 --> 04:06:35,400
TERMS OF GENE EXPRESSION

5638
04:06:35,400 --> 04:06:37,400
ANALYSIS WHAT IS UP AND DOWN IN

5639
04:06:37,400 --> 04:06:38,400
THOSE TWO DIFFERENT TYPES OF

5640
04:06:38,400 --> 04:06:40,480
POPULATIONS?

5641
04:06:40,480 --> 04:06:44,720
>>BROADLY SPEAKING THERE
IS TWO

5642
04:06:44,720 --> 04:06:46,640
SETS OF GENES UPREGULATED IN

5643
04:06:46,640 --> 04:06:50,960
BOTH SETS OF EXPERIMENTS. GENES

5644
04:06:50,960 --> 04:06:53,680
CALLING FOR ANTI-INFLAMMATORY

5645
04:06:53,680 --> 04:06:55,240
PROTEINS AND GENES CALLING FOR

5646
04:06:55,240 --> 04:06:57,800
SECRETED PROTEINS ARE DOMINANTLY

5647
04:06:57,800 --> 04:06:59,520
UPREGULATED SO PARACRINE

5648
04:06:59,520 --> 04:07:01,320
RESPONSE OF THE CELLS IS HIGHLY

5649
04:07:01,320 --> 04:07:04,160
MODULATED BY BOTH IN VITRO

5650
04:07:04,160 --> 04:07:05,560
LICENSING ENVIRONMENT AND IN

5651
04:07:05,560 --> 04:07:07,680
VIVO OA ENVIRONMENT. I WOULD SAY

5652
04:07:07,680 --> 04:07:10,640
WE ARE NOT DONE WITH THIS

5653
04:07:10,640 --> 04:07:14,040
ANALYSIS YET. SO WE DON'T HAVE

5654
04:07:14,040 --> 04:07:23,720
THE FINAL STORY YET.

5655
04:07:23,720 --> 04:07:25,680
>>SECOND QUESTION ABOUT
TWO

5656
04:07:25,680 --> 04:07:27,120
PREVIOUS TRIALS, THERE'S

5657
04:07:27,120 --> 04:07:28,000
RESPONDER PATIENT AND

5658
04:07:28,000 --> 04:07:29,680
NON-RESPONDER PATIENTS, COULD BE

5659
04:07:29,680 --> 04:07:30,560
BECAUSE OF THE PATIENT CONDITION

5660
04:07:30,560 --> 04:07:34,720
BUT IT ALSO COULD BE BECAUSE OF

5661
04:07:34,720 --> 04:07:36,520
THE CELL PRODUCT. ARE YOU ABLE

5662
04:07:36,520 --> 04:07:41,040
TO LOOK AT PRODUCT GIVEN TO

5663
04:07:41,040 --> 04:07:43,440
RESPONDERS TO SEE IF THERE WAS A

5664
04:07:43,440 --> 04:07:46,400
PATTERN IN THAT, THAT WAS LIKE A

5665
04:07:46,400 --> 04:07:46,880
COMMON THEME?

5666
04:07:46,880 --> 04:07:52,080
>>THAT IS PART OF THE
STUDY,

5667
04:07:52,080 --> 04:07:56,680
TRYING TO COMPARE THE SUB

5668
04:07:56,680 --> 04:07:57,680
PREPARATION CLINICAL OUTCOME,

5669
04:07:57,680 --> 04:07:59,680
BECAUSE THE STUDY IS BLINDED WE

5670
04:07:59,680 --> 04:08:01,720
DON'T KNOW WHERE IT WILL GO BUT

5671
04:08:01,720 --> 04:08:03,200
IT IS DONE FOR SURE.

5672
04:08:03,200 --> 04:08:05,640
>>FOR THE FIRST TRIAL, IS
THAT

5673
04:08:05,640 --> 04:08:05,920
AVAILABLE?

5674
04:08:05,920 --> 04:08:08,880
>>AVAILABLE IN LIMITED
WAY FOR

5675
04:08:08,880 --> 04:08:10,440
THE FIRST TRIAL BUT I THINK

5676
04:08:10,440 --> 04:08:13,200
THERE WASN'T ENOUGH PATIENTS TO

5677
04:08:13,200 --> 04:08:16,160
BE CONCLUSIVE ABOUT THAT. IN

5678
04:08:16,160 --> 04:08:21,040
FACT, IN THE GROUP I HAD 506 WAS

5679
04:08:21,040 --> 04:08:26,480
POSITIVE AND ONE WAS NEGATIVE SO

5680
04:08:26,480 --> 04:08:27,200
SNEAD MORE PATIENT DATA TO DO

5681
04:08:27,200 --> 04:08:37,720
THAT PROPERLY.  FORGIVE ME IF I

5682
04:08:43,920 --> 04:08:44,720
MISINTERPRETED THE DRUG

5683
04:08:44,720 --> 04:08:45,760
DEVELOPMENT PATHWAYS THAT YOU

5684
04:08:45,760 --> 04:08:47,480
ARE PURSUING. I KNOW THE TRIALS

5685
04:08:47,480 --> 04:08:49,680
ARE NOT BEING PERFORMED IN THE

5686
04:08:49,680 --> 04:08:52,640
STATES BUT YOU MENTIONED GOING

5687
04:08:52,640 --> 04:08:55,440
FROM AUTOLOGOUS CELLS PHASE 2 TO

5688
04:08:55,440 --> 04:08:57,080
POSSIBLY SWITCHING OVER TO ALLO

5689
04:08:57,080 --> 04:09:01,120
IN PHASE 3, WHAT IS THE

5690
04:09:01,120 --> 04:09:05,120
REGULATORY PLAN FOR THAT

5691
04:09:05,120 --> 04:09:07,560
APPROACH GIVEN IT WILL LIKELY BE

5692
04:09:07,560 --> 04:09:10,120
CLASSIFIED A DIFFERENT BIOLOGICS

5693
04:09:10,120 --> 04:09:12,920
ONCE YOU KNOW FROM ALLO SORRY

5694
04:09:12,920 --> 04:09:14,440
FROM AUTO TO ALLO?

5695
04:09:14,440 --> 04:09:17,080
>>I HAVE TO BE HONEST, WE
DON'T

5696
04:09:17,080 --> 04:09:18,080
YET KNOW WHAT THE REGULATORY

5697
04:09:18,080 --> 04:09:19,760
RESPONSE TO THIS REQUEST IS

5698
04:09:19,760 --> 04:09:23,120
GOING TO BE. IT IS BASED ON THE

5699
04:09:23,120 --> 04:09:27,720
FACT WE KNOW LARGE SCALE USE OF

5700
04:09:27,720 --> 04:09:29,600
AUTOLOGOUS EXPANDED CELLS IS

5701
04:09:29,600 --> 04:09:31,040
IMPRACTICAL AND NEXT TO

5702
04:09:31,040 --> 04:09:33,000
IMPOSSIBLE TO ACHIEVE. IT IS TOO

5703
04:09:33,000 --> 04:09:35,280
COSTLY AND LOGISTICS ARE TOO

5704
04:09:35,280 --> 04:09:36,440
COMPLICATED SO IF WE PROCEED

5705
04:09:36,440 --> 04:09:37,760
WITH THIS, WE HAVE TO MAKE THAT

5706
04:09:37,760 --> 04:09:40,960
SWITCH FROM AUTOLOGOUS TO

5707
04:09:40,960 --> 04:09:50,200
ALLOGENEIC. ARE NOT ALLOWED TO

5708
04:09:50,200 --> 04:09:51,600
SAY WHAT THE REGULATOR WOULD

5709
04:09:51,600 --> 04:09:55,440
REQUIRE EXCEPT WIDE USE OF AL

5710
04:09:55,440 --> 04:09:56,880
ALLOGENEIC CELL THERAPY APPROVED

5711
04:09:56,880 --> 04:09:58,560
IN EUROPE AND AT LEAST ONE OTHER

5712
04:09:58,560 --> 04:10:02,000
INDICATION SO WE MAY HOPEFULLY

5713
04:10:02,000 --> 04:10:05,960
RELY ON THAT EXPERIENCE. WE MAY

5714
04:10:05,960 --> 04:10:09,280
HAVE TO GO BACK AND DO

5715
04:10:09,280 --> 04:10:10,680
COMPARISON STUDIES BUT WE ARE

5716
04:10:10,680 --> 04:10:12,040
NOT CERTAIN YET ABOUT HOW IT

5717
04:10:12,040 --> 04:10:22,200
WILL GO. 

5718
04:10:25,960 --> 04:10:28,080
>>MARVELOUS TALK, LOVE
THE TALK

5719
04:10:28,080 --> 04:10:30,960
MORE ABOUT AUTOMATION. MY

5720
04:10:30,960 --> 04:10:33,680
QUESTION I WILL ASK HERE IS ONE,

5721
04:10:33,680 --> 04:10:36,040
YOU MENTIONED THAT GENERAL

5722
04:10:36,040 --> 04:10:38,080
DISFASHION WITH THE ISCT

5723
04:10:38,080 --> 04:10:40,640
GUIDELINES WHICH ARE WELL

5724
04:10:40,640 --> 04:10:44,040
INTENTIONED BUT PRIMARILY

5725
04:10:44,040 --> 04:10:46,360
FOCUSED ON TECHNOLOGY AT THE

5726
04:10:46,360 --> 04:10:48,360
TIME, FLOW CYTOMETRY. WE NOW AS

5727
04:10:48,360 --> 04:10:50,800
YOU POINT OUT HAVE NOT

5728
04:10:50,800 --> 04:10:53,640
INEXPENSIVE BUT SINGLE CELL RNA

5729
04:10:53,640 --> 04:10:55,760
SEQ AND SINGLE CELL ANALYSIS ARE

5730
04:10:55,760 --> 04:10:58,320
DONE LARGER SCALE. ARE YOU READY

5731
04:10:58,320 --> 04:11:01,960
TO GIVE UP ON FLOW CYTOMETRY OR

5732
04:11:01,960 --> 04:11:04,000
-- AND JUST FOCUS ON THE OTHER

5733
04:11:04,000 --> 04:11:08,560
TWO OMIC STRATEGIE STRATEGIES? E

5734
04:11:08,560 --> 04:11:10,320
QUESTION. SECOND, THIS VARIATION

5735
04:11:10,320 --> 04:11:16,960
YOU HAVE DEMONSTRATED, BETWEEN

5736
04:11:16,960 --> 04:11:17,640
MSC BATCHES AND CULTURE

5737
04:11:17,640 --> 04:11:19,360
CONDITIONS, HOW MUCH OF THAT IS

5738
04:11:19,360 --> 04:11:23,440
CLONAL SELECTION AMONG

5739
04:11:23,440 --> 04:11:26,320
POLYCLONAL MSC POPULATION AND

5740
04:11:26,320 --> 04:11:27,240
HAVE YOU BEEN ABLE TO LOOK AT

5741
04:11:27,240 --> 04:11:29,120
THAT?

5742
04:11:29,120 --> 04:11:31,920
>>IN RELATION TO THE
FIRST

5743
04:11:31,920 --> 04:11:37,200
POINT I AGREE THE ISCT STANDARDS

5744
04:11:37,200 --> 04:11:40,240
WHEN PUBLISHED THE INTENTION WAS

5745
04:11:40,240 --> 04:11:45,160
VERY CLEAR. I THINK THE ISCT HAS

5746
04:11:45,160 --> 04:11:46,920
MADE SOME NEW RECOMMENDATIONS IN

5747
04:11:46,920 --> 04:11:48,800
RELATION TO THIS BUT THE FIRST

5748
04:11:48,800 --> 04:11:51,760
SET OF MARKERS STILL STICK AND

5749
04:11:51,760 --> 04:11:54,640
EVERY SINGLE PIECE OF

5750
04:11:54,640 --> 04:11:58,280
INFORMATION YOU SEE ABOUT MSC

5751
04:11:58,280 --> 04:12:00,320
INVOLVE IT IS SAME MARKERS,

5752
04:12:00,320 --> 04:12:02,960
BECAUSE THEY ARE EASY TO DO,

5753
04:12:02,960 --> 04:12:04,720
ALWAYS POSITIVE SO THEY GIVE

5754
04:12:04,720 --> 04:12:10,800
THIS SENSE OF SORT OF SENSE OF

5755
04:12:10,800 --> 04:12:12,080
CONFIDENCE WHICH IS NOT

5756
04:12:12,080 --> 04:12:16,480
MISPLACED. I THINK WE CAN'T

5757
04:12:16,480 --> 04:12:18,240
AFFORD TO GIVE UP FLOW

5758
04:12:18,240 --> 04:12:20,560
CYTOMETRY, IF IT IS LARGE SCALE

5759
04:12:20,560 --> 04:12:23,120
ALLOGENEIC, WE CAN AFFORD TO

5760
04:12:23,120 --> 04:12:25,280
INVEST HEAVILY IN ELABORATE

5761
04:12:25,280 --> 04:12:27,440
MATRIX OF TESTS.  JUST NEED TO

5762
04:12:27,440 --> 04:12:29,840
EXPAND CHARACTERIZATION OF

5763
04:12:29,840 --> 04:12:31,600
SURFACE PHENOTYPE MORE THAN

5764
04:12:31,600 --> 04:12:33,120
MARKERS WE ARE TALKING ABOUT.

5765
04:12:33,120 --> 04:12:34,720
PROBABLY SINGLE CELL SEQUENCING

5766
04:12:34,720 --> 04:12:36,960
OF THE PREPARATIONS TO SOMEHOW

5767
04:12:36,960 --> 04:12:38,720
DEVELOP STANDARD AROUND THAT. 

5768
04:12:38,720 --> 04:12:40,560
BENEED TO DO THE BIOLOGICAL

5769
04:12:40,560 --> 04:12:43,080
ASSAYS THAT RELATED TO POTENCY,

5770
04:12:43,080 --> 04:12:44,400
WHICH WE HAVEN'T BEEN DOING

5771
04:12:44,400 --> 04:12:46,800
BECAUSE THERE ARE POTENT AND SUB

5772
04:12:46,800 --> 04:12:47,880
POTENT BATCHES, RIGHT NOW WE ARE

5773
04:12:47,880 --> 04:12:50,040
NOT ABLE TO TELL WHICH IS WHICH.

5774
04:12:50,040 --> 04:12:51,240
SO WE DON'T KNOW ENOUGH ABOUT

5775
04:12:51,240 --> 04:12:52,360
THE CELLS, WE ARE DELIVERING TO

5776
04:12:52,360 --> 04:12:55,440
THE PATIENTS IN THESE STUDIES.

5777
04:12:55,440 --> 04:12:59,080
THAT IS LARGE EXTENT OF VARIABLE

5778
04:12:59,080 --> 04:13:00,200
OUTCOMES BECAUSE THE PRODUCT IS

5779
04:13:00,200 --> 04:13:05,520
VARIABLE. LARISSA.

5780
04:13:05,520 --> 04:13:09,360
>>THANK YOU. SO I NOT
GOING TO

5781
04:13:09,360 --> 04:13:10,920
COMMENT ON REGULATORY PATHWAY

5782
04:13:10,920 --> 04:13:11,800
BECAUSE I HAVE AN ENTIRE

5783
04:13:11,800 --> 04:13:12,960
PRESENTATION TO TALK ABOUT IT

5784
04:13:12,960 --> 04:13:14,920
BUT I WOULD LIKE TO ASK A

5785
04:13:14,920 --> 04:13:17,400
QUESTION, DR. BARRY. I DO NOT

5786
04:13:17,400 --> 04:13:20,040
WANT TO PUT YOU ON THE SPOT OR

5787
04:13:20,040 --> 04:13:22,360
ANYTHING BUT JUST TO INVITE YOU

5788
04:13:22,360 --> 04:13:25,080
TO DISCUSS THIS WITH ME. SO YOU

5789
04:13:25,080 --> 04:13:29,800
HAVE SHOWN ONE OF YOUR SLIDES

5790
04:13:29,800 --> 04:13:33,040
THAT PATIENTS WHO RESPOND SHOW

5791
04:13:33,040 --> 04:13:34,320
IMPROVEMENTS WITHIN THE FIRST 24

5792
04:13:34,320 --> 04:13:36,200
HOURS. THEN YOU TALK ABOUT

5793
04:13:36,200 --> 04:13:37,880
REGENERATIVE EFFECTS AND

5794
04:13:37,880 --> 04:13:46,520
REPAIRTIVE EFFECTS. SO TELL ME

5795
04:13:46,520 --> 04:13:48,160
ABOUT THE MECHANISTIC

5796
04:13:48,160 --> 04:13:49,200
POSSIBILITY OF A CELL THAT GETS

5797
04:13:49,200 --> 04:13:56,560
INTO INTERARTICULAR JOINT TO

5798
04:13:56,560 --> 04:13:59,560
DIFFERENTIATE OR BECOME A CELL

5799
04:13:59,560 --> 04:14:05,280
LOOKS LIKE CELLS IN THAT

5800
04:14:05,280 --> 04:14:07,280
INTERARTERIAL SPACE CONSIDERING

5801
04:14:07,280 --> 04:14:10,120
FOR EXAMPLE A LIFETIME OF

5802
04:14:10,120 --> 04:14:14,560
CHONDROCYTE OR SYNOVIALCYTE

5803
04:14:14,560 --> 04:14:15,880
INJECTING THE CELLS INTO THE

5804
04:14:15,880 --> 04:14:18,200
JOINT, HOW DO YOU EXPLAIN THE

5805
04:14:18,200 --> 04:14:25,120
PEOPLE IMPROVE WITHIN 24 HOURS? 

5806
04:14:25,120 --> 04:14:26,800
I WILL GIVE YOU CONTEXT. YOU ARE

5807
04:14:26,800 --> 04:14:30,640
NOT PROBABLY THE FIRST TALKING

5808
04:14:30,640 --> 04:14:32,400
ABOUT IMPROVEMENTS AND I HAVE

5809
04:14:32,400 --> 04:14:36,040
SEEN DIFFERENT OPINIONS ONE

5810
04:14:36,040 --> 04:14:37,120
POSSIBILITY IS THESE CELLS ARE

5811
04:14:37,120 --> 04:14:43,400
JUST GOLD, THEY DO MAGIC THERE. 

5812
04:14:43,400 --> 04:14:46,480
SOME ARE SAYING YOU HAVE AN

5813
04:14:46,480 --> 04:14:47,920
OSTEO ARTHRITIC JOINT. WHATEVER

5814
04:14:47,920 --> 04:14:49,760
YOU INJECT THERE, THE JOINT IS

5815
04:14:49,760 --> 04:14:52,680
THE SIZE OF THE DEGENERATIVE

5816
04:14:52,680 --> 04:14:54,880
ALSO MAL ALIGNED SOD YOU GET

5817
04:14:54,880 --> 04:14:57,200
VOLUME, YOU CHANGE THE THE MAL

5818
04:14:57,200 --> 04:14:58,760
ALIGNMENT A LITTLE BIT, YOU

5819
04:14:58,760 --> 04:15:00,640
REBALANCE IT SO PEOPLE MAY FEEL

5820
04:15:00,640 --> 04:15:02,440
BETTER. THEN THERE IS ALWAYS

5821
04:15:02,440 --> 04:15:03,400
PLACEBO EFFECT IN

5822
04:15:03,400 --> 04:15:06,520
OSTEOARTHRITIS.  WHEN TALKING

5823
04:15:06,520 --> 04:15:09,640
ABOUT UNCONTROLLED SITUATIONS.

5824
04:15:09,640 --> 04:15:12,800
SO MAYBE JUST DISCUSS THIS IF

5825
04:15:12,800 --> 04:15:16,000
YOU COULD THE OBSERVATION OF THE

5826
04:15:16,000 --> 04:15:20,520
EARLY RAPID RESPONSE

5827
04:15:20,520 --> 04:15:23,560
>>I THINK IT IS VERY
IMPORTANT

5828
04:15:23,560 --> 04:15:28,040
TO CULTURE WHEN WE REPORT

5829
04:15:28,040 --> 04:15:29,920
RESULTS VARIOUS STAGES OF TRIAL,

5830
04:15:29,920 --> 04:15:32,120
THEY MEAN A LOT.  RAPID RESPONSE

5831
04:15:32,120 --> 04:15:33,920
OR IMPROVED RESPONSE IN PATIENTS

5832
04:15:33,920 --> 04:15:37,040
MAYBE A PLACEBO EFFECT BECAUSE

5833
04:15:37,040 --> 04:15:39,240
THESE ARE OPEN LABEL STUD STUDYU

5834
04:15:39,240 --> 04:15:40,840
CAN KNOW WHAT IT IS LIKE IF

5835
04:15:40,840 --> 04:15:42,080
PATIENT RECEIVES A STEM CELL

5836
04:15:42,080 --> 04:15:43,360
TREATMENT AND KNOW THEY HAVE

5837
04:15:43,360 --> 04:15:45,480
RECEIVED A TREATMENT, THERE IS A

5838
04:15:45,480 --> 04:15:47,480
REASONABLE PROBABILITY THERE IS

5839
04:15:47,480 --> 04:15:48,720
A STRONG PLACEBO AFFECT. IF

5840
04:15:48,720 --> 04:15:51,480
THERE IS A PAIN RESPONSE,

5841
04:15:51,480 --> 04:15:53,320
FUNCTIONAL RESPONSE EARLY AND

5842
04:15:53,320 --> 04:15:56,160
BIOLOGICAL RATIONALE IT IS TO DO

5843
04:15:56,160 --> 04:15:57,800
PROBABLY WITH THE UPREGULATION

5844
04:15:57,800 --> 04:15:59,800
OF ANTI-INFLAMMATORY CYTOKINES

5845
04:15:59,800 --> 04:16:01,680
BY THE CELLS ONCE DELIVERED TO

5846
04:16:01,680 --> 04:16:04,880
THE JOINT, WE HAVE SEEN THAT IN

5847
04:16:04,880 --> 04:16:06,760
THE DIFFERENT STUDIES WE HAVE

5848
04:16:06,760 --> 04:16:12,920
DONE. SO COULD BE CELLS ARE

5849
04:16:12,920 --> 04:16:14,240
HAVING SHORT TERM

5850
04:16:14,240 --> 04:16:16,160
ANTI-INFLAMMATORY EFFECT ON OA

5851
04:16:16,160 --> 04:16:18,280
ENVIRONMENT THAT MAY LEADS TO

5852
04:16:18,280 --> 04:16:19,440
POSITIVE PAIN RESPONSE. IN TERMS

5853
04:16:19,440 --> 04:16:27,920
OF LONGER TERM OUTCOME,

5854
04:16:27,920 --> 04:16:29,920
CONNECTIVE TISSUE PHENOTYPE OR

5855
04:16:29,920 --> 04:16:33,760
CARTILAGE CONTRACYTE. IT IS MORE

5856
04:16:33,760 --> 04:16:36,040
-- CHONDROCYTE, THIS IS

5857
04:16:36,040 --> 04:16:37,840
INFLAMMATORY OR IMMUNE MEDIATED

5858
04:16:37,840 --> 04:16:40,640
EFFECTS BY POLARIZING

5859
04:16:40,640 --> 04:16:42,040
MACROPHAGES TO ANTI-INFLAMMATORY

5860
04:16:42,040 --> 04:16:43,360
STATE OR BY REDUCING THE

5861
04:16:43,360 --> 04:16:49,440
ACTIVATION OF T-CELLS.  IT IS

5862
04:16:49,440 --> 04:16:50,560
LIKELY INTERACTION BETWEEN

5863
04:16:50,560 --> 04:16:54,000
DELIVERED CELLS AND HOST IMMUNE

5864
04:16:54,000 --> 04:16:55,640
CELLS, THAN IT IS

5865
04:16:55,640 --> 04:16:56,920
DIFFERENTIATION OF CELLS TO MAKE

5866
04:16:56,920 --> 04:17:02,360
TISSUE, I DON'T ANY WE KNOW

5867
04:17:02,360 --> 04:17:03,120
ENOUGH TO BE CERTAIN BECAUSE

5868
04:17:03,120 --> 04:17:10,040
THESE ARE HARD ENOUGH TO DO THAT

5869
04:17:10,040 --> 04:17:13,920
IS WHAT I WOULD GUESS AGREE WITH

5870
04:17:13,920 --> 04:17:15,480
YOU, IT IS A CHALLENGE OF

5871
04:17:15,480 --> 04:17:16,560
DEVELOPMENT OF THESE TYPES OF

5872
04:17:16,560 --> 04:17:19,320
PRODUCTS THAT WE DON'T KNOW

5873
04:17:19,320 --> 04:17:22,480
ENOUGH ABOUT WHAT THEY ARE DOING

5874
04:17:22,480 --> 04:17:25,640
IN VIVO AND THERE ARE MANY

5875
04:17:25,640 --> 04:17:31,440
CHALLENGES AND DIFFICULTIES

5876
04:17:31,440 --> 04:17:33,240
STUDIES THESE. THAT IS ONE OF

5877
04:17:33,240 --> 04:17:37,000
THE GAPS IN T FELTED TO TRY TO

5878
04:17:37,000 --> 04:17:41,840
BETTER UNDERSTAND WHAT THEY DO.

5879
04:17:41,840 --> 04:17:42,920
REGENERATIVE ANTI-INFLAMMATORY

5880
04:17:42,920 --> 04:17:44,560
EFFECTS ARE GOING TO BE THERE.

5881
04:17:44,560 --> 04:17:46,600
>>THESE QUESTIONS ARE
CRITICAL

5882
04:17:46,600 --> 04:17:48,160
TO ANSWER OTHERWISE WE WON'T

5883
04:17:48,160 --> 04:17:50,560
MAKE THE PROGRESS NEEDED. ALL

5884
04:17:50,560 --> 04:17:53,240
THE TECHNICAL WILL GISTICAL

5885
04:17:53,240 --> 04:17:55,440
BIOLOGICAL HURDLES THAT YET NEED

5886
04:17:55,440 --> 04:17:57,200
TO BE OVERCOME BEFORE WE CAN

5887
04:17:57,200 --> 04:17:59,080
MOVE FORWARD. WE HAVEN'T DONE A

5888
04:17:59,080 --> 04:18:02,720
GOOD JOB TO DATE. WE NEED TO

5889
04:18:02,720 --> 04:18:05,440
IMPROVE THIS IS ISSUES.  --

5890
04:18:05,440 --> 04:18:06,040
THESE ISSUES.

5891
04:18:06,040 --> 04:18:10,240
>>THANK YOU SO MUCH. TED,
WE

5892
04:18:10,240 --> 04:18:13,640
ARE KIND OF THROUGH THE BREAK

5893
04:18:13,640 --> 04:18:17,280
TIME, ALMOST ON TIME. SHALL WE

5894
04:18:17,280 --> 04:18:19,200
MOVE TO LARISSA'S TALK?

5895
04:18:19,200 --> 04:18:24,400
>>I VOTE TO DO SO.

5896
04:18:24,400 --> 04:18:28,480
>>DR. LARISSA LAPTEVA IS

5897
04:18:28,480 --> 04:18:31,000
ASSOCIATE DIRECTOR DIVISION OF

5898
04:18:31,000 --> 04:18:32,800
CLINICAL EVALUATION PHARMACOLOGY

5899
04:18:32,800 --> 04:18:39,240
AND TOXICOLOGY. FOR CBER. AS U

5900
04:18:39,240 --> 04:18:40,360
YOU HEARD HER LINE OF

5901
04:18:40,360 --> 04:18:42,040
QUESTIONING AND INTRODUCTION SHE

5902
04:18:42,040 --> 04:18:48,160
IS CLINICIAN SCIENTIST. SHE

5903
04:18:48,160 --> 04:18:51,160
CONTINUES TO PRACTICE

5904
04:18:51,160 --> 04:18:52,920
RHEUMATOLOGY AS AN ATTENDING

5905
04:18:52,920 --> 04:18:54,200
PHYSICIAN IN OUTPATIENT

5906
04:18:54,200 --> 04:18:55,200
RHEUMATOLOGY CLINIC NATIONAL

5907
04:18:55,200 --> 04:19:00,680
INSTITUTES OF HEALTH. SHE IS

5908
04:19:00,680 --> 04:19:01,560
CONTRIBUTING HER TIME AND

5909
04:19:01,560 --> 04:19:05,280
EXPERTISE TO TALK TO US AN

5910
04:19:05,280 --> 04:19:06,200
REGULATORY CONSIDERATIONS FOR

5911
04:19:06,200 --> 04:19:07,960
DEVELOPMENT OF BIOLOGICAL

5912
04:19:07,960 --> 04:19:08,960
PRODUCTS TO TREAT

5913
04:19:08,960 --> 04:19:13,880
OSTEOARTHRITIS.

5914
04:19:13,880 --> 04:19:15,280
>>THANK YOU FOR THE NICE

5915
04:19:15,280 --> 04:19:16,240
INTRODUCTION. GOOD AFTERNOON, A

5916
04:19:16,240 --> 04:19:17,800
PLEASURE TO BE PART OF THIS

5917
04:19:17,800 --> 04:19:21,480
ROUND TABLE DISCUSSION AND

5918
04:19:21,480 --> 04:19:23,000
PERSONALLY FOR ME IT IS NICE TO

5919
04:19:23,000 --> 04:19:25,000
COME BACK THE ALMA MATER AND SEE

5920
04:19:25,000 --> 04:19:27,760
FAMILIAR FACES AND ENGAGE IN

5921
04:19:27,760 --> 04:19:29,320
INTERESTING THOUGHT PROVOKING

5922
04:19:29,320 --> 04:19:34,440
CONVERSATIONS.  SO I ASKED LAST

5923
04:19:34,440 --> 04:19:36,160
MONDAY TO GIVE ADDITIONAL TIME

5924
04:19:36,160 --> 04:19:40,880
BECAUSE I REALIZE THAT ONE OF

5925
04:19:40,880 --> 04:19:44,200
THE GAPS, THAT'S WHAT I THOUGHT

5926
04:19:44,200 --> 04:19:48,280
AFTER READING BACKGROUND

5927
04:19:48,280 --> 04:19:50,520
MATERIALS THAT MAYBE PRESENT IN

5928
04:19:50,520 --> 04:19:52,280
THE FIELD SCIENTIFIC AUDIENCE

5929
04:19:52,280 --> 04:19:53,640
AND INVESTIGATORS PARTICULARLY

5930
04:19:53,640 --> 04:20:03,480
IN MANY CLINICIANS I THOUGHT I

5931
04:20:03,480 --> 04:20:06,520
WOULD MAYBE EXPLAIN THIS A

5932
04:20:06,520 --> 04:20:11,040
LITTLE AND DO MULTI-TASKING, GET

5933
04:20:11,040 --> 04:20:14,320
THE PRESENTATION IN THE I WILL

5934
04:20:14,320 --> 04:20:15,960
HIGHLIGHT REGULATORY ASPECTS

5935
04:20:15,960 --> 04:20:17,200
PERTINENT TO DEVELOPMENT OF DRUG

5936
04:20:17,200 --> 04:20:22,080
AND BIOLOGICAL PRODUCTS FOR

5937
04:20:22,080 --> 04:20:26,080
OSTEOARTHRITIS AND FDA

5938
04:20:26,080 --> 04:20:34,920
PERSPECTIVE ON THIS TOPIC.  AS

5939
04:20:34,920 --> 04:20:36,720
YOU CAN SEE FDA REVIEWING

5940
04:20:36,720 --> 04:20:38,400
REGULAR RATORY WORK ACCOMPLISHED

5941
04:20:38,400 --> 04:20:40,360
THROUGH FUNCTIONING OF DIFFERENT

5942
04:20:40,360 --> 04:20:42,400
CENTERS, I COME FROM CENTER FOR

5943
04:20:42,400 --> 04:20:44,400
BIOLOGIC AND OFFICE OF TISSUE

5944
04:20:44,400 --> 04:20:49,280
AND ADVANCE THERAPY MY

5945
04:20:49,280 --> 04:20:49,840
PRESENTATION WILL BE WILL BE

5946
04:20:49,840 --> 04:20:51,160
FOCUSING ON A NUMBER OF

5947
04:20:51,160 --> 04:20:53,360
BIOLOGICAL PRODUCTS THAT THE

5948
04:20:53,360 --> 04:20:58,920
OFFICE REGULATES WHICH YOU CAN

5949
04:20:58,920 --> 04:21:04,960
SEE HERE. XENOTRANSPLANTATION,

5950
04:21:04,960 --> 04:21:07,200
THERAPEUTIC VACCINES TISSUE

5951
04:21:07,200 --> 04:21:11,200
ENGINEER PRODUCTS, THE NUMBER OF

5952
04:21:11,200 --> 04:21:12,760
OTHERS. BECAUSE WE ARE TALKING

5953
04:21:12,760 --> 04:21:15,080
REGENERATIVE MEDICINE AND

5954
04:21:15,080 --> 04:21:16,960
THERAPIES, I WOULD LIKE TO

5955
04:21:16,960 --> 04:21:17,920
MENTION DEFINITION OF

5956
04:21:17,920 --> 04:21:22,160
REGENERATIVE MEDICINE THERAPIES 

5957
04:21:22,160 --> 04:21:25,120
THE WAY IT WAS WRITTEN IN 21ST

5958
04:21:25,120 --> 04:21:27,240
SENTRY CURES ACT, THAT IS WHAT

5959
04:21:27,240 --> 04:21:31,960
FDA CONSIDERS REGENERATIVE

5960
04:21:31,960 --> 04:21:35,360
THERAPY. LIB FOR A MINUTE AS I

5961
04:21:35,360 --> 04:21:37,640
EXPLAIN. FDA IS A REGULATORY

5962
04:21:37,640 --> 04:21:39,080
AGENCY, EVERYBODY KNOWS, QUITE

5963
04:21:39,080 --> 04:21:43,240
WELL, AND REGULATION AND RULES

5964
04:21:43,240 --> 04:21:48,120
ARE EXTENSIONS OF LAWS.  THE TWO

5965
04:21:48,120 --> 04:21:57,720
MAIN LAWS PUBLIC SERVICE ACT

5966
04:21:57,720 --> 04:22:00,160
BIOLOGICS DRUG DEVELOPMENT IS A

5967
04:22:00,160 --> 04:22:01,960
BUSINESS, IS HIGHLY DEPENDENT ON

5968
04:22:01,960 --> 04:22:05,120
INNOVATION AND IT HAS TO GO IN

5969
04:22:05,120 --> 04:22:06,320
PARALLEL WITH ADVANCEMENT IN

5970
04:22:06,320 --> 04:22:09,800
SCIENCE AND TECHNOLO TECHNOLOGYS

5971
04:22:09,800 --> 04:22:12,800
MEDICAL PRODUCT DEVELOPMENT

5972
04:22:12,800 --> 04:22:13,800
REFLECTIVE AND CONDUCIVE OF

5973
04:22:13,800 --> 04:22:18,240
THESE ADVANCEMENTS. SO TWO MAIN

5974
04:22:18,240 --> 04:22:20,960
ONES I NAMED GET UPDATED EVERY

5975
04:22:20,960 --> 04:22:22,640
FIVE YEARS THROUGH

5976
04:22:22,640 --> 04:22:24,000
RE-AUTHORIZATION OF THE LAW

5977
04:22:24,000 --> 04:22:25,440
CALLED PRESCRIPTION DRUG USER

5978
04:22:25,440 --> 04:22:29,160
FEE ACT TO REFLECT FIELD

5979
04:22:29,160 --> 04:22:30,320
ADVANCEMENTS AND MEET THE NEEDS

5980
04:22:30,320 --> 04:22:31,840
OF DAY AND SOMETIMES NEW LAWS

5981
04:22:31,840 --> 04:22:33,080
ARE WRITTEN AND PASSED

5982
04:22:33,080 --> 04:22:35,600
SEPARATELY AS WAS THE CASE WITH

5983
04:22:35,600 --> 04:22:38,440
21ST CENTURY CURES ACT, WHICH

5984
04:22:38,440 --> 04:22:43,280
WAS PASSED END OF 2017 AND STUM

5985
04:22:43,280 --> 04:22:45,680
LATE REGENERAL RATIVE THERAPIES.

5986
04:22:45,680 --> 04:22:48,840
THAT LAW DEFINED AS CELLULAR

5987
04:22:48,840 --> 04:22:51,040
THERAPIES, THERAPEUTIC TISSUE

5988
04:22:51,040 --> 04:22:52,720
ENGINEERING PRODUCTS HUMAN CELL

5989
04:22:52,720 --> 04:22:54,240
TISSUE PRODUCTS AND COMBINATION

5990
04:22:54,240 --> 04:22:58,880
OF THE ABOVE, IN P ESSENCE ALL

5991
04:22:58,880 --> 04:23:00,320
PRODUCTS THAT SUSTAIN EFFECT

5992
04:23:00,320 --> 04:23:05,720
HUMAN CELLS AND TISSUE. LAWS

5993
04:23:05,720 --> 04:23:06,760
ANDRAL RATIONS ARE BRING BY

5994
04:23:06,760 --> 04:23:11,560
LAWYERS AND POLICY MAKERS DRUG

5995
04:23:11,560 --> 04:23:13,800
DEVELOPMENT DONE BY SCIENTISTS

5996
04:23:13,800 --> 04:23:16,040
SO FDA FINDS ITSELF IN A

5997
04:23:16,040 --> 04:23:19,280
POSITION TO EXPLAIN TECHNICAL

5998
04:23:19,280 --> 04:23:22,480
EXPERTS HOW TO APPLY DIFFERENT

5999
04:23:22,480 --> 04:23:26,840
REGULATIONS. WE DO IT BY

6000
04:23:26,840 --> 04:23:29,040
PUBLISHING GUIDANCE, IT IS A

6001
04:23:29,040 --> 04:23:35,640
PUBLIC PROCESS. THAT IS HOW WE

6002
04:23:35,640 --> 04:23:37,200
INTERPRET WHICH PRODUCTSES TO

6003
04:23:37,200 --> 04:23:40,720
CALL AND WHICH NOT TO CALL. 

6004
04:23:40,720 --> 04:23:42,080
REGENERATIVE MEDICINE. I WILL

6005
04:23:42,080 --> 04:23:52,640
SHOW YOU GUIDANCE ON LAST SLIDE 

6006
04:23:55,000 --> 04:23:56,080
ALTHOUGH WE SEE DIFFERENT

6007
04:23:56,080 --> 04:23:58,040
PRODUCT PROGRAMS, THE LARGEST

6008
04:23:58,040 --> 04:24:01,360
BULK OFVATIONAL NEW DRUG

6009
04:24:01,360 --> 04:24:03,120
APPLICATIONS EACH IND

6010
04:24:03,120 --> 04:24:04,120
APPLICATION IS A SEPARATE

6011
04:24:04,120 --> 04:24:06,600
PRODUCT PROGRAM. SO THE LARGEST

6012
04:24:06,600 --> 04:24:07,880
WE SEE COMES FOR CELLULAR AN

6013
04:24:07,880 --> 04:24:10,320
GENE THERAPIES.  WE USED TO SEE

6014
04:24:10,320 --> 04:24:11,880
MORE CELL THERAPIES COMPARED TO

6015
04:24:11,880 --> 04:24:14,560
GENE THERAPY BUT THE TRENDS

6016
04:24:14,560 --> 04:24:17,840
REVERSED IN 2016 ON THE SLIDE,

6017
04:24:17,840 --> 04:24:19,520
AND THE PEAK APPLICATION FOR

6018
04:24:19,520 --> 04:24:23,960
CELLULAR THERAPIES OBSERVED IN

6019
04:24:23,960 --> 04:24:27,880
YEAR 2020. WAS RELATED TO

6020
04:24:27,880 --> 04:24:32,440
COVID-19 PANDEMIC. HERE YOU SEE

6021
04:24:32,440 --> 04:24:33,280
IMPORTANT CONSIDERATIONS FOR

6022
04:24:33,280 --> 04:24:34,400
DEVELOPMENT OF CELLULAR

6023
04:24:34,400 --> 04:24:37,840
THERAPIES AND GENE THERAPIES

6024
04:24:37,840 --> 04:24:39,880
APPLY REGENERATIVE MEDICINES AND

6025
04:24:39,880 --> 04:24:44,320
THEY OBVIOUSLY APPLY TO PRODUCTS

6026
04:24:44,320 --> 04:24:47,320
DEVELOPED FOR OSTEOARTHRITIS.

6027
04:24:47,320 --> 04:24:49,760
ADVANCE THERAPY PRODUCTS ARE

6028
04:24:49,760 --> 04:24:51,160
EXPECTED TO HAVE PROLONGED

6029
04:24:51,160 --> 04:24:54,040
THERAPEUTIC EFFECTS WHICH FROM

6030
04:24:54,040 --> 04:24:55,240
PRODUCT DEVELOPMENT RESULTS IN

6031
04:24:55,240 --> 04:24:57,000
NEED FOR LONG TERM FOLLOW-UP FOR

6032
04:24:57,000 --> 04:25:00,640
BOTH EFFICACY AND SAFETY. AS

6033
04:25:00,640 --> 04:25:02,440
ALLUDED AND DISCUSSED MENTIONED

6034
04:25:02,440 --> 04:25:05,200
BY MANY PRESENTERS TODAY, THERE

6035
04:25:05,200 --> 04:25:06,520
ARE CHALLENGE WITH ASSESSING

6036
04:25:06,520 --> 04:25:09,680
PRECISE MECHANISM OF ACTION. FOR

6037
04:25:09,680 --> 04:25:16,120
THESE PRODUCTS. YOU SEE OUTGAS

6038
04:25:16,120 --> 04:25:19,160
THERAPIES.  NOT ALLOGENEIC BUT

6039
04:25:19,160 --> 04:25:21,120
AUTOLOGOUS.  EVALUATING BECAUSE

6040
04:25:21,120 --> 04:25:24,960
IT IS IMPORTANT TO SET UP

6041
04:25:24,960 --> 04:25:27,320
ESTABLISH APPROPRIATE DOSE OF

6042
04:25:27,320 --> 04:25:30,040
PRODUCT WHEN GIVEN TO PEOPLE SO

6043
04:25:30,040 --> 04:25:31,800
EVALUATING POTENCY IN THOSE

6044
04:25:31,800 --> 04:25:33,480
MAYBE DIFFICULT. WITH CELL

6045
04:25:33,480 --> 04:25:35,800
THERAPIES AS WELL AS GENE

6046
04:25:35,800 --> 04:25:42,480
THERAPIES, WITH CELL THERAPIES,

6047
04:25:42,480 --> 04:25:44,520
IT IS CHALLENGING TO PREDICT HOW

6048
04:25:44,520 --> 04:25:47,440
CELL POPULATION MAY HAVES IN

6049
04:25:47,440 --> 04:25:50,400
VIVO WHETHER -- BEHAVIOR IN VIVO

6050
04:25:50,400 --> 04:25:53,520
WHETHER IT EXPANDS CELLULAR

6051
04:25:53,520 --> 04:25:55,560
VIABILITY AND THAT BECOMES

6052
04:25:55,560 --> 04:25:57,000
IMPORTANT HERE. MANY CHALLENGES

6053
04:25:57,000 --> 04:25:59,200
AS WAS DISCUSSED BEFORE BUT THE

6054
04:25:59,200 --> 04:26:01,320
PRESENCE OF CHALLENGES DOES NOT

6055
04:26:01,320 --> 04:26:02,720
REALLY REASON -- IS NOT A REASON

6056
04:26:02,720 --> 04:26:05,480
NOT TO DO ADEQUATE INVESTIGATION

6057
04:26:05,480 --> 04:26:06,600
TO BETTER UNDERSTAND WHAT THE

6058
04:26:06,600 --> 04:26:12,000
PRODUCT DOES, WHERE IT GOES, HOW

6059
04:26:12,000 --> 04:26:22,320
GENE THERAPIES ARE DISTRIBUTED. 

6060
04:26:22,320 --> 04:26:24,840
WE ASK WHEN PEOPLE COULD SHOW

6061
04:26:24,840 --> 04:26:27,280
DIFFERENT MECHANISMS OF ACTIONS

6062
04:26:27,280 --> 04:26:29,280
THAT HAVE BEEN SEEN IN SIMILAR

6063
04:26:29,280 --> 04:26:32,240
PRODUCTS IN BODY OF LITERATURE,

6064
04:26:32,240 --> 04:26:38,200
SOME REMOTELY, WE TRIED TO

6065
04:26:38,200 --> 04:26:39,840
EXPLAIN VERY IMPORTANT. TO IN

6066
04:26:39,840 --> 04:26:46,680
FACT DEMONSTRATE WHAT IS THE

6067
04:26:46,680 --> 04:26:47,480
PRODUCT DOES IN PATIENT

6068
04:26:47,480 --> 04:26:48,880
POPULATION, WHAT IS MECHANISM OF

6069
04:26:48,880 --> 04:26:52,440
ACTION AND IF THIS IS A PRODUCT

6070
04:26:52,440 --> 04:26:55,440
THAT CONTAINS CELLS THAT IS

6071
04:26:55,440 --> 04:26:58,280
THERE TO PROVIDE

6072
04:26:58,280 --> 04:27:00,360
ANTI-INFLAMMATORY RESPONSES FOR

6073
04:27:00,360 --> 04:27:01,480
CHONDROCYTES THAT MECHANISM OF

6074
04:27:01,480 --> 04:27:04,920
ACTION NEEDS TO BE DEMONSTRATED.

6075
04:27:04,920 --> 04:27:08,120
SO INVESTIGATORS NEED TO HAVE A

6076
04:27:08,120 --> 04:27:11,200
PLAN IN PLACE STARTING THOSE HOW

6077
04:27:11,200 --> 04:27:12,400
SPECIFIC PRODUCT ADMINISTRATION

6078
04:27:12,400 --> 04:27:14,520
MAYBE SUPPORTED BY A

6079
04:27:14,520 --> 04:27:18,040
PRE-CLINICAL PROGRAM. CELLULAR

6080
04:27:18,040 --> 04:27:19,800
-- BY DISTRIBUTION DEPEND ON

6081
04:27:19,800 --> 04:27:22,480
MANY FACTORS INCLUDING IN SITU

6082
04:27:22,480 --> 04:27:25,720
MICROENVIRONMENT AN DISEASE

6083
04:27:25,720 --> 04:27:26,760
STATE, COMMUNICATION AND NUMBER

6084
04:27:26,760 --> 04:27:29,960
OF OTHER FACTORS AND WE EXPECT

6085
04:27:29,960 --> 04:27:33,640
STUDIES TO BE DONE TO UNDERSTAND

6086
04:27:33,640 --> 04:27:36,320
WHERE THE PRODUCT GOES. I DID

6087
04:27:36,320 --> 04:27:37,440
PUT A LINK TO THE

6088
04:27:37,440 --> 04:27:38,160
RECOMMENDATIONS AND

6089
04:27:38,160 --> 04:27:39,160
BIODISTRIBUTION STUDIES HERE

6090
04:27:39,160 --> 04:27:40,920
FROM THE INTERNATIONAL

6091
04:27:40,920 --> 04:27:42,480
PHARMACEUTICAL REGULATORS

6092
04:27:42,480 --> 04:27:45,440
PROGRAM. YOU SEE AT THE BOTTOM

6093
04:27:45,440 --> 04:27:47,600
OF THE SLIDE. FOR PART OF THE

6094
04:27:47,600 --> 04:27:49,040
WORKING GROUP WRITING THIS PAPER

6095
04:27:49,040 --> 04:27:50,960
SO WE CONFORM TO THE

6096
04:27:50,960 --> 04:27:54,160
RECOMMENDATIONS PRESENTED THERE 

6097
04:27:54,160 --> 04:27:56,320
IMMUNOGENICITY IS AN ISSUE WITH

6098
04:27:56,320 --> 04:27:57,240
BIOLOGICAL PRODUCT IN GENERAL

6099
04:27:57,240 --> 04:28:00,080
AND CELL AND GENE THERAPIES IN

6100
04:28:00,080 --> 04:28:01,840
PARTICULAR. TYPICALLY

6101
04:28:01,840 --> 04:28:03,280
IMMUNOGENICITY IS SOMETHING WE

6102
04:28:03,280 --> 04:28:06,280
ASK PRODUCT DEVELOPERS TO

6103
04:28:06,280 --> 04:28:08,760
ADDRESS. IN BASIC PROCEDURES FOR

6104
04:28:08,760 --> 04:28:10,320
PRODUCT DELIVERY IS ANOTHER

6105
04:28:10,320 --> 04:28:13,800
IMPORTANT ASPECT OF DEVELOPMENT,

6106
04:28:13,800 --> 04:28:15,360
BESIDES SAFE ADMINISTRATION OF

6107
04:28:15,360 --> 04:28:17,560
PRODUCT TO TENDED ANATOMICAL

6108
04:28:17,560 --> 04:28:19,360
SITE IT IS IMPORTANT TO ENSURE

6109
04:28:19,360 --> 04:28:21,120
THE PRODUCT IS IN FACT

6110
04:28:21,120 --> 04:28:23,040
COMPATIBLE WITH THE DEVICE USED

6111
04:28:23,040 --> 04:28:25,840
FOR ADMINISTRATION. WHATEVER

6112
04:28:25,840 --> 04:28:28,200
PRODUCT MATERIAL IS DELIVERED

6113
04:28:28,200 --> 04:28:30,520
WHEN IT FLOWS THROUGH THE DEVICE

6114
04:28:30,520 --> 04:28:32,160
SHOULD REMAIN VIABLE WHEN IT

6115
04:28:32,160 --> 04:28:40,280
GETS TO THE TARGET TISSUE. SO

6116
04:28:40,280 --> 04:28:42,040
FOR MANY DISEASE POPULATIONS IN

6117
04:28:42,040 --> 04:28:44,160
OSTEOARTHRITIS IS NO EXCEPTION,

6118
04:28:44,160 --> 04:28:45,600
WHEN A CELL OR GENE THERAPY

6119
04:28:45,600 --> 04:28:49,400
PRODUCT IS BEING DEVELOPED, DOSE

6120
04:28:49,400 --> 04:28:50,480
LIMITING TOXICITY ARE NOT

6121
04:28:50,480 --> 04:28:51,800
READILY OBSERVABLE EARLY IN

6122
04:28:51,800 --> 04:28:54,680
DEVELOPMENT SO THE DURATION OF

6123
04:28:54,680 --> 04:28:56,200
FOLLOW-UP FOR THE PRODUCTS THAT

6124
04:28:56,200 --> 04:28:58,240
WE ARE DEALING WITH MAY TAKE

6125
04:28:58,240 --> 04:29:01,560
LONGER COMPARED FOR EXAMPLE THAN

6126
04:29:01,560 --> 04:29:04,040
WITH DRUGS, MAY TAKE LONGER EVEN

6127
04:29:04,040 --> 04:29:06,880
INITIAL FIRST IN HUMAN STUDIES

6128
04:29:06,880 --> 04:29:08,680
BUT THIS SHOULD BE TAILORED TO

6129
04:29:08,680 --> 04:29:11,200
INDIVIDUAL PRODUCTS. WE REQUEST

6130
04:29:11,200 --> 04:29:14,160
CAREFUL PRODUCT ADMINISTRATION

6131
04:29:14,160 --> 04:29:16,520
AND INVESTIGATORS SHOULD

6132
04:29:16,520 --> 04:29:18,280
REMEMBER TO MONITOR WHAT

6133
04:29:18,280 --> 04:29:20,600
IMMEDIATE REACTIONS AND TO HAVE

6134
04:29:20,600 --> 04:29:21,680
STAGGERED ADMINISTRATION AND

6135
04:29:21,680 --> 04:29:24,600
STOPPING CRITERIA IN THE

6136
04:29:24,600 --> 04:29:26,320
PROTOCOL FOR BOTH INDIVIDUAL

6137
04:29:26,320 --> 04:29:29,440
SUBJECTS IN THE ENTIRE STUDY,

6138
04:29:29,440 --> 04:29:31,280
AND I KNOW NUMBER OF FOLKS FROM

6139
04:29:31,280 --> 04:29:33,680
THE EXTRAMURAL PROGRAM IS

6140
04:29:33,680 --> 04:29:37,600
PARTICIPATING IN THIS ROUND

6141
04:29:37,600 --> 04:29:42,320
TABLE, I KNOW YOU GUYS HELP

6142
04:29:42,320 --> 04:29:44,200
FACILITATE PROTOCOL DEVELOPMENT,

6143
04:29:44,200 --> 04:29:46,720
YOU SEE PROTOCOLS SO IF YOU SEE

6144
04:29:46,720 --> 04:29:48,960
PROTOCOL THAT LACKS STOPPING

6145
04:29:48,960 --> 04:29:50,280
CRITERIA FOR THE TOXICITY

6146
04:29:50,280 --> 04:29:51,720
PARTICULARLY WHEN IT IS FIRST IN

6147
04:29:51,720 --> 04:29:54,760
HUMAN STUDY, AND THE CRITERIA

6148
04:29:54,760 --> 04:29:55,480
SHOULD BE BOTH INDIVIDUAL

6149
04:29:55,480 --> 04:29:59,040
SUBJECTS AND THE ENTIRE STUDY,

6150
04:29:59,040 --> 04:30:02,360
IT MAY BE GOOD AND YOU PROBABLY

6151
04:30:02,360 --> 04:30:03,640
SERVE TO PATIENT SAFETY, GO BACK

6152
04:30:03,640 --> 04:30:06,840
TO THE INVESTIGATOR AND ASK THEM

6153
04:30:06,840 --> 04:30:08,440
TO REVISE PROTOCOL, IF YOU DON'T

6154
04:30:08,440 --> 04:30:10,480
DO THAT WE HAVE TO DO IT WHEN IT

6155
04:30:10,480 --> 04:30:12,560
COMES -- WHEN THE PROTOCOL COMES

6156
04:30:12,560 --> 04:30:17,680
TO US. WE HAVE SEEN NEW

6157
04:30:17,680 --> 04:30:18,840
OSTEOARTHRITIS PROGRAMS WITH

6158
04:30:18,840 --> 04:30:19,960
CELLULAR PRODUCTS PAIN AND

6159
04:30:19,960 --> 04:30:23,440
SWELLING AND REACTIVE SINUVITIS

6160
04:30:23,440 --> 04:30:25,200
WAS OBSERVED IN MAJORITY OF

6161
04:30:25,200 --> 04:30:26,360
PATIENTS WITH THE

6162
04:30:26,360 --> 04:30:28,080
INVESTIGATIONAL PRODUCT SO THESE

6163
04:30:28,080 --> 04:30:30,520
OCCURRENCES ARE NOT THEORETICAL,

6164
04:30:30,520 --> 04:30:32,560
WE HAVE SEEN BAD THINGS AND

6165
04:30:32,560 --> 04:30:34,400
THEREFORE IT IS IMPORTANT TO

6166
04:30:34,400 --> 04:30:37,440
PROCEED CAUTIOUSLY AND CAREFULLY

6167
04:30:37,440 --> 04:30:41,240
PARTICULARLY WHEN DEALING WITH

6168
04:30:41,240 --> 04:30:43,240
NOVEL PRODUCT. DURATION OF

6169
04:30:43,240 --> 04:30:45,880
MONITORING OFTEN DEPENDS ON

6170
04:30:45,880 --> 04:30:47,880
ANTICIPATED PRODUCT EFFECT AND

6171
04:30:47,880 --> 04:30:51,720
PRODUCTS WHERE REGENERATIVE

6172
04:30:51,720 --> 04:30:54,720
EFFECT OR IN VIVO CELLULAR

6173
04:30:54,720 --> 04:30:55,800
DIFFERENTIATION OR ENGRAFTMENT.

6174
04:30:55,800 --> 04:30:58,400
WE HAVE SEEN PRODUCTS WHERE

6175
04:30:58,400 --> 04:31:02,600
ENGRAFTMENT IS EXPECTED. WE SEE

6176
04:31:02,600 --> 04:31:04,480
MONITORING AND WE RECOMMEND

6177
04:31:04,480 --> 04:31:06,560
MONITOR FOR AT LEAST ONE YEAR OR

6178
04:31:06,560 --> 04:31:10,840
LONGER BECAUSE IF WE ARE TALKING

6179
04:31:10,840 --> 04:31:12,720
ABOUT REGENERATIVE THERAPY YOU

6180
04:31:12,720 --> 04:31:14,960
SEE DURABILITY OF THE EFFECT AND

6181
04:31:14,960 --> 04:31:15,680
CONSIDERATION SIS OF THE EFFECT

6182
04:31:15,680 --> 04:31:20,320
OVER TIME.  IN TERMS OF SAFETY

6183
04:31:20,320 --> 04:31:21,800
LONG TERM WE WORRY ABOUT THINGS

6184
04:31:21,800 --> 04:31:24,320
LIKE ECTOPIC TISSUE FORMATION.

6185
04:31:24,320 --> 04:31:26,760
IF CELLULAR DIFFERENTIATION DOES

6186
04:31:26,760 --> 04:31:31,520
NOT GO IN THE INTENDED DIRECTION

6187
04:31:31,520 --> 04:31:34,760
AND FOLKS WHO WORK WITH CELL

6188
04:31:34,760 --> 04:31:35,880
CULTURE KNOW IF YOU INCREASE

6189
04:31:35,880 --> 04:31:38,000
NUMBER OF PASSAGES IN CULTURE

6190
04:31:38,000 --> 04:31:40,640
THAT INTRODUCES GENETIC

6191
04:31:40,640 --> 04:31:42,400
INSTABILITY SO PRODUCT

6192
04:31:42,400 --> 04:31:44,320
CHARACTERIZATION AGAIN WAS

6193
04:31:44,320 --> 04:31:46,520
DISCUSSED BEFORE TODAY. AND

6194
04:31:46,520 --> 04:31:50,880
DURING THE ROUND TABLE, PRODUCT

6195
04:31:50,880 --> 04:31:52,800
CHARACTERIZATION AND APPROPRIATE

6196
04:31:52,800 --> 04:31:54,400
PROTOCOL ARE EXTREMELY IMPORTANT

6197
04:31:54,400 --> 04:31:55,640
IN UNDERSTANDING WHAT THE

6198
04:31:55,640 --> 04:31:58,760
PRODUCT WILL EVENTUALLY DO IN --

6199
04:31:58,760 --> 04:32:01,960
WHEN INTRODUCED TO PATIENTS. A

6200
04:32:01,960 --> 04:32:04,160
POSSIBILITY OF ACCELERATION OF

6201
04:32:04,160 --> 04:32:05,480
CARTILAGE DEGRADATION. WHICH IS

6202
04:32:05,480 --> 04:32:06,960
AN EFFECT THAT IS COMPLETELY

6203
04:32:06,960 --> 04:32:08,840
OPPOSITE WHAT WE ARE TRYING TO

6204
04:32:08,840 --> 04:32:11,800
DO BUT THIS IS AGAIN NOT AN

6205
04:32:11,800 --> 04:32:14,360
UNHEARD OF SITUATION AND THIS

6206
04:32:14,360 --> 04:32:16,040
SOMETHING TO KEEP IN THE BACK OF

6207
04:32:16,040 --> 04:32:18,920
OUR MINDS. TUMORIGENITICITY IS

6208
04:32:18,920 --> 04:32:21,240
ALSO AN ISSUE WITH CELL PRODUCTS

6209
04:32:21,240 --> 04:32:23,280
INSERTIONAL MUTAGENESIS WOULD BE

6210
04:32:23,280 --> 04:32:25,760
SOMETHING THAT WE ARE LOOKING

6211
04:32:25,760 --> 04:32:27,720
NOT TO HAVE IN GENE THERAPY

6212
04:32:27,720 --> 04:32:30,640
PRODUCTS.  SPECIFICALLY FOR GENE

6213
04:32:30,640 --> 04:32:31,720
THERAPIES FDA RECOMMENDATIONS

6214
04:32:31,720 --> 04:32:34,440
FOR LONG TERM FOLLOW-UP AFTER

6215
04:32:34,440 --> 04:32:35,560
TREATMENT WITH GENE THERAPIES

6216
04:32:35,560 --> 04:32:38,320
AND THE DURATION OF FOLLOW-UP

6217
04:32:38,320 --> 04:32:41,400
DEPENDS ON THE VIRAL VECTOR

6218
04:32:41,400 --> 04:32:43,480
CONSTRUCT IN ANY ANTICIPATED

6219
04:32:43,480 --> 04:32:45,080
POTENTIAL FOR INSERTIONAL

6220
04:32:45,080 --> 04:32:52,800
MUTAGENESIS.  HERE ARE SOME

6221
04:32:52,800 --> 04:32:54,240
EXAMPLES OF PRODUCT PROGRAMS AND

6222
04:32:54,240 --> 04:32:59,280
TYPES OF PRODUCTS WE SEE FOR OA

6223
04:32:59,280 --> 04:33:00,800
DEVELOPMENT, BOTH CELLULAR AND

6224
04:33:00,800 --> 04:33:04,280
GENE THERAPIES FOR

6225
04:33:04,280 --> 04:33:06,040
OSTEOARTHRITIS AS WAS DISCUSSED

6226
04:33:06,040 --> 04:33:09,160
BEFORE, THEY ARE ALSO NUMBER OF

6227
04:33:09,160 --> 04:33:10,400
AUTOLOGOUS CARTILAGE

6228
04:33:10,400 --> 04:33:12,600
IMPLANTATION PRODUCTS THAT ARE

6229
04:33:12,600 --> 04:33:15,600
EITHER APPROVED BEING DEVELOPED

6230
04:33:15,600 --> 04:33:19,080
IN THE PIPELINE BUT THOSE ARE

6231
04:33:19,080 --> 04:33:21,920
DEVELOPED NOT NECESSARILY PER SE

6232
04:33:21,920 --> 04:33:22,920
DEVELOPED WITH DISTINCT

6233
04:33:22,920 --> 04:33:25,480
CARTILAGE DEFECT, OSTEOARTHRITIS

6234
04:33:25,480 --> 04:33:30,440
CAN BE PRESENT IN THE JOINT AS

6235
04:33:30,440 --> 04:33:32,040
CO-MORBIDITY SO TO SPEAK BUT

6236
04:33:32,040 --> 04:33:33,160
ESSENTIALLY THESE PRODUCTS ARE

6237
04:33:33,160 --> 04:33:35,240
STILL DEVELOPED FOR DISTINCT

6238
04:33:35,240 --> 04:33:37,800
CARTILAGE DETECTS. WE ALSO SEE A

6239
04:33:37,800 --> 04:33:42,120
NUMBER OF INVESTIGATIONAL DEVICE

6240
04:33:42,120 --> 04:33:44,560
APPLICATIONS. WITH PRODUCTS THAT

6241
04:33:44,560 --> 04:33:47,000
PRODUCE BIOLOGICAL OUTPUT

6242
04:33:47,000 --> 04:33:48,400
PURPORTED TO HAVE AFFECT IN

6243
04:33:48,400 --> 04:33:56,440
OSTEOARTHRITIS. I'M SURE YOU ARE

6244
04:33:56,440 --> 04:33:58,240
FAMILIAR WITH STANDARDS FOR

6245
04:33:58,240 --> 04:33:59,320
DEFINING EVIDENCE NEEDED FOR

6246
04:33:59,320 --> 04:34:03,080
PRODUCT APPROVAL FOR DRUGS AND

6247
04:34:03,080 --> 04:34:04,640
BIOLOGICS, APPROVAL USUALLY IS

6248
04:34:04,640 --> 04:34:07,080
BASED ON SUBSTANTIAL EVIDENCE OF

6249
04:34:07,080 --> 04:34:08,200
EFFECTIVENESS AND EVIDENCE OF

6250
04:34:08,200 --> 04:34:10,320
SAFETY. AND THAT EVIDENCE SHOULD

6251
04:34:10,320 --> 04:34:13,600
BE OBTAINED FROM ADEQUATE WELL

6252
04:34:13,600 --> 04:34:19,360
CONTROLLED STUDIES. AND FOR

6253
04:34:19,360 --> 04:34:20,760
DEVICES VALID SCIENTIFIC

6254
04:34:20,760 --> 04:34:22,200
EVIDENCE HAS TO BE THERE TO

6255
04:34:22,200 --> 04:34:24,600
DETERMINE WHETHER THERE IS A

6256
04:34:24,600 --> 04:34:26,120
REASONABLE ASSURANCE THE DEVICE

6257
04:34:26,120 --> 04:34:32,000
IS SAFE AND EFFECTIVE. THESE ARE

6258
04:34:32,000 --> 04:34:37,640
REGULATORY CONSIDERATIONS AND

6259
04:34:37,640 --> 04:34:40,880
LYNN GO SO TRANSLATING INTO

6260
04:34:40,880 --> 04:34:43,200
PLAIN LANGUAGE PREVALENT

6261
04:34:43,200 --> 04:34:44,560
CONDITIONS LIKE OSTEOARTHRITIS A

6262
04:34:44,560 --> 04:34:47,760
PRODUCT DEVELOPMENT PROGRAM

6263
04:34:47,760 --> 04:34:49,560
SHOULD CONSIST OF TWO ADEQUATE

6264
04:34:49,560 --> 04:34:51,240
WELL CONTROLLED STUDIES, SHOULD

6265
04:34:51,240 --> 04:34:54,560
BE RANDOMIZED BLINDED AND I HAVE

6266
04:34:54,560 --> 04:34:55,800
A CLINICAL CONTROL GROUP. FOR

6267
04:34:55,800 --> 04:34:59,000
THOSE WHO CONDUCTED TRIALS IN

6268
04:34:59,000 --> 04:35:02,200
OSTEOARTHRITIS POPULATIONS, OR

6269
04:35:02,200 --> 04:35:06,920
FOR FOLKS IN THE FIELD FOR A

6270
04:35:06,920 --> 04:35:09,280
WHILE DR. HOCHBERG AND OTHER

6271
04:35:09,280 --> 04:35:10,760
PARTICIPANTS HAVE DONE TRIALS IN

6272
04:35:10,760 --> 04:35:12,320
OSTEOARTHRITIS, NOT NECESSARILY

6273
04:35:12,320 --> 04:35:14,120
WITH BIOLOGICS BUT OTHER

6274
04:35:14,120 --> 04:35:15,040
COMPOUNDS, YOU PROBABLY KNOW

6275
04:35:15,040 --> 04:35:17,280
THAT ONE OF THE CHALLENGES THAT

6276
04:35:17,280 --> 04:35:19,000
PEOPLE OFTEN SITE SPECIFICALLY

6277
04:35:19,000 --> 04:35:21,280
WITH OA TRIALS IS THAT THERE IS

6278
04:35:21,280 --> 04:35:28,240
A HIGH PLACEBO RESPONSE BELIEVED

6279
04:35:28,240 --> 04:35:30,480
TO BE KNOWN WAXING AND WANING

6280
04:35:30,480 --> 04:35:31,720
SYMPTOMATOLOGY BECAUSE OF

6281
04:35:31,720 --> 04:35:32,520
DISEASE NATURAL HISTORY AND

6282
04:35:32,520 --> 04:35:35,600
PEOPLE HAVE OBSERVED EVEN IF YOU

6283
04:35:35,600 --> 04:35:37,040
ENROLL PATIENTS, WITH MODERATE

6284
04:35:37,040 --> 04:35:40,240
TO HIGH LEVEL OF PAIN, MOST

6285
04:35:40,240 --> 04:35:41,840
PEOPLE BY THE END OF THE STUDY,

6286
04:35:41,840 --> 04:35:43,840
THE PAIN WILL EVENTUALLY SUBSIDE

6287
04:35:43,840 --> 04:35:46,880
TO SOME MODEST DEGREES AND THAT

6288
04:35:46,880 --> 04:35:48,680
COULD HAPPEN REGARDLESS OF THE

6289
04:35:48,680 --> 04:35:52,560
INTERVENTION SO SPECIFICALLY FOR

6290
04:35:52,560 --> 04:35:53,480
OSTEOARTHRITIS TRIALS WE

6291
04:35:53,480 --> 04:35:57,160
RECOMMEND AGAINST HISTORICAL

6292
04:35:57,160 --> 04:35:58,160
CONTROLS, FOR NOVEL PRODUCTS

6293
04:35:58,160 --> 04:36:00,880
RELY ON EVIDENCE THAT COMES FROM

6294
04:36:00,880 --> 04:36:02,800
TRIALS WITH CURRENT CONTROL

6295
04:36:02,800 --> 04:36:08,400
GROUPS. ALONG THE SAME LINES, IN

6296
04:36:08,400 --> 04:36:10,400
ANY CLINICAL TRIAL WITH

6297
04:36:10,400 --> 04:36:13,120
OSTEOARTHRITIS POPULATION,

6298
04:36:13,120 --> 04:36:15,440
POPULATION OF THE DISEASE YOU

6299
04:36:15,440 --> 04:36:17,320
CHOOSE IT SHOULD BE SOME -- AT

6300
04:36:17,320 --> 04:36:19,560
LEAST TO THE DEGREE POSSIBLE

6301
04:36:19,560 --> 04:36:21,280
WELL MATCHED WILL ANTICIPATE

6302
04:36:21,280 --> 04:36:22,360
PRODUCT EFFECT AND THAT IS WHY

6303
04:36:22,360 --> 04:36:23,680
IT IS IMPORTANT TO UNDERSTAND

6304
04:36:23,680 --> 04:36:26,640
WHAT THE PRODUCT ACTUALLY DOES

6305
04:36:26,640 --> 04:36:28,440
BEFORE YOU ADMINISTER TO

6306
04:36:28,440 --> 04:36:37,960
PATIENTS. BEFORE THIS ROUND

6307
04:36:37,960 --> 04:36:39,840
TABLE TED TOLD ME THERE WAS SOME

6308
04:36:39,840 --> 04:36:43,000
INTEREST IN THE TOPIC WE CALL

6309
04:36:43,000 --> 04:36:45,840
TISSUE AND THE MEANING OF

6310
04:36:45,840 --> 04:36:51,120
MINIMAL MANIPULATION AND

6311
04:36:51,120 --> 04:36:53,920
AUTOLOGOUS USE BUTLY DO THAT

6312
04:36:53,920 --> 04:36:55,040
PART MAKING DINTS BETWEEN WHAT

6313
04:36:55,040 --> 04:36:59,320
WE CALL REGULATORY PATHWAYS 351

6314
04:36:59,320 --> 04:37:01,520
PATHWAY, AND 361 PATHWAY. NOW

6315
04:37:01,520 --> 04:37:03,800
REMEMBER I TOLD YOU EARLIER THAT

6316
04:37:03,800 --> 04:37:07,160
THE TWO LAWS WHICH GOVERN DRUG

6317
04:37:07,160 --> 04:37:10,040
BIOLOGICAL PRODUCT DEVELOPMENT

6318
04:37:10,040 --> 04:37:11,680
BY FOOD DRUG ACT AND PUBLIC

6319
04:37:11,680 --> 04:37:13,880
HEALTH SERVICE ACT. UNDER THE

6320
04:37:13,880 --> 04:37:15,440
FOOD DRUG AND (INAUDIBLE) ACT,

6321
04:37:15,440 --> 04:37:19,840
THE RESPECTIVE REGULATIONS

6322
04:37:19,840 --> 04:37:21,120
WHETHER OUTLINED HERE ON THE

6323
04:37:21,120 --> 04:37:22,880
SLIDE ANY USE IN THE UNITED

6324
04:37:22,880 --> 04:37:28,920
STATES OF THE DRUG NOT -- IT IS

6325
04:37:28,920 --> 04:37:31,320
MARKETING APPLICATION TO FDA

6326
04:37:31,320 --> 04:37:34,640
THERE IS A DEFINITION WHAT DRUG

6327
04:37:34,640 --> 04:37:35,720
MEANS FOR DRUG (INAUDIBLE) ACT

6328
04:37:35,720 --> 04:37:38,760
YOU CAN SEE HERE. NOTE THE

6329
04:37:38,760 --> 04:37:40,480
LITTLE FOOTNOTE ON THE SLIDE ALL

6330
04:37:40,480 --> 04:37:42,600
THIS IS APPLICABLE TO BIOLOGICAL

6331
04:37:42,600 --> 04:37:44,000
PRODUCTS TO WELL KNOWN TO ALL OF

6332
04:37:44,000 --> 04:37:46,000
US THERAPEUTIC BIOLOGICAL

6333
04:37:46,000 --> 04:37:49,160
PRODUCTS SUCH AS ANTIBODIES,

6334
04:37:49,160 --> 04:37:51,600
RECEPTOR FUSION PROTEIN,

6335
04:37:51,600 --> 04:37:52,480
ANTI-CYTOKINE TREATMENT MORE

6336
04:37:52,480 --> 04:37:55,440
NOVEL BY SPECIFIC ANTIBODIES. AS

6337
04:37:55,440 --> 04:37:57,720
WELL AS CELL AND GENE THERAPIES

6338
04:37:57,720 --> 04:38:00,480
AND TISSUE GENE PRODUCTS.  IN

6339
04:38:00,480 --> 04:38:03,240
ESSENCE DRUGS REGULATED UNDER

6340
04:38:03,240 --> 04:38:05,120
FOOD DRUG AND BIOLOGICS

6341
04:38:05,120 --> 04:38:07,760
REGULATED UNDER SECTION 3651 OF

6342
04:38:07,760 --> 04:38:09,920
THE PUBLIC HEALTH SERVICE ACT.

6343
04:38:09,920 --> 04:38:12,160
REGULATED IN THE SAME WAY. SO

6344
04:38:12,160 --> 04:38:14,240
ALL THE CONCEPTS AND

6345
04:38:14,240 --> 04:38:15,520
CONSIDERATIONS THAT I HAVE SHOWN

6346
04:38:15,520 --> 04:38:17,600
YOU ON THE PREVIOUS SLIDE RELATE

6347
04:38:17,600 --> 04:38:21,840
TO THE REGULATION OF BIOLOGICS

6348
04:38:21,840 --> 04:38:26,640
UNDER THE 351 PATHWAY SHOWN HERE

6349
04:38:26,640 --> 04:38:31,240
IN RED ON THE SLIDE. SO LET'S

6350
04:38:31,240 --> 04:38:33,600
TALK ABOUT THE 361 PATHWAY WHICH

6351
04:38:33,600 --> 04:38:36,720
IS OUTLINED IN THE PUBLIC HEALTH

6352
04:38:36,720 --> 04:38:39,120
SERVICE ACT BUT BEFORE WE GO

6353
04:38:39,120 --> 04:38:40,520
INTO PATHWAY, LET'S FIRST LOOK

6354
04:38:40,520 --> 04:38:42,520
AT THE SUBSET OF BIOLOGICAL

6355
04:38:42,520 --> 04:38:44,160
PRODUCTS CALLED HUMAN CELLS

6356
04:38:44,160 --> 04:38:47,040
TISSUES AND TISSUE BASED

6357
04:38:47,040 --> 04:38:52,800
PRODUCTS ALSO KNOWN AS HCTPSS.

6358
04:38:52,800 --> 04:38:54,040
SURE YOU HAVE HEARD THIS TERM.

6359
04:38:54,040 --> 04:38:55,520
THE REASON THESE PRODUCTS WERE

6360
04:38:55,520 --> 04:38:58,280
DEFINED LIKE THIS AND WHY THE

6361
04:38:58,280 --> 04:39:00,720
TISSUE WAS EVEN CREATED WAS TO

6362
04:39:00,720 --> 04:39:04,240
PERMIT THE USE OF DONOR DERIVED

6363
04:39:04,240 --> 04:39:07,320
OR AUTOLOGOUS HUMAN TISSUES AND

6364
04:39:07,320 --> 04:39:08,880
CELLS PRIMARILY FOR CORRECTION

6365
04:39:08,880 --> 04:39:12,960
OF ANATOMICAL DEFECTS OR CELL

6366
04:39:12,960 --> 04:39:15,120
SUPPLEMENTATION IN LOWER RISK

6367
04:39:15,120 --> 04:39:17,680
SITUATIONS WHEN THERE IS A GOOD

6368
04:39:17,680 --> 04:39:18,760
ASSURANCE THERE WOULD BE NO

6369
04:39:18,760 --> 04:39:22,040
TRANSMISSION OF INFECTIOUS

6370
04:39:22,040 --> 04:39:25,360
DISEASE DO DONOR TO RECIPIENT.

6371
04:39:25,360 --> 04:39:31,880
THE DONOR COULD BE A LIVE DONOR

6372
04:39:31,880 --> 04:39:37,280
OR A -- A CLAYS IS EXAMPLE IS A

6373
04:39:37,280 --> 04:39:40,800
CORNEAL IMPLANT. JUST REPLACE

6374
04:39:40,800 --> 04:39:44,120
PROVIDED THE ADEQUATE QUALITY

6375
04:39:44,120 --> 04:39:46,320
AND PURITY, MANUFACTURER

6376
04:39:46,320 --> 04:39:47,360
RESPONSIBLE FOR MAKING THE

6377
04:39:47,360 --> 04:39:49,560
PRODUCT, THERE IS ABSENCE OF

6378
04:39:49,560 --> 04:39:50,760
TRANSMISSIBLE INFECTION WHICH

6379
04:39:50,760 --> 04:39:52,360
CAN BE ASSURED THROUGH

6380
04:39:52,360 --> 04:39:56,920
APPROPRIATE DONOR ELIGIBILITY

6381
04:39:56,920 --> 04:39:58,600
CRITERIA. YOU CAN DO THE

6382
04:39:58,600 --> 04:40:02,200
IMPLEMENTATION SURGICALLY. HCCP

6383
04:40:02,200 --> 04:40:04,240
REGULATION COLLECTIVELY KNOWN AS

6384
04:40:04,240 --> 04:40:05,960
TISSUE DEFINE TWO THINGS. THEY

6385
04:40:05,960 --> 04:40:08,280
DEFINE A NUMBER OF THINGS BUT

6386
04:40:08,280 --> 04:40:09,960
DEFINE TWO IMPORTANT THINGS,

6387
04:40:09,960 --> 04:40:11,840
IMPORTANT FOR OUR CONVERSATION

6388
04:40:11,840 --> 04:40:15,040
TODAY. HCTP PRODUCTS WHICH

6389
04:40:15,040 --> 04:40:17,280
TISSUE MAYBE APPLICABLE, A GROUP

6390
04:40:17,280 --> 04:40:19,560
OF PRODUCTS WHICH YOU SEE HERE

6391
04:40:19,560 --> 04:40:23,120
ON THE SLIDE, THEY ALSO DEFINE

6392
04:40:23,120 --> 04:40:24,480
CRITERIA WHEN HE IS PRODUCTS CAN

6393
04:40:24,480 --> 04:40:28,440
BE REGULATED UNDER TISSUE AND

6394
04:40:28,440 --> 04:40:32,080
NOT UNDER SECTION 351 OF PUBLIC

6395
04:40:32,080 --> 04:40:33,400
HEALTH SERVICE ACT. BY AND LARGE

6396
04:40:33,400 --> 04:40:34,960
MOST PRODUCTS WHEN THEY ARE

6397
04:40:34,960 --> 04:40:38,280
INTENDED FOR TREATMENT OF

6398
04:40:38,280 --> 04:40:40,560
DISEASES, THEY REGULATE UNDER

6399
04:40:40,560 --> 04:40:43,880
351 PATHWAY. LET'S TALK ABOUT

6400
04:40:43,880 --> 04:40:46,600
DEFINITION FIRST. HCTPs ARE

6401
04:40:46,600 --> 04:40:48,720
HUMAN CELLS AND TISSUE PRODUCTS

6402
04:40:48,720 --> 04:40:51,360
INTENDED FOR IMPLANTATION

6403
04:40:51,360 --> 04:40:52,160
TRANSPLANTATION AND FUSION OR

6404
04:40:52,160 --> 04:40:56,760
TRANSFER TO HUMAN RECIPIENTSS.

6405
04:40:56,760 --> 04:40:58,760
THEY COVER A RANGE OF PRODUCTS

6406
04:40:58,760 --> 04:41:03,400
YOU SEE HERE IN T SECOND BULLET.

6407
04:41:03,400 --> 04:41:06,440
PLEASE KNOW MOST PRODUCTS ARE

6408
04:41:06,440 --> 04:41:07,760
REGULATED AS DRUGS OR BIOLOGICAL

6409
04:41:07,760 --> 04:41:09,200
PRODUCTS PARTICULARLY WHEN THEY

6410
04:41:09,200 --> 04:41:10,640
ARE INTENDED TO TREAT MEDICAL

6411
04:41:10,640 --> 04:41:13,040
CONDITIONS. OSTEOARTHRITIS WAS

6412
04:41:13,040 --> 04:41:17,240
NO EXCEPTION HERE. SOME WOULD BE

6413
04:41:17,240 --> 04:41:20,520
REGULATED UNDER TISSUE IF THEY

6414
04:41:20,520 --> 04:41:21,880
MEET SPECIFIC CRITERIA, I WILL

6415
04:41:21,880 --> 04:41:29,440
SHOW YOU IN A MINUTE. THE HCTP

6416
04:41:29,440 --> 04:41:31,800
REGULATION DEFINE PRODUCTS NOT

6417
04:41:31,800 --> 04:41:34,360
HCTPs, THESE INCLUDE BLOOD

6418
04:41:34,360 --> 04:41:36,240
PRODUCTS PLATELET RICH PLASMA

6419
04:41:36,240 --> 04:41:38,360
AND SERUM. BECAUSE PRODUCTS ARE

6420
04:41:38,360 --> 04:41:42,440
NOT HCTPs, THEY ARE NOT

6421
04:41:42,440 --> 04:41:43,560
SUBJECTS TO THE FRAMEWORK OF THE

6422
04:41:43,560 --> 04:41:47,080
TISSUE OR THE 361 PATHWAYS. A

6423
04:41:47,080 --> 04:41:48,960
PATHWAY, THEY CANNOT BE MADE

6424
04:41:48,960 --> 04:41:53,280
AVAILABLE UNDER THIS FRAMEWORK.

6425
04:41:53,280 --> 04:41:59,200
THE REGS DR. CHU SHOWED US

6426
04:41:59,200 --> 04:42:01,440
BEGINNING 640 APPLY TO BLOOD

6427
04:42:01,440 --> 04:42:02,280
PRODUCTS INTENDED FOR

6428
04:42:02,280 --> 04:42:06,520
TRANSFUSION.  NOTHING TO DO WITH

6429
04:42:06,520 --> 04:42:10,280
TREATING MEDICAL CONDITIONS.  

6430
04:42:10,280 --> 04:42:11,520
THE REASON I ASK FOR A LITTLE

6431
04:42:11,520 --> 04:42:14,280
MORE TIME, I WANT TO MAYBE

6432
04:42:14,280 --> 04:42:17,840
DISPEL MYTHS OR EXPLAIN

6433
04:42:17,840 --> 04:42:19,080
MISCONCEPTIONS. THE FIRST

6434
04:42:19,080 --> 04:42:20,520
INCEPTION OBVIOUSLY YOU MIGHT

6435
04:42:20,520 --> 04:42:25,600
HEAR OPRP WOULD BE LEGALLY

6436
04:42:25,600 --> 04:42:28,880
MARKETED PRODUCT OR LEGALLY

6437
04:42:28,880 --> 04:42:31,280
MARKETED AS AN HCTP, HUMAN

6438
04:42:31,280 --> 04:42:33,360
TISSUE PRODUCT. THAT IS NOT

6439
04:42:33,360 --> 04:42:36,360
CORRECT. BECAUSE PRP IS NOT

6440
04:42:36,360 --> 04:42:37,840
HCTP, IT DOESN'T FALL UNDER

6441
04:42:37,840 --> 04:42:41,800
TISSUE. SO I WILL GIVE A LITTLE

6442
04:42:41,800 --> 04:42:43,880
HISTORY HERE. HCTP REGULATIONS

6443
04:42:43,880 --> 04:42:48,480
WERE ISSUED THROUGH NOTICE OF

6444
04:42:48,480 --> 04:42:50,960
COMMON RULE MAKING IN EARLY

6445
04:42:50,960 --> 04:42:54,040
2000s. ISSUED IN THREE PARTS

6446
04:42:54,040 --> 04:42:56,400
AND BECAME COLLECTIVELY KNOWN AS

6447
04:42:56,400 --> 04:42:59,280
THE TISSUE, THEY BECAME FULLY

6448
04:42:59,280 --> 04:43:01,360
EFFECTIVE IN MAY OF 2005. SO

6449
04:43:01,360 --> 04:43:04,680
HERE IS ANOTHER EXAMPLE OF THE

6450
04:43:04,680 --> 04:43:07,720
MISCONCEPTION WE OFTEN HEAR FDA

6451
04:43:07,720 --> 04:43:09,200
JUST STARTED REGULATING THIS

6452
04:43:09,200 --> 04:43:11,880
PRODUCT OR FDA DIDN'T REGULATE

6453
04:43:11,880 --> 04:43:13,760
THE PRODUCT BEFORE THEY

6454
04:43:13,760 --> 04:43:16,920
PUBLISHED THEIR DRAFT GUIDANCE

6455
04:43:16,920 --> 04:43:19,800
IN 2017. THESE STATEMENTS ARE

6456
04:43:19,800 --> 04:43:22,320
NOT ACCURATE. FDA HAS BEEN

6457
04:43:22,320 --> 04:43:23,360
REGULATING THESE PRODUCTS UNDER

6458
04:43:23,360 --> 04:43:26,040
THE SAME FRAMEWORK FOR MORE THAN

6459
04:43:26,040 --> 04:43:27,840
17 YEARS, THE GUIDANCE AND

6460
04:43:27,840 --> 04:43:30,280
MINIMAL MANIPULATION AND

6461
04:43:30,280 --> 04:43:30,760
HOMOLOGY GUS USE INCLUDE

6462
04:43:30,760 --> 04:43:32,560
MISDEMEANOR THE LIST OF READING

6463
04:43:32,560 --> 04:43:36,000
MATERIALS FOR THE ROUND TABLE,

6464
04:43:36,000 --> 04:43:39,000
AND OTHER RELATED GUIDANCE ABOUT

6465
04:43:39,000 --> 04:43:41,280
TISSUE WERE WRITTEN TO PROVIDE

6466
04:43:41,280 --> 04:43:43,840
CLARITY AROUND THE REGULATIONS

6467
04:43:43,840 --> 04:43:46,440
THEY DID NOT REALLY SERVE TO

6468
04:43:46,440 --> 04:43:47,960
BRING ANY PRODUCT UNDER THE FDA

6469
04:43:47,960 --> 04:43:58,400
AUTHORITY. HCTPs CAN BE

6470
04:44:00,240 --> 04:44:01,640
REGULATED AS I TOLD YOU AS DRUGS

6471
04:44:01,640 --> 04:44:03,760
OR BIOLOGICAL PRODUCTS. AND THAT

6472
04:44:03,760 --> 04:44:05,440
IS WHEN THEY ARE INTENDED FOR

6473
04:44:05,440 --> 04:44:08,760
MEDICAL TREATMENT OF DISEASE

6474
04:44:08,760 --> 04:44:11,080
CHRONIC MEDICAL CONDITIONS,

6475
04:44:11,080 --> 04:44:13,080
NEUROLOGICAL CONDITIONS

6476
04:44:13,080 --> 04:44:14,840
MUSCULOSKELETAL DISORDERS

6477
04:44:14,840 --> 04:44:16,160
INCLUDING OSTEOARTHRITIS. FDA

6478
04:44:16,160 --> 04:44:18,320
PRE-MARKET REVIEW APPROVAL WOULD

6479
04:44:18,320 --> 04:44:21,520
BE REQUIRED FOR THESE PRODUCTS

6480
04:44:21,520 --> 04:44:23,080
WHICH MEANS THEY CANNOT BE

6481
04:44:23,080 --> 04:44:24,880
MARKETED WITHOUT APPROVED

6482
04:44:24,880 --> 04:44:26,600
BIOLOGIC LICENSE APPLICATION AND

6483
04:44:26,600 --> 04:44:31,120
THEY CAN BE MADE AVAILABLE

6484
04:44:31,120 --> 04:44:32,360
ASVATIONAL PRODUCTS UNDER ACTIVE

6485
04:44:32,360 --> 04:44:35,440
IND OR IDE.  THE SECOND SCENARIO

6486
04:44:35,440 --> 04:44:40,480
YOU SEE HERE ON THE SLIDE, WHEN

6487
04:44:40,480 --> 04:44:43,520
HCTP MEETS SPECIFIC CRITERIA

6488
04:44:43,520 --> 04:44:45,400
UNDER SECTION 361 PUBLIC HEALTH

6489
04:44:45,400 --> 04:44:49,720
SERVICE ACT IN THAT CASE HCTP

6490
04:44:49,720 --> 04:44:50,760
PRODUCT WOULDN'T REQUIRE FDA

6491
04:44:50,760 --> 04:44:52,520
PRE-MARKET REVIEW AND APPROVAL

6492
04:44:52,520 --> 04:44:57,400
AS EXPLAINED IN THE CASE OF

6493
04:44:57,400 --> 04:44:59,000
CORNEAL IMPLANT WHICH IS

6494
04:44:59,000 --> 04:45:00,200
PRODUCTS LIKE THIS CAN BE

6495
04:45:00,200 --> 04:45:01,880
MARKETED AND MADE AVAILABLE SO

6496
04:45:01,880 --> 04:45:04,840
LONG AS THEY MEET THE CRITERIA.

6497
04:45:04,840 --> 04:45:07,000
PLEASE NOTE HERE MANUFACTURERS

6498
04:45:07,000 --> 04:45:10,640
OF THESE PRODUCTS STILL HAVE TO

6499
04:45:10,640 --> 04:45:12,880
REGISTER WITH THE FDA AS

6500
04:45:12,880 --> 04:45:16,920
FACILITY THAT MAKES HCTPs AND

6501
04:45:16,920 --> 04:45:19,040
SUBJECT TO SAFETY REPORTING

6502
04:45:19,040 --> 04:45:21,480
MANUAL REPORTING WHICH MEANS IF

6503
04:45:21,480 --> 04:45:24,040
SOMETHING HAPPENS WITH HAIR

6504
04:45:24,040 --> 04:45:25,920
PRODUCT WHEN MARKETED AND IF

6505
04:45:25,920 --> 04:45:27,920
RELATED TO SAFETY THEY HAVE TO

6506
04:45:27,920 --> 04:45:30,760
REPORT THIS TO FDA AND WE WILL

6507
04:45:30,760 --> 04:45:32,080
LOOK AFTER SAFETY OF THESE

6508
04:45:32,080 --> 04:45:42,640
PRODUCTS TOO. HERE ARE THE FOUR

6509
04:45:45,080 --> 04:45:49,080
CRITERIA. DEFINED IN TISSUE. 

6510
04:45:49,080 --> 04:45:52,120
PLEASE NOTE ALL OF THESE

6511
04:45:52,120 --> 04:45:53,840
CRITERIA MUST BE MET IN ORDER

6512
04:45:53,840 --> 04:45:58,040
FOR HCTP TO BE REGULATED SOLELY

6513
04:45:58,040 --> 04:46:00,680
UNDER SECTION 361. HERE THEY

6514
04:46:00,680 --> 04:46:03,520
ARE. THE PRODUCT HAS TO BE

6515
04:46:03,520 --> 04:46:05,400
MINIMALLY MANIPULATED, INTENDED

6516
04:46:05,400 --> 04:46:10,960
FOR HOMOLOGOUS USE, NOT COMBINED

6517
04:46:10,960 --> 04:46:12,640
ANOTHER ARTICLE OR SUBSTANCE AND

6518
04:46:12,640 --> 04:46:15,480
A PRODUCT HCTP REGULATED UNDER

6519
04:46:15,480 --> 04:46:18,320
361 CAN LOOK AT THE SYSTEMIC

6520
04:46:18,320 --> 04:46:19,880
EFFECT OR P DEPENDENT ON THE

6521
04:46:19,880 --> 04:46:21,800
METABOLIC ACTIVITY OF THE LIVING

6522
04:46:21,800 --> 04:46:27,280
CELLS FOR PRIMARY FUNCTION

6523
04:46:27,280 --> 04:46:29,280
AUTOLOGOUS PRODUCT INTENDED IN

6524
04:46:29,280 --> 04:46:31,360
THE USE OF FIRST OF SECOND

6525
04:46:31,360 --> 04:46:33,360
DEGREE RELATIVE OR FOR

6526
04:46:33,360 --> 04:46:34,720
REPRODUCTIVE USE. HERE IS

6527
04:46:34,720 --> 04:46:36,160
ANOTHER MISCONCEPTION WHICH I

6528
04:46:36,160 --> 04:46:37,880
NOT ONLY SAW IN THE RESPONSES TO

6529
04:46:37,880 --> 04:46:40,560
QUESTIONS, FOR THE ROUND TABLE

6530
04:46:40,560 --> 04:46:42,840
BUT ALSO HEARD DURING THE

6531
04:46:42,840 --> 04:46:45,040
DISCUSSION. WE HAVE HEAR FOLKS

6532
04:46:45,040 --> 04:46:48,760
SAY BECAUSE THIS PRODUCT IS AN

6533
04:46:48,760 --> 04:46:51,280
AUTOLOGOUS PRODUCT IT IS

6534
04:46:51,280 --> 04:46:54,480
AUTOMATICALLY HCTP AND

6535
04:46:54,480 --> 04:46:55,840
AUTOMATICALLY FDA.  THIS IS NOT

6536
04:46:55,840 --> 04:46:58,320
TRUE BECAUSE WE HAVE MEN PLENTY

6537
04:46:58,320 --> 04:47:01,520
OF AUTOLOGOUS PRODUCTS REGULATED

6538
04:47:01,520 --> 04:47:04,760
UNDER 351. HCTP MUST IMMEDIATE

6539
04:47:04,760 --> 04:47:06,560
ALL FOUR CRITERIA TO BE

6540
04:47:06,560 --> 04:47:08,360
REGULATED SOLELY UNDER SECTION

6541
04:47:08,360 --> 04:47:17,840
361. SO THIS GUIDANCE SURE YOU

6542
04:47:17,840 --> 04:47:19,040
READ IT IF PREPARING FOR THE

6543
04:47:19,040 --> 04:47:23,360
ROUND TABLE, THIS GUIDANCE

6544
04:47:23,360 --> 04:47:27,880
DISCUSSES ROLE APPROACH TO

6545
04:47:27,880 --> 04:47:28,520
SELF-DETERMINATION OF WHAT

6546
04:47:28,520 --> 04:47:30,200
PRODUCT YOU ARE WORKING WITH AND

6547
04:47:30,200 --> 04:47:33,840
WHETHER THE PRODUCT WOULD FALL

6548
04:47:33,840 --> 04:47:35,920
UNDER THE TISSUE REGULATIONS, IT

6549
04:47:35,920 --> 04:47:37,960
PROVIDE AN ALGORITHM AND TALKS

6550
04:47:37,960 --> 04:47:39,400
ABOUT THE FIRST TWO CRITERIA

6551
04:47:39,400 --> 04:47:50,000
WHICH I WILL ALSO DISCUSS TODAY 

6552
04:47:52,440 --> 04:47:53,720
NOT TOO EASY TO MOVE THE SLIDES,

6553
04:47:53,720 --> 04:47:59,480
NOT SURE WHY. SO THE FIRST

6554
04:47:59,480 --> 04:48:02,760
CRITERIA SAYS HCTP MUST BE

6555
04:48:02,760 --> 04:48:05,320
MINIMALLY MANIPULATED. THE

6556
04:48:05,320 --> 04:48:07,000
REGULATIONS LAY OUT TWO SEPARATE

6557
04:48:07,000 --> 04:48:09,760
DEFINITIONS OF MINIMAL

6558
04:48:09,760 --> 04:48:12,880
MANIPULATION. ONE IS STRUCTURAL

6559
04:48:12,880 --> 04:48:15,000
TISSUES AND THE OTHER IS

6560
04:48:15,000 --> 04:48:16,480
CELLULAR AND NON-STRUCTURAL

6561
04:48:16,480 --> 04:48:19,920
TISSUES. WHEN EVALUATING THE

6562
04:48:19,920 --> 04:48:20,560
MINIMUM NARRATION CRITERIA, IT

6563
04:48:20,560 --> 04:48:21,920
IS IMPORTANT TO REMEMBER THAT

6564
04:48:21,920 --> 04:48:28,640
THIS CRITERIA RELATES TO HOW THE

6565
04:48:28,640 --> 04:48:30,080
HCTP FUNCTION IN THE DONOR, IT

6566
04:48:30,080 --> 04:48:32,480
IS ESSENTIAL TO EVALUATE

6567
04:48:32,480 --> 04:48:34,320
PROCESSING STEPS AND BEGIN

6568
04:48:34,320 --> 04:48:36,560
ANALYSIS WITH THE HCTP AS

6569
04:48:36,560 --> 04:48:39,120
EXISTED IN THE DONOR. SO THIS

6570
04:48:39,120 --> 04:48:40,920
MEANS YOU LOOK AT THE PROCESSING

6571
04:48:40,920 --> 04:48:43,880
FROM START TO FINISH AND IN THE

6572
04:48:43,880 --> 04:48:45,640
PROCESSING ORDERS TISSUES

6573
04:48:45,640 --> 04:48:47,560
UTILITY IN THE DONOR, MEANING

6574
04:48:47,560 --> 04:48:50,880
THAT THE TISSUE LOST ABILITY TO

6575
04:48:50,880 --> 04:48:53,080
FUNCTION AS IT DID IN THE DONOR,

6576
04:48:53,080 --> 04:48:54,560
THEN WE WOULD CONSIDER THE

6577
04:48:54,560 --> 04:48:56,200
PROCESSING TO BE MORE THAN

6578
04:48:56,200 --> 04:48:57,680
MINIMAL MANIPULATION. GUIDANCE

6579
04:48:57,680 --> 04:48:59,240
INCLUDES A NUMBER OF EXAMPLES

6580
04:48:59,240 --> 04:49:01,480
BECAUSE YOU HAVE TO APPLY THESE

6581
04:49:01,480 --> 04:49:05,360
CRITERIA BASED ON NOT ONLY

6582
04:49:05,360 --> 04:49:10,000
PROCESS OF MANIPULATION BUT ALSO

6583
04:49:10,000 --> 04:49:13,560
APPLICATION TO DIFFERENT TISSUES

6584
04:49:13,560 --> 04:49:15,600
THAT MAY VARY, THE APPLICATION

6585
04:49:15,600 --> 04:49:17,840
MAY VARY FOR DIFFERENT TISSUES.

6586
04:49:17,840 --> 04:49:28,400
THE SECOND CRITERIA HERE IS THE

6587
04:49:31,520 --> 04:49:33,000
HOMOLOGOUS USE. HOMOLOGOUS USE

6588
04:49:33,000 --> 04:49:36,040
IS DEFINED IN THE REGS AS REPAIR

6589
04:49:36,040 --> 04:49:38,280
RECONSTRUCTION REPLACEMENT OR

6590
04:49:38,280 --> 04:49:39,960
SUPPLEMENTATION OF RECIPIENT

6591
04:49:39,960 --> 04:49:44,720
CELLS OR TISSUES WITH HCTP THAT

6592
04:49:44,720 --> 04:49:45,920
PERFORMS THE SAME FUNCTION OR

6593
04:49:45,920 --> 04:49:48,600
FUNCTIONS IN THE RECIPIENT AS IN

6594
04:49:48,600 --> 04:49:51,960
THE DONOR. KEY POINT HERE TO

6595
04:49:51,960 --> 04:49:54,320
KEEP IN MIND IS THIS CRITERION

6596
04:49:54,320 --> 04:49:56,120
RELATES TO THE INTENDED USE OF

6597
04:49:56,120 --> 04:50:01,360
THE HCTP IN THE RECIPIENT IF YOU

6598
04:50:01,360 --> 04:50:03,760
INTEND TO USE HCTP FOR THE

6599
04:50:03,760 --> 04:50:06,240
INTENDED FUNCTION IN RECIPIENT

6600
04:50:06,240 --> 04:50:08,640
IN ORDER TO MEET HOMOLOGOUS USE

6601
04:50:08,640 --> 04:50:10,440
CRITERION ACTION HCTP PERFORMED

6602
04:50:10,440 --> 04:50:11,640
THE SAME BASIC FUNCTION IN THE

6603
04:50:11,640 --> 04:50:15,680
DONOR.  IT IS IMPORTANT TO

6604
04:50:15,680 --> 04:50:17,120
REMEMBER CLINICAL EFFECT OF

6605
04:50:17,120 --> 04:50:19,280
TISSUE THAT ARE NOT ALSO BASIC

6606
04:50:19,280 --> 04:50:21,520
FUNCTION OF THE TISSUE IN THE

6607
04:50:21,520 --> 04:50:23,760
DONOR, ARE NOT CONSIDERED BASIC

6608
04:50:23,760 --> 04:50:27,280
FUNCTIONS. THIS MEANS BECAUSE

6609
04:50:27,280 --> 04:50:28,760
SOMEONE DEMON INVESTIGATORY HUE

6610
04:50:28,760 --> 04:50:30,440
CAN PERFORM FUNCTION IN THE

6611
04:50:30,440 --> 04:50:32,720
RECIPIENT, THIS DOESN'T MEAN THE

6612
04:50:32,720 --> 04:50:35,240
FUNCTION IS NECESSARILY BASIC

6613
04:50:35,240 --> 04:50:37,280
FUNCTION. SO NEEDLESS TO SAY IF

6614
04:50:37,280 --> 04:50:39,480
YOU HAVE A PRODUCT THAT IS

6615
04:50:39,480 --> 04:50:42,360
INTENDED FOR TREATMENT OF

6616
04:50:42,360 --> 04:50:45,240
MEDICAL CONDITIONS LET ALONE A

6617
04:50:45,240 --> 04:50:47,200
MYRIAD OF DIFFERENT CONDITIONS,

6618
04:50:47,200 --> 04:50:49,520
THE SAME PRODUCT HCTP IS NOT

6619
04:50:49,520 --> 04:50:58,400
INTENDED FOR HOMOLOGOUS USE. I

6620
04:50:58,400 --> 04:50:59,640
PROMISED TO SHOW YOU GUIDANCE

6621
04:50:59,640 --> 04:51:00,760
AND I THINK THE FOUR GUIDANCES

6622
04:51:00,760 --> 04:51:04,120
THAT ARE HERE IN THE BULLETS ARE

6623
04:51:04,120 --> 04:51:07,440
MUST READ FOR FOLKS WHO ARE

6624
04:51:07,440 --> 04:51:09,320
DEVELOPING PRODUCTS, THE LINK ON

6625
04:51:09,320 --> 04:51:13,480
THE SLIDE WILL TAKE YOU TO OUR

6626
04:51:13,480 --> 04:51:15,640
WEBSITE WHERE YOU CAN FIND OTHER

6627
04:51:15,640 --> 04:51:18,880
GUIDANCE FOR DIFFERENT DISEASE

6628
04:51:18,880 --> 04:51:22,640
AND CONDITIONS AND OTHER

6629
04:51:22,640 --> 04:51:23,840
PRODUCTS THAT REGULATE NOT

6630
04:51:23,840 --> 04:51:25,520
NECESSARILY CELLULAR PRODUCTS

6631
04:51:25,520 --> 04:51:28,720
ALONE AS WELL AS ADDITIONAL

6632
04:51:28,720 --> 04:51:30,040
GUIDANCE ON THE TISSUE BECAUSE I

6633
04:51:30,040 --> 04:51:31,560
RECOGNIZE WE ARE TALKING ONLY

6634
04:51:31,560 --> 04:51:40,680
ABOUT ONE GUIDANCE TODAY.  BY

6635
04:51:40,680 --> 04:51:45,640
POPULAR DEMAND. SO THIS LOOKS

6636
04:51:45,640 --> 04:51:46,880
LIKE MY LAST SLIDE. THANK YOU

6637
04:51:46,880 --> 04:51:48,840
FOR YOUR ATTENTION. HERE IS MY

6638
04:51:48,840 --> 04:51:50,040
EMAIL AND THE CONTACT

6639
04:51:50,040 --> 04:51:50,720
INFORMATION FOR THE OFFICE IF

6640
04:51:50,720 --> 04:51:56,280
YOU HAVE ANY QUESTIONS DO NOT

6641
04:51:56,280 --> 04:51:59,120
HESITATE TO SEND YOUR QUESTIONS

6642
04:51:59,120 --> 04:52:01,480
AND ASK THEM AND WE ARE

6643
04:52:01,480 --> 04:52:02,720
DEVELOPING MORE ONLINE RESOURCES

6644
04:52:02,720 --> 04:52:07,920
FOR STAKEHOLDERS PUBLISHED IN

6645
04:52:07,920 --> 04:52:10,560
THE UPCOMING YEAR. THANKS AND

6646
04:52:10,560 --> 04:52:20,640
GLAD TO JOIN DISCUSSION. 

6647
04:52:20,640 --> 04:52:24,360
>>THANK YOU SO MUCH.
PRETTY

6648
04:52:24,360 --> 04:52:27,600
CLEAR IN OUR DISCUSSION WE ARE

6649
04:52:27,600 --> 04:52:29,840
NEEDING BETTER CHARACTERIZATION,

6650
04:52:29,840 --> 04:52:31,720
WE ARE NEEDING TO KNOW BETTER

6651
04:52:31,720 --> 04:52:35,240
WHAT WE ARE GIVING PATIENTS SO

6652
04:52:35,240 --> 04:52:39,840
ALL THOSE AMOUNT TO DOING MORE

6653
04:52:39,840 --> 04:52:42,320
QUOTE UNQUOTE MANIPULATION AND

6654
04:52:42,320 --> 04:52:46,200
YOU GET ALL THE WAY UP TO WHAT

6655
04:52:46,200 --> 04:52:49,280
DR. GUILAK SHOWED WHERE IT IS A

6656
04:52:49,280 --> 04:52:55,080
VERY INTRICATE CELLULAR ENGIN 

6657
04:52:55,080 --> 04:52:56,560
ENGINEERING SO I WOULD SAY IT IS

6658
04:52:56,560 --> 04:53:01,600
PROBABLY IMPORTANT FOR US TO AS

6659
04:53:01,600 --> 04:53:06,320
SCIENTISTS TO WALK AWAY FROM

6660
04:53:06,320 --> 04:53:09,920
THIS 361 AS A -- I THINK THAT

6661
04:53:09,920 --> 04:53:14,320
THAT HAS BEEN A I ALMOST WANT TO

6662
04:53:14,320 --> 04:53:16,560
SAY LOOP HOLE WHERE SO MANY

6663
04:53:16,560 --> 04:53:17,360
PRODUCTS SO TO SPEAK HAVE GONE

6664
04:53:17,360 --> 04:53:21,080
OUT TO THE COMMUNITY AND FOR US

6665
04:53:21,080 --> 04:53:22,520
TO START THINKING WE NEED TO GO

6666
04:53:22,520 --> 04:53:31,960
BACK TO BASICS AND SAY WHAT

6667
04:53:31,960 --> 04:53:38,320
PATHOLOGY AND PATHOGENETIC POINT

6668
04:53:38,320 --> 04:53:40,320
ARE WE TRYING TO CONVENE AT AND

6669
04:53:40,320 --> 04:53:42,840
HOW IS THIS A BIOLOGIC -- WE ARE

6670
04:53:42,840 --> 04:53:45,040
TALKING BIOLOGICS BUT WHERE IN

6671
04:53:45,040 --> 04:53:49,640
THAT PATHWAY IS THIS BIOLOGIC

6672
04:53:49,640 --> 04:53:52,320
INTENDED OR WE THINK IT ACTS

6673
04:53:52,320 --> 04:53:54,080
BASED ON RESEARCH WE HAVE DONE

6674
04:53:54,080 --> 04:53:58,160
IN PRE-CLINICAL MODELS IN VITRO

6675
04:53:58,160 --> 04:54:05,880
AND MOVE INTO CLINICAL

6676
04:54:05,880 --> 04:54:08,240
TRANSLATION. I DO WANT TO GET A

6677
04:54:08,240 --> 04:54:14,200
SPECIFIC CLARIFICATION REGARDING

6678
04:54:14,200 --> 04:54:21,200
PRP. WIDELY USED AND REALLY THE

6679
04:54:21,200 --> 04:54:24,840
PRP AS YOU MENTION, IS COVERED

6680
04:54:24,840 --> 04:54:26,840
UNDER BLOOD. THE WHOLE INTENTION

6681
04:54:26,840 --> 04:54:29,200
WAS FOR TRANSFUSION WITH PRP

6682
04:54:29,200 --> 04:54:31,760
BEING DISCUSSED BECAUSE IT IS AN

6683
04:54:31,760 --> 04:54:34,840
INTERMEDIATE STEP IN THE

6684
04:54:34,840 --> 04:54:36,800
CREATION OF FRESH FROZEN

6685
04:54:36,800 --> 04:54:39,680
PLATELETS. FFP AND PLATELET

6686
04:54:39,680 --> 04:54:49,320
CONCENTRATE. WHY DOES PRP

6687
04:54:49,320 --> 04:54:50,680
FOLLOW? BECAUSE USE IS OUT

6688
04:54:50,680 --> 04:54:55,080
THERE, GREATLY EXCEED ANYTHING

6689
04:54:55,080 --> 04:54:58,040
EVER IMAGINED FOR

6690
04:54:58,040 --> 04:55:02,960
TRANSPLANTATION -- BLOOD

6691
04:55:02,960 --> 04:55:04,440
TRANSFUSION.

6692
04:55:04,440 --> 04:55:11,200
>>WE DO HAVE BOTH ID

6693
04:55:11,200 --> 04:55:12,480
INVESTIGATIONAL DEVICE

6694
04:55:12,480 --> 04:55:13,960
APPLICATIONS ANDVATIONAL MU DRUG

6695
04:55:13,960 --> 04:55:15,960
APPROXIMATE -- INVESTIGATIONAL

6696
04:55:15,960 --> 04:55:19,280
DRUG APPLICATIONS PRP. WHEN IT

6697
04:55:19,280 --> 04:55:22,320
WAS INTENDED FOR TREATMENT FOR

6698
04:55:22,320 --> 04:55:26,960
DISEASE MEDICAL CONDITIONS WE

6699
04:55:26,960 --> 04:55:31,880
LOOK AT THOSE PROGRAMS.

6700
04:55:31,880 --> 04:55:32,840
OSTEOARTHRITIS IT IS ONE THING

6701
04:55:32,840 --> 04:55:36,160
USED FOR WOUND HEALING. SO WE

6702
04:55:36,160 --> 04:55:38,360
HAVE INVESTIGATIONAL DEVICE

6703
04:55:38,360 --> 04:55:44,560
EXEMPTION APPLICATIONS FOR POINT

6704
04:55:44,560 --> 04:55:47,680
OF CARE DEVICE PRP DEVICE COULD

6705
04:55:47,680 --> 04:55:51,320
BE PRODUCED IF IT HAS EFFECTS ON

6706
04:55:51,320 --> 04:55:54,800
WOUND HEALING FOR OTHER DISEASES

6707
04:55:54,800 --> 04:55:56,320
OR CONDITIONS WE SEE THOSE

6708
04:55:56,320 --> 04:56:00,400
DEVELOPMENT PATHWAYS AND

6709
04:56:00,400 --> 04:56:03,320
EVALUATIONS AND INVESTIGATION

6710
04:56:03,320 --> 04:56:09,200
DONE WITH PRP.  CURRENTLY OUR

6711
04:56:09,200 --> 04:56:12,080
USE IN OSTEOARTHRITIS FALLS

6712
04:56:12,080 --> 04:56:19,520
UNDER A -- PHYSICIAN DISCRETION?

6713
04:56:19,520 --> 04:56:23,200
HOW WOULD YOU FROM FDA

6714
04:56:23,200 --> 04:56:24,320
STANDPOINT CHARACTERIZE THE

6715
04:56:24,320 --> 04:56:28,000
BASIS FOR USE IN OSTEOARTHRITIS 

6716
04:56:28,000 --> 04:56:31,440
>>I DON'T USE IT IN

6717
04:56:31,440 --> 04:56:33,640
OSTEOARTHRITIS SO -- IT WOULD BE

6718
04:56:33,640 --> 04:56:34,800
INTERESTING TO UNDERSTAND WHAT

6719
04:56:34,800 --> 04:56:36,920
YOU ARE TELLING TO YOUR PATIENTS

6720
04:56:36,920 --> 04:56:40,880
WHEN YOU ARE OFFERING THEM THIS

6721
04:56:40,880 --> 04:56:44,040
TREATMENT WHETHER -- HOW DO YOU

6722
04:56:44,040 --> 04:56:46,960
EVEN SAY IT WOULD BE WORKING FOR

6723
04:56:46,960 --> 04:56:49,280
THEM AND I RECOGNIZE YOU

6724
04:56:49,280 --> 04:56:51,880
PROBABLY AS YOU EXPLAIN SEE THE

6725
04:56:51,880 --> 04:56:57,560
EFFECT WOULD BE VARIABLE IN THE

6726
04:56:57,560 --> 04:56:58,440
ABSENCE OF GOOD INVESTIGATION

6727
04:56:58,440 --> 04:57:02,800
ANY QUANTIFICATION POTENTIALLY

6728
04:57:02,800 --> 04:57:05,320
COULD BE AFFECT OF THIS

6729
04:57:05,320 --> 04:57:06,640
TREATMENT OF THE DISEASE YOU ARE

6730
04:57:06,640 --> 04:57:12,600
TREATING, IT IS HARD TO SAY, I

6731
04:57:12,600 --> 04:57:14,120
WOULD BE INTERESTED TO HEARD

6732
04:57:14,120 --> 04:57:15,000
WHAT YOU HAVE TO SAY BECAUSE YOU

6733
04:57:15,000 --> 04:57:16,480
ARE USING IT. 

6734
04:57:16,480 --> 04:57:19,520
>>PRIMARILY IN CONTEXT OF
MY

6735
04:57:19,520 --> 04:57:22,080
RESEARCH PROJECT. WE SAY TO

6736
04:57:22,080 --> 04:57:24,240
PATIENTS THAT WE DON'T KNOW WHAT

6737
04:57:24,240 --> 04:57:29,640
THE AFFECTS ARE. THOSE WHO I AM

6738
04:57:29,640 --> 04:57:32,200
TREATING SO PEOPLE WHO VOLUNTEER

6739
04:57:32,200 --> 04:57:34,520
BUT WE FIND THEY DON'T MEET

6740
04:57:34,520 --> 04:57:38,160
CRITERIA FOR THE STUDY IF THEY

6741
04:57:38,160 --> 04:57:40,360
DON'T HAVE MEDICAL

6742
04:57:40,360 --> 04:57:42,960
CONTRAINDICATIONS WE ARE GIVING

6743
04:57:42,960 --> 04:57:46,800
THEM INCORRECTION FOR JUST AS A

6744
04:57:46,800 --> 04:57:51,720
COURTESY. PRIMARILY MY INTEREST

6745
04:57:51,720 --> 04:57:54,640
IS IN OUTCOMES RESEARCH, IT IS

6746
04:57:54,640 --> 04:57:56,640
WIDELY USED, IT IS VERY, VERY

6747
04:57:56,640 --> 04:58:05,200
WIDELY USED. IT SOUNDS LIKE IT

6748
04:58:05,200 --> 04:58:07,880
IS BASICALLY WOULD YOU SAY OFF

6749
04:58:07,880 --> 04:58:12,000
LABEL? THERE IS NOT A LABEL

6750
04:58:12,000 --> 04:58:13,080
>>YEAH.

6751
04:58:13,080 --> 04:58:16,000
>>NO CHARACTERIZATION.

6752
04:58:16,000 --> 04:58:20,640
>>I WAS ALWAYS TOLD THE
DEVICE

6753
04:58:20,640 --> 04:58:22,400
IS CLEARED DON'T GET IT BEYOND

6754
04:58:22,400 --> 04:58:26,560
THAT. IT MAKES IMPORTANT POINT

6755
04:58:26,560 --> 04:58:28,440
CHOCK RAN MADE ACCURATE POINT

6756
04:58:28,440 --> 04:58:30,720
PRP IS A LOT OF THAT DATA THAT

6757
04:58:30,720 --> 04:58:31,760
WORKS. AT THE SAME TIME THIS IS

6758
04:58:31,760 --> 04:58:33,800
USED, USED EVERYWHERE. NO DOUBT

6759
04:58:33,800 --> 04:58:38,560
TOO MUCH. PERHAPS OFTEN,

6760
04:58:38,560 --> 04:58:40,040
INDISCRIMINATELY, THE REALITY IT

6761
04:58:40,040 --> 04:58:42,000
IS USED. OKAY, THIS IS

6762
04:58:42,000 --> 04:58:42,680
ACCEPTABLE, THAT TRAIN LEFT THE

6763
04:58:42,680 --> 04:58:44,880
STATION.  HOW TO WE STILL

6764
04:58:44,880 --> 04:58:46,680
CONTINUE TO STUDY PRP IN OUR

6765
04:58:46,680 --> 04:58:50,080
CLINICAL TRIALS. RECOGNIZE WE

6766
04:58:50,080 --> 04:58:51,760
USE AS CONNIE SAID VERY WIDELY.

6767
04:58:51,760 --> 04:58:53,520
TAKING CARE OF ATHLETES I SEE IT

6768
04:58:53,520 --> 04:58:57,440
ALL THE TIME. THE EXPECTATION,

6769
04:58:57,440 --> 04:58:58,600
SPEND MORE TIME TALKING TO

6770
04:58:58,600 --> 04:58:59,840
AGENTS PLAYERS AND MANAGERS OUT

6771
04:58:59,840 --> 04:59:03,040
OF IT OR WHY WE DON'T KNOW WHAT

6772
04:59:03,040 --> 04:59:05,680
IT DOES. THAT IS THE CLINICAL

6773
04:59:05,680 --> 04:59:07,160
SIDE OF THINGS, IF YOU WANT TO

6774
04:59:07,160 --> 04:59:07,480
UNDERSTAND.

6775
04:59:07,480 --> 04:59:10,280
>>I UNDERSTAND
COMPLETELY. THAT

6776
04:59:10,280 --> 04:59:11,840
IS ANOTHER IN RESPONSE TO THE

6777
04:59:11,840 --> 04:59:15,880
QUESTIONS FOR THE ROUND TABLE.

6778
04:59:15,880 --> 04:59:18,760
IT IS A CERTAIN THINGS FOR USE

6779
04:59:18,760 --> 04:59:20,520
IN CLINICAL PRACTICE AND PEOPLE

6780
04:59:20,520 --> 04:59:21,760
HAVE NO IDEA WHAT THEY DO, WHAT

6781
04:59:21,760 --> 04:59:26,920
IS THE EFFICACY, I THINK WE OWE

6782
04:59:26,920 --> 04:59:29,320
THIS TO OUR PATIENTS, TO -- WHEN

6783
04:59:29,320 --> 04:59:32,080
WE GIVE THEM SOMETHING AS

6784
04:59:32,080 --> 04:59:33,200
TREATMENT WHEN WE PROMISE TO

6785
04:59:33,200 --> 04:59:37,040
TAKE CARE OF THEM AND HELP THEM

6786
04:59:37,040 --> 04:59:41,320
TO GIVE THEM PRODUCTS OR

6787
04:59:41,320 --> 04:59:42,640
TREATMENTS THAT ARE PROVEN

6788
04:59:42,640 --> 04:59:45,760
EFFECTIVE. WE ARE NOT HARMING

6789
04:59:45,760 --> 04:59:47,160
THEM.

6790
04:59:47,160 --> 04:59:50,080
>>AGREE.  THERE ARE SOME
HANDS

6791
04:59:50,080 --> 04:59:51,160
RAISED WE SHOULD GO THROUGH.

6792
04:59:51,160 --> 04:59:54,080
>>YES.

6793
04:59:54,080 --> 04:59:54,960
>>GEORGE.

6794
04:59:54,960 --> 04:59:57,080
>>FASCINATING DISCUSSION.
I WAS

6795
04:59:57,080 --> 04:59:58,600
TRYING TO DECIDE WHETHER CONNIE

6796
04:59:58,600 --> 05:00:01,480
WAS GOING TO GO TO JAIL OR NOT. 

6797
05:00:01,480 --> 05:00:06,560
SOMEWHERE THROUGH THIS PROCESS.

6798
05:00:06,560 --> 05:00:10,680
I'M WONDERING, I'M A CLINICIAN,

6799
05:00:10,680 --> 05:00:12,760
WE HAVE A PROGRAM JOINT

6800
05:00:12,760 --> 05:00:15,040
PRESERVATION CENTER WE DON'T

6801
05:00:15,040 --> 05:00:19,120
TALK ABOUT STEM CELLS, THAT PRP

6802
05:00:19,120 --> 05:00:20,920
PREPARATION IS APPROPRIATION OF

6803
05:00:20,920 --> 05:00:24,480
PATIENT OWN TISSUE. I DON'T

6804
05:00:24,480 --> 05:00:27,160
THINK PRP BEING IN A PRODUCT IS

6805
05:00:27,160 --> 05:00:28,600
THE DEVICE, IT IS THE PRODUCT

6806
05:00:28,600 --> 05:00:30,600
THEY OFFER, THE PROCESS TO

6807
05:00:30,600 --> 05:00:39,120
PREPARE THE PRP. AS AICALLY IN

6808
05:00:39,120 --> 05:00:40,760
ADDITION CLINICIANS CAN TAKE

6809
05:00:40,760 --> 05:00:41,760
SKIN FROM ONE PART OF THE

6810
05:00:41,760 --> 05:00:44,360
PATIENT BODY AND PUT IT IN

6811
05:00:44,360 --> 05:00:46,480
ANOTHER PART OF THE PATIENT BODY

6812
05:00:46,480 --> 05:00:47,400
AND TAKE FASCIA FROM ONE PART

6813
05:00:47,400 --> 05:00:49,280
AND USE IT FOR SOME OTHER

6814
05:00:49,280 --> 05:00:50,880
PURPOSE TO REPAIR ANOTHER TISSUE

6815
05:00:50,880 --> 05:00:52,120
AND ANOTHER PART OF THE PATIENT

6816
05:00:52,120 --> 05:00:56,640
BODY. LONG AS YOU ARE NOT NOT

6817
05:00:56,640 --> 05:00:59,680
MISROPINGSING WHAT YOU ARE DOING

6818
05:00:59,680 --> 05:01:04,120
AND WHY OR EXPERIMENTING WITH

6819
05:01:04,120 --> 05:01:08,120
THE INTENT GENERALIZABLE

6820
05:01:08,120 --> 05:01:09,600
INFORMATION, MY UNDERSTANDING AS

6821
05:01:09,600 --> 05:01:16,560
A CLINICIAN IS THIS IS PART OF

6822
05:01:16,560 --> 05:01:18,240
PRACTICE AND OUR OBLIGATION IS

6823
05:01:18,240 --> 05:01:19,880
TO BE STRAIGHT FORWARD AND

6824
05:01:19,880 --> 05:01:21,240
HONEST. IN OUR CASE WE HAVE A

6825
05:01:21,240 --> 05:01:23,400
REGISTRY, WE LOOK AT DATA, I

6826
05:01:23,400 --> 05:01:27,360
TELL PEOPLE THAT YOUR -- IF I

6827
05:01:27,360 --> 05:01:30,040
DID A KNEE REPLACEMENT WOULD BE

6828
05:01:30,040 --> 05:01:32,360
PROBABLY BETTER THAN PRP

6829
05:01:32,360 --> 05:01:34,240
INJECTION ON YOU BUT DATA

6830
05:01:34,240 --> 05:01:36,920
SUGGESTS SIX MONTHS AFTER PRP

6831
05:01:36,920 --> 05:01:38,000
INJECTION YOU ARE BETTER THAN

6832
05:01:38,000 --> 05:01:42,280
YOU ARE NOW WITH A HIGH

6833
05:01:42,280 --> 05:01:44,160
PROBABILITY, 80%. SO YOUR CHOICE

6834
05:01:44,160 --> 05:01:45,640
DELAYED SURGERY OR CONSIDER

6835
05:01:45,640 --> 05:01:47,400
USING THE PRP. THAT IS BASED ON

6836
05:01:47,400 --> 05:01:54,760
OUR OWN DATA.  I WILL NARROW

6837
05:01:54,760 --> 05:01:56,720
THIS JUST TO A QUESTION. IT IS

6838
05:01:56,720 --> 05:01:59,520
-- IS THERE A FRAMEWORK WITH FDA

6839
05:01:59,520 --> 05:02:03,800
THAT SAYS THIS IS A PART OF

6840
05:02:03,800 --> 05:02:05,400
PHYSICIAN PATIENT RELATIONSHIP

6841
05:02:05,400 --> 05:02:09,400
AND PHYSICIAN DISCRETION AND THE

6842
05:02:09,400 --> 05:02:12,800
PRIMARY PLACE YOU REGULATE IS

6843
05:02:12,800 --> 05:02:19,280
HOW PEOPLE DESCRIBE AND MARKET

6844
05:02:19,280 --> 05:02:20,760
RATHER THAN THE ACTUAL DELIVERY

6845
05:02:20,760 --> 05:02:24,080
OF PRP BY A PHYSICIAN.

6846
05:02:24,080 --> 05:02:26,560
>>I THINK YOU ACTUALLY
TOUCHED

6847
05:02:26,560 --> 05:02:29,240
UPON NUMBER OF TOPPINGS AND YOU

6848
05:02:29,240 --> 05:02:33,720
STARTED WITH SKIN TO SKIN OR

6849
05:02:33,720 --> 05:02:37,800
FASCIA FOR FASCIA. WHERE WILL IS

6850
05:02:37,800 --> 05:02:38,720
TRANSPORTATION OR RECONSTRUCTION

6851
05:02:38,720 --> 05:02:42,720
OF CLINICAL DEFECT. OR CORONARY

6852
05:02:42,720 --> 05:02:44,400
ARTERY BY SURGERY, TAKING

6853
05:02:44,400 --> 05:02:48,800
SOMEONE'S VEIN AND PUTTING IT

6854
05:02:48,800 --> 05:02:53,240
DIFFERENT PLACE TO HELP

6855
05:02:53,240 --> 05:02:55,840
CIRCULATION. THESE ARE THE TYPES

6856
05:02:55,840 --> 05:02:58,520
OF SITUATIONS WHERE OBVIOUSLY

6857
05:02:58,520 --> 05:03:01,720
THIS IS PART OF CLINICAL

6858
05:03:01,720 --> 05:03:05,360
PRACTICE AND THESE ARE TYPES OF

6859
05:03:05,360 --> 05:03:08,560
SITUATIONS WHERE THE TISSUE

6860
05:03:08,560 --> 05:03:10,880
WOULD APPLY. WHEN WE ARE TALKING

6861
05:03:10,880 --> 05:03:13,400
ABOUT GIVING SOME KIND OF

6862
05:03:13,400 --> 05:03:14,720
CELLULAR PREPARATION FOR THE

6863
05:03:14,720 --> 05:03:16,520
TREATMENT OF MEDICAL CONDITION,

6864
05:03:16,520 --> 05:03:20,920
IT IS AN ENTIRELY DIFFERENT

6865
05:03:20,920 --> 05:03:31,880
FRAMEWORFRAMEWORK COMPLETELY DIT

6866
05:03:31,880 --> 05:03:35,080
SITUATION FROM REGULATORY

6867
05:03:35,080 --> 05:03:39,240
PERSPECTIVE H. PRP PRODUCTS ARE

6868
05:03:39,240 --> 05:03:42,320
USED. AND THEY ARE USED IN

6869
05:03:42,320 --> 05:03:49,000
VARIOUS SETTINGS.  NUMBER OF

6870
05:03:49,000 --> 05:03:50,560
DEVICES THAT HAVE BEEN SENT TO

6871
05:03:50,560 --> 05:03:57,960
US AS APPLICATIONS FOR USE OF

6872
05:03:57,960 --> 05:04:06,720
PRP IN DIFFERENT SETTING SETTIN.

6873
05:04:06,720 --> 05:04:08,680
COUNSEL ONCE WE SEE

6874
05:04:08,680 --> 05:04:10,120
INVESTIGATIONS AND THE DEVICE IS

6875
05:04:10,120 --> 05:04:12,160
IN CLEARANCE AND APPROPRIATE

6876
05:04:12,160 --> 05:04:14,720
QUALIQUALITY. AS AS LONG AS THE

6877
05:04:14,720 --> 05:04:17,320
INVESTIGATIONS ARE ALSO ETHICAL

6878
05:04:17,320 --> 05:04:18,760
AND CONDUCTED APPROPRIATELY IN

6879
05:04:18,760 --> 05:04:22,960
THE INTEREST OF PATIENTS THIS IS

6880
05:04:22,960 --> 05:04:28,000
ONE PATHWAY WHERE PRP COULD

6881
05:04:28,000 --> 05:04:29,520
POTENTIALLY FALL INTO -- THIS IS

6882
05:04:29,520 --> 05:04:34,160
SOMETHING WE DO. THAT WAS

6883
05:04:34,160 --> 05:04:41,280
ANSWERS THE QUESTION. IS PATIENT

6884
05:04:41,280 --> 05:04:46,120
DOCTOR RELATIONSHIPS FROM THE

6885
05:04:46,120 --> 05:04:51,160
NOTION OF WELL CAN WE STEM CELLS

6886
05:04:51,160 --> 05:04:53,760
IN THE BATHROOM SOMEWHERE AND

6887
05:04:53,760 --> 05:04:55,640
UNDER THE PATIENT RELATIONSHIP

6888
05:04:55,640 --> 05:04:58,560
OFFER IT BECAUSE WE BELIEVE WE

6889
05:04:58,560 --> 05:05:02,120
WOULD WORK PRP. BECAUSE THAT IS

6890
05:05:02,120 --> 05:05:04,880
PATIENT DOCTOR RELATIONSHIPS CAN

6891
05:05:04,880 --> 05:05:08,600
INCLUDE LOT OF THINGS. AGAIN WE

6892
05:05:08,600 --> 05:05:11,400
OWE THIS TO OUR PATIENTS TO GIVE

6893
05:05:11,400 --> 05:05:12,720
THEM PRODUCTS THAT ARE BEST

6894
05:05:12,720 --> 05:05:15,600
QUALITY WE KNOW.

6895
05:05:15,600 --> 05:05:21,520
>>ANALOGOUS, THE
ANALOGOUS IS

6896
05:05:21,520 --> 05:05:23,760
ASPIRIN. ASPIRIN WE PRESCRIBE

6897
05:05:23,760 --> 05:05:27,560
ASPIRIN FOR LOTS OF THINGS AND

6898
05:05:27,560 --> 05:05:32,040
GRANTED THERE'S DATA BUT IF

6899
05:05:32,040 --> 05:05:34,560
ASPIRIN WAS ALREADY IN USE AND

6900
05:05:34,560 --> 05:05:37,200
ALREADY DOCUMENTED FOR LOTS OF

6901
05:05:37,200 --> 05:05:40,320
THINGS BUT FOR -- ANYWAY, THAT'S

6902
05:05:40,320 --> 05:05:44,720
A LITTLE STUFF. LET ME TURN

6903
05:05:44,720 --> 05:05:45,400
THINGS OVER TO SHANE.

6904
05:05:45,400 --> 05:05:46,280
>>SHANE, YES.

6905
05:05:46,280 --> 05:05:49,640
>>I WANTED TO GO BACK TO
THAT

6906
05:05:49,640 --> 05:05:52,200
CONVERSATION THAT WE HAVE WITH

6907
05:05:52,200 --> 05:05:54,040
PATIENTS AND HOW IMPORTANT AND

6908
05:05:54,040 --> 05:05:55,480
VALUABLE AND HOW IN THAT

6909
05:05:55,480 --> 05:05:58,080
DISCUSSION AND SHARED DECISION

6910
05:05:58,080 --> 05:06:02,960
MAKING, WE COMMONLY DON'T

6911
05:06:02,960 --> 05:06:04,520
EXPLAIN MANY TREATMENTS, NO

6912
05:06:04,520 --> 05:06:07,600
PATIENT ASKS HOW TYLENOL WORKS

6913
05:06:07,600 --> 05:06:10,400
TO RELIEVE PAIN. THAT IS

6914
05:06:10,400 --> 05:06:12,160
SOMEWHAT WHAT GEORGE IS SAYING

6915
05:06:12,160 --> 05:06:15,240
WITH ASPIRIN. WE BELIEVE PRP HAS

6916
05:06:15,240 --> 05:06:18,680
A THERAPEUTICS AFFECT AND I ALSO

6917
05:06:18,680 --> 05:06:21,240
WANTED TO AT LEAST HIGH LIGHT

6918
05:06:21,240 --> 05:06:23,040
THERE MAYBE A LITTLE

6919
05:06:23,040 --> 05:06:25,680
DISAGREEMENT IN THE PANEL AND IN

6920
05:06:25,680 --> 05:06:27,880
TERMS OF STATE OF THE CURRENT

6921
05:06:27,880 --> 05:06:29,640
EVIDENCE BECAUSE THERE'S BEEN A

6922
05:06:29,640 --> 05:06:31,960
NUMBER OF WELL DESIGNED TRIALS

6923
05:06:31,960 --> 05:06:33,400
NOT ALL WHICH ARE POSITIVE

6924
05:06:33,400 --> 05:06:36,040
CERTAINLY SOME OF WHICH ARE

6925
05:06:36,040 --> 05:06:41,800
NEGATIVE BUT DO -- HAVE BEEN

6926
05:06:41,800 --> 05:06:45,360
ANALYZED SYSTEMATICALLY AND META

6927
05:06:45,360 --> 05:06:48,320
ANALYSES TO SEE THERE IS A

6928
05:06:48,320 --> 05:06:50,000
THERAPEUTIC EFFECT AND SYMPTOM

6929
05:06:50,000 --> 05:06:53,280
MODIFYING EFFECT FOR PRP. THAT

6930
05:06:53,280 --> 05:06:55,720
SAME EVIDENCE DOESN'T EXIST

6931
05:06:55,720 --> 05:06:57,960
NUMBER OF THE OTHER BIOLOGICS

6932
05:06:57,960 --> 05:06:59,720
DISCUSSED TODAY, THERE IS A

6933
05:06:59,720 --> 05:07:01,720
REASONABLE EVIDENCE BASED TO

6934
05:07:01,720 --> 05:07:03,320
HAVE THAT CONVERSATION WITH

6935
05:07:03,320 --> 05:07:07,520
PATIENTS SO THAT BRINGS BACK

6936
05:07:07,520 --> 05:07:09,160
AMYE TO THE CONVERSATION AND

6937
05:07:09,160 --> 05:07:11,800
PATIENT ADVOCACY COLLEAGUES

6938
05:07:11,800 --> 05:07:12,600
BECAUSE WHEN WE HAVE THESE

6939
05:07:12,600 --> 05:07:13,920
CONVERSATIONS WITH PATIENTS THIS

6940
05:07:13,920 --> 05:07:16,600
IS SOMETHING MY GROUP STUDY

6941
05:07:16,600 --> 05:07:18,800
EXTENSIVELY WITH MY BIOETHICAL

6942
05:07:18,800 --> 05:07:20,280
COMPLYINGS IN TERMS OF WHAT IS

6943
05:07:20,280 --> 05:07:22,160
THE PATIENT UNDERSTANDING OF HOW

6944
05:07:22,160 --> 05:07:23,640
BIOLOGIC THERAPIES WORK AND

6945
05:07:23,640 --> 05:07:26,880
PATIENTS THAT COMING IN M AS DR.

6946
05:07:26,880 --> 05:07:29,920
RODEO SAID, ATHLETES, LOOKING

6947
05:07:29,920 --> 05:07:31,520
FOR THESE TREATMENT, WHAT CAN

6948
05:07:31,520 --> 05:07:33,520
THEIR UNDERSTANDING AND CAN THEY

6949
05:07:33,520 --> 05:07:36,440
EVEN UNDERSTAND THE BIOLOGY WE

6950
05:07:36,440 --> 05:07:37,720
ARE ALL TALKING ABOUT HERE

6951
05:07:37,720 --> 05:07:40,320
ENOUGH TO GIVE INFORMED CONSENT

6952
05:07:40,320 --> 05:07:42,520
FOR TREATMENT OF THIS. THESE ARE

6953
05:07:42,520 --> 05:07:44,120
COMPLEX CONVERSATIONS THAT EVEN

6954
05:07:44,120 --> 05:07:46,240
IF WE DID KNOW EXACT MOLECULAR

6955
05:07:46,240 --> 05:07:48,400
MECHANISM OF HOW PRP RELIEVED

6956
05:07:48,400 --> 05:07:49,600
PAIN, IT IS UNLIKELY PATIENTS

6957
05:07:49,600 --> 05:07:53,040
WOULD BE ABLE TO UNDERSTAND IT

6958
05:07:53,040 --> 05:07:55,160
ENOUGH FROM INFORMED CONSENT

6959
05:07:55,160 --> 05:07:56,880
STANDPOINT. THAT IS THE JOB OF

6960
05:07:56,880 --> 05:08:01,600
THE CLINICIAN TO SYNTHESIZE IN

6961
05:08:01,600 --> 05:08:02,680
THE CLINICAL EVIDENCE AND THEN

6962
05:08:02,680 --> 05:08:05,760
BRING IT DOWN TO LEVEL OF

6963
05:08:05,760 --> 05:08:06,960
PATIENT UNDERSTANDING SO YOU CAN

6964
05:08:06,960 --> 05:08:09,200
HAVE APPROPRIATE INFORM CONSENT,

6965
05:08:09,200 --> 05:08:11,040
IT IS OUR JOB HERE IN THIS GROUP

6966
05:08:11,040 --> 05:08:12,920
AND PANEL AND SCIENTIFIC

6967
05:08:12,920 --> 05:08:14,880
COMMUNITY TO FIGURE HOW IT IS

6968
05:08:14,880 --> 05:08:17,000
THEY WORK. THAT IS DIFFERENT

6969
05:08:17,000 --> 05:08:17,920
THAN HOW WE TALK TO OUR

6970
05:08:17,920 --> 05:08:24,000
PATIENTS.  THANK YOU. CRITICALLY

6971
05:08:24,000 --> 05:08:25,840
IMPORTANT ON WHICH PATIENT,

6972
05:08:25,840 --> 05:08:28,640
WHICH IS MOST LIKELY TO BENEFIT

6973
05:08:28,640 --> 05:08:30,200
BECAUSE WE ALL HAVE SEEN

6974
05:08:30,200 --> 05:08:32,680
PATIENTS WHO HAVE IMPROVED

6975
05:08:32,680 --> 05:08:37,640
FOLLOWING PRP TREATMENT BUT IT

6976
05:08:37,640 --> 05:08:41,120
ISN'T EVERYONE. GOING BACK TO --

6977
05:08:41,120 --> 05:08:45,760
SO NOBODY THINKS THAT'S AN --

6978
05:08:45,760 --> 05:08:47,400
BATS AN EYE ABOUT THE LONG

6979
05:08:47,400 --> 05:08:49,960
HISTORY OF CORTICOSTEROID

6980
05:08:49,960 --> 05:08:52,320
INJECTIONS. THAT IS ALMOST IN

6981
05:08:52,320 --> 05:08:55,320
PRIMARY CARE, THAT IS ALMOST THE

6982
05:08:55,320 --> 05:08:57,760
FIRST LINE INJECTION TREATMENT

6983
05:08:57,760 --> 05:09:02,040
BUT EVEN GOING BACK TO DR.

6984
05:09:02,040 --> 05:09:03,960
HINCH'S WORK, CLEARLY VERY

6985
05:09:03,960 --> 05:09:06,600
CLEARLY IN HIS ORIGINAL PAPER

6986
05:09:06,600 --> 05:09:10,600
FROM HIS NOBEL PRIZE HE SAYS IT

6987
05:09:10,600 --> 05:09:11,120
DOESN'T ALWAYS HELP IN

6988
05:09:11,120 --> 05:09:16,360
OSTEOARTHRITIS.  THAT REFLECTS

6989
05:09:16,360 --> 05:09:19,240
THE DIVERSITY OF OA DISEASE

6990
05:09:19,240 --> 05:09:23,080
STATES WHICH WE HAVE TALKED

6991
05:09:23,080 --> 05:09:24,320
ABOUT VERY IMPORTANT, IT IS

6992
05:09:24,320 --> 05:09:28,400
SOMETHING I DO CLARIFY WITH MY

6993
05:09:28,400 --> 05:09:33,960
PATIENTS THAT I -- IT IS NOT THE

6994
05:09:33,960 --> 05:09:36,320
DATA SHOWS OVERALL SO I CAN

6995
05:09:36,320 --> 05:09:42,800
SPEAK ON MY OWN DATA HAS, I SHOW

6996
05:09:42,800 --> 05:09:44,360
MAIN BENEFIT. NOT EVERYBODY HAS

6997
05:09:44,360 --> 05:09:49,000
IMPROVED.  THEY HEAR THAT. MOST

6998
05:09:49,000 --> 05:09:51,600
PEOPLE COMING IN, SCOTT

6999
05:09:51,600 --> 05:09:52,520
MENTIONED, THEY HAVE GOT ONE

7000
05:09:52,520 --> 05:09:55,360
THING ON THEIR MIND, I THINK

7001
05:09:55,360 --> 05:09:56,960
THAT THE PRP WILL BE BETTER THAN

7002
05:09:56,960 --> 05:10:05,640
THE OTHER INJECTIONS ALREADY. IF

7003
05:10:05,640 --> 05:10:07,240
A NUMBER OF THEM COME BACK VERY

7004
05:10:07,240 --> 05:10:09,560
HAPPY BUT IT IS NOT EVERYONE AND

7005
05:10:09,560 --> 05:10:13,840
IT IS OUR JOB TO FIGURE OUT TO

7006
05:10:13,840 --> 05:10:16,880
BETTER DEFINE DIFFERENT OA

7007
05:10:16,880 --> 05:10:18,320
DISEASE STATES AND WITH

7008
05:10:18,320 --> 05:10:18,880
THERAPYINGS MAY BE MORE

7009
05:10:18,880 --> 05:10:24,040
APPROPRIATE. FOR PEOPLE IN

7010
05:10:24,040 --> 05:10:26,800
DIFFERENT STATES OF DISEASE. --

7011
05:10:26,800 --> 05:10:28,480
THERAPIES.

7012
05:10:28,480 --> 05:10:30,120
>>I'M SORRY, GO AHEAD
AMYE. 

7013
05:10:30,120 --> 05:10:33,800
>>I WANT TO ADD TO THIS

7014
05:10:33,800 --> 05:10:37,160
CONVERSATION ABOUT STEM CELLS

7015
05:10:37,160 --> 05:10:39,200
AND PRP FROM THE PATIENT ANGLE.

7016
05:10:39,200 --> 05:10:43,760
HEARING TODAY, I THINK THE ONE

7017
05:10:43,760 --> 05:10:47,680
PIECE OF INFORMATION I BELIEVE

7018
05:10:47,680 --> 05:10:49,480
MARK INDICATED IS THAT DOD, THE

7019
05:10:49,480 --> 05:10:52,160
VA, ARTHRITIS FOUNDATION AND

7020
05:10:52,160 --> 05:10:54,280
AMERICAN COLLEGE OF RHEUMATOLOGY

7021
05:10:54,280 --> 05:10:56,720
EACH HAVE PUT OUT GUIDELINES

7022
05:10:56,720 --> 05:10:59,840
THAT SAY NOT RECOMMENDED.  I

7023
05:10:59,840 --> 05:11:05,000
FOUND THAT SHOCKING IN THE SENSE

7024
05:11:05,000 --> 05:11:08,000
OF NUMBER ONE, CONSISTENCY AND

7025
05:11:08,000 --> 05:11:09,000
PROMPTED ME PROBABLY 25

7026
05:11:09,000 --> 05:11:09,640
QUESTIONS WHEN THE LAST TIME

7027
05:11:09,640 --> 05:11:16,240
THIS WAS DONE, THIS IS A

7028
05:11:16,240 --> 05:11:17,440
EMERGING FIELD, WHAT ARE

7029
05:11:17,440 --> 05:11:21,680
PATIENTS ASKING IN PARTICULAR.

7030
05:11:21,680 --> 05:11:26,320
IN MY EXPERIENCE IT COMES TO

7031
05:11:26,320 --> 05:11:26,960
TRUST BETWEEN CLINICIAN AND

7032
05:11:26,960 --> 05:11:35,200
PATIENT. A TYPICAL QUESTION I AM

7033
05:11:35,200 --> 05:11:36,760
ASKED AS IF I WERE THE HEALTH

7034
05:11:36,760 --> 05:11:38,360
CLINICIAN. IF I WERE YOUR

7035
05:11:38,360 --> 05:11:39,120
DAUGHTER WOULD YOU RECOMMEND

7036
05:11:39,120 --> 05:11:41,000
THIS TO YOUR DAUGHTER, WOULD YOU

7037
05:11:41,000 --> 05:11:44,080
RECOMMEND IT TO ME. DIDN'T COME

7038
05:11:44,080 --> 05:11:47,040
DOWN TO PROCESS, EQUIPMENT,

7039
05:11:47,040 --> 05:11:49,560
THERE WAS AN ASSUMPTION AND A

7040
05:11:49,560 --> 05:11:53,680
HUGE LEAP ABOUT WELL, IT IS MY

7041
05:11:53,680 --> 05:11:56,400
BLOOD. THEREFORE MUST BE OKAY. 

7042
05:11:56,400 --> 05:11:58,840
SPIN OUT THE BAD STUFF AND KEEP

7043
05:11:58,840 --> 05:12:00,080
THE GOOD STUFF AND THAT WILL

7044
05:12:00,080 --> 05:12:07,520
HELP ME. WE DO THE COLLECTIVE WE

7045
05:12:07,520 --> 05:12:09,000
BECAUSE I DON'T AGREE WITH IT,

7046
05:12:09,000 --> 05:12:10,800
IT IS ALL GOING TO GO -- COME

7047
05:12:10,800 --> 05:12:12,160
FROM AND GO BACK TO THE

7048
05:12:12,160 --> 05:12:19,080
CLINICIAN. MAKING SURE A BODY

7049
05:12:19,080 --> 05:12:23,640
LIKE THIS AT NIAMS WORKING WITH

7050
05:12:23,640 --> 05:12:26,920
THE FDA HOW IS THE BEST WAY

7051
05:12:26,920 --> 05:12:28,320
COCHARACTERIZE THIS, TO LOOK AT

7052
05:12:28,320 --> 05:12:29,360
THE DIFFERENT IMPORTANT ASPECTS

7053
05:12:29,360 --> 05:12:33,680
OF THAT TO LOOK FOR CONSISTENCY

7054
05:12:33,680 --> 05:12:34,760
LONGEVITY, QUALITY, ALL THINGS

7055
05:12:34,760 --> 05:12:37,840
WE HAVE BEEN TALKING ABOUT TODAY

7056
05:12:37,840 --> 05:12:43,720
ARE INSTILLED INTO THIS ONE

7057
05:12:43,720 --> 05:12:45,440
PARTICULAR POTENTIAL, IT HAS A

7058
05:12:45,440 --> 05:12:47,120
LIFE OUTSIDE THE OFFICE KIND OF

7059
05:12:47,120 --> 05:12:51,680
SCENARIO.  IS I DON'T WANT TO

7060
05:12:51,680 --> 05:12:55,320
SAY CONTAINED BUT MANAGED FROM

7061
05:12:55,320 --> 05:12:57,320
SYSTEMATIC PROCESS, DR. CHU,

7062
05:12:57,320 --> 05:12:59,400
CONNIE WAS TALKING ABOUT, TO BE

7063
05:12:59,400 --> 05:13:00,720
SYSTEMATIC. I THINK THAT IS THE

7064
05:13:00,720 --> 05:13:06,880
MOST IMPORTANT THING. WOULD I

7065
05:13:06,880 --> 05:13:08,880
GET IT? THE WAY I FEEL LIKE NOW,

7066
05:13:08,880 --> 05:13:14,680
NO.

7067
05:13:14,680 --> 05:13:15,360
>>ASK ME NEXT MONTH.

7068
05:13:15,360 --> 05:13:16,440
>>THANK YOU, THIS IS
IMPORTANT

7069
05:13:16,440 --> 05:13:18,120
FOR ALL OF US TO HEAR. BECAUSE

7070
05:13:18,120 --> 05:13:22,400
IF WE WERE TO PROPOSE OR OFFER

7071
05:13:22,400 --> 05:13:26,920
TREATMENTS TO PATIENTS WE WANT

7072
05:13:26,920 --> 05:13:27,640
TO AT LEAST SEE GOOD CLINICAL

7073
05:13:27,640 --> 05:13:28,760
TRIALS DONE WITH THESE

7074
05:13:28,760 --> 05:13:29,880
TREATMENTS, DEMONSTRATING THAT

7075
05:13:29,880 --> 05:13:32,040
THE TREATMENTS ARE EFFECTIVE.

7076
05:13:32,040 --> 05:13:34,160
AND THEY'D ARE SAFE. ANECDOTAL

7077
05:13:34,160 --> 05:13:35,800
CASES OF EFFECTIVENESS EXIST

7078
05:13:35,800 --> 05:13:40,280
WITH EVERYTHING. INCLUDING

7079
05:13:40,280 --> 05:13:43,200
NORMAL SALINE BUT WHEN WE OFFER

7080
05:13:43,200 --> 05:13:44,960
AGAIN TREATMENTS PARTICULARLY

7081
05:13:44,960 --> 05:13:46,360
INJECTABLE TO PEOPLE WE NEED TO

7082
05:13:46,360 --> 05:13:47,960
MAKE SURE THEY ARE EFFECTIVE AND

7083
05:13:47,960 --> 05:13:49,920
WE CAN'T MAKE SURE THEY ARE

7084
05:13:49,920 --> 05:13:50,800
EFFECTIVE BASED ON THE EVIDENCE

7085
05:13:50,800 --> 05:13:55,880
THAT IS OUT THERE THAT'S

7086
05:13:55,880 --> 05:13:57,320
CONTROVERSIAL OPEN LABEL EARLY

7087
05:13:57,320 --> 05:14:00,960
STUDIES SMALL STUDIES. MANY CASE

7088
05:14:00,960 --> 05:14:03,840
SERIOUS, WE NEED GOOD TRIALS,

7089
05:14:03,840 --> 05:14:05,000
THAT IS ANOTHER I GUESS -- GAP

7090
05:14:05,000 --> 05:14:07,000
IN THE FIELD WHEN YOU PUT TRIALS

7091
05:14:07,000 --> 05:14:12,600
AND QUALITYVA QUALITY INVESTIGAO

7092
05:14:12,600 --> 05:14:13,600
SHOW WHATEVER PRODUCT WE BELIEVE

7093
05:14:13,600 --> 05:14:17,360
HAVE POTENTIAL, GREAT POTENTIAL

7094
05:14:17,360 --> 05:14:22,360
IN THEIR APPLICATION REALLY

7095
05:14:22,360 --> 05:14:24,000
UPHOLD TO THE LEVEL OF EVIDENCE

7096
05:14:24,000 --> 05:14:26,400
WE ARE WORKING FOR AND LEVEL OF

7097
05:14:26,400 --> 05:14:28,000
BENEFIT PATIENTS ARE WORKING FOR

7098
05:14:28,000 --> 05:14:34,640
IN THESE PRODUCTS.

7099
05:14:34,640 --> 05:14:36,520
 A GOOD SEGUE TALKING
ABOUT

7100
05:14:36,520 --> 05:14:40,720
THE DISCUSSION, THE FIRST

7101
05:14:40,720 --> 05:14:43,680
DISCUSSION QUESTION IS A HUGE

7102
05:14:43,680 --> 05:14:44,600
QUESTION WHAT EVIDENCE SUPPORTS

7103
05:14:44,600 --> 05:14:48,680
SAFETY AND EFFICACY OF THE

7104
05:14:48,680 --> 05:14:54,280
CLINICAL USE STATES OF THE ART

7105
05:14:54,280 --> 05:14:55,720
REGENERATIVE THERAPY FOR KNEE

7106
05:14:55,720 --> 05:14:58,600
OA. THIS PARTICULAR QUESTION IS

7107
05:14:58,600 --> 05:14:59,840
EXTREMELY LARGE BUT OUR

7108
05:14:59,840 --> 05:15:02,600
DISCUSSION UP TO THIS POINT ON

7109
05:15:02,600 --> 05:15:05,360
PLATELET RICH PLASMA IS COVERED

7110
05:15:05,360 --> 05:15:11,640
SOME OF THE ANGLES AND I AM

7111
05:15:11,640 --> 05:15:16,880
GOING TO PUT OUT THAT I WOULD

7112
05:15:16,880 --> 05:15:22,280
FAVOR MAYBE A LITTLE BIT

7113
05:15:22,280 --> 05:15:23,360
ADDITIONAL DISCUSSION ON THIS

7114
05:15:23,360 --> 05:15:24,960
BUT SPENDING MORE TIME ON WHAT

7115
05:15:24,960 --> 05:15:27,800
ARE THE EMERGING AND --

7116
05:15:27,800 --> 05:15:30,520
QUESTIONS 2 AND 3.

7117
05:15:30,520 --> 05:15:31,200
TALKING ABOUT EMERGING

7118
05:15:31,200 --> 05:15:32,960
APPROACHES IN AREAS OF RESEARCH

7119
05:15:32,960 --> 05:15:34,480
OFFERING NEW OPPORTUNITIES FOR

7120
05:15:34,480 --> 05:15:37,240
CARTILAGE PRESERVATION AND

7121
05:15:37,240 --> 05:15:42,040
RESTORATION IN KNEE OA. I WOULD

7122
05:15:42,040 --> 05:15:44,880
FAVOR SPENDING MORE TIME ON THAT

7123
05:15:44,880 --> 05:15:51,080
BECAUSE OVERALL SUMMATION OF

7124
05:15:51,080 --> 05:15:53,560
CLINICAL EVIDENCE FOR MOST

7125
05:15:53,560 --> 05:15:55,440
COMMON ORTHO BIOLOGICS AS WE

7126
05:15:55,440 --> 05:15:58,960
HAVE DISCUSSED WITH PRP VERY,

7127
05:15:58,960 --> 05:16:02,320
VERY IMPERFECT AND PRP TREATMENT

7128
05:16:02,320 --> 05:16:07,120
OF KNEE OA AS DR. SHAPIRO

7129
05:16:07,120 --> 05:16:08,960
MENTIONED HAS ARGUABLY THE

7130
05:16:08,960 --> 05:16:13,560
LARGEST BODY OF EVIDENCE.  I

7131
05:16:13,560 --> 05:16:21,640
WILL THROW OUT MY OPINION HOW

7132
05:16:21,640 --> 05:16:22,280
MUCH TIME WE SHOULD SPEND ON

7133
05:16:22,280 --> 05:16:23,440
THIS AND WHETHER TO MOVE TO THE

7134
05:16:23,440 --> 05:16:24,080
NEXT QUESTION.

7135
05:16:24,080 --> 05:16:26,240
>>AGREE, CONNIE, WE SPENT
A LOT

7136
05:16:26,240 --> 05:16:27,800
OF TIME ON QUESTION ONE, SAFETY

7137
05:16:27,800 --> 05:16:31,240
AND EFFICACY, I THINK WE CAN ONE

7138
05:16:31,240 --> 05:16:36,400
PART PUT IT TO BED.  SAFETY,

7139
05:16:36,400 --> 05:16:39,760
MOST AUTOLOGOUS SEEM TO BE SAFE.

7140
05:16:39,760 --> 05:16:40,600
SO SECOND PART OF THE QUESTION

7141
05:16:40,600 --> 05:16:43,920
IS WHERE WE NEED DATA EVE DA

7142
05:16:43,920 --> 05:16:45,280
SCHISM WHAT SUPPORTS EFFICACY OF

7143
05:16:45,280 --> 05:16:47,320
AT LEAST OF THESE THERAPIES. WE

7144
05:16:47,320 --> 05:16:49,680
CAN DISCUSS THAT THE LAST FOUR

7145
05:16:49,680 --> 05:16:50,640
OR FIVE HOURS DATA IS THERE,

7146
05:16:50,640 --> 05:16:56,760
MIXED AT BEST. MODEST AT BEST. 

7147
05:16:56,760 --> 05:16:58,080
QUESTIONS TWO AND THREE, IF

7148
05:16:58,080 --> 05:16:59,520
SOMEONE CAN PUT THEM IN THE

7149
05:16:59,520 --> 05:17:02,080
CHAT, THE MEAT OF THE

7150
05:17:02,080 --> 05:17:03,400
DISCUSSION. AS FAR AS PLANNING

7151
05:17:03,400 --> 05:17:05,720
MOVING FORWARD. EMERGING

7152
05:17:05,720 --> 05:17:06,560
APPROACHESES IN YARRS OF

7153
05:17:06,560 --> 05:17:08,360
RESEARCH OFFERING NEW

7154
05:17:08,360 --> 05:17:10,560
OPPORTUNITIES. WE DISCUSS,

7155
05:17:10,560 --> 05:17:13,040
EXOSOMES OR GENE THERAPY OR

7156
05:17:13,040 --> 05:17:16,240
APPROACHES WE HAVE HEARD NOVEL

7157
05:17:16,240 --> 05:17:17,280
APPROACHES, HAVE A DISCUSSION

7158
05:17:17,280 --> 05:17:20,040
HOW WE MOVE FORWARD TO FURTHER

7159
05:17:20,040 --> 05:17:21,480
EVALUATE THESE INNOVATIVE OR

7160
05:17:21,480 --> 05:17:28,680
EMERGING APPROACHES.  WE PRPs

7161
05:17:28,680 --> 05:17:31,080
IN CELLS PRETTY GOOD NOT THAT

7162
05:17:31,080 --> 05:17:32,040
THERE AREN'T OUTSTANDING

7163
05:17:32,040 --> 05:17:33,520
QUESTIONS BUT WHAT IS NEXT ON

7164
05:17:33,520 --> 05:17:34,560
THE HORIZON?

7165
05:17:34,560 --> 05:17:36,600
>>YEAH. SHOULD WE TALK --

7166
05:17:36,600 --> 05:17:39,120
SHOULD WE FLIP THAT AND ACTUALLY

7167
05:17:39,120 --> 05:17:41,400
TALK ABOUT BECAUSE WE ARE

7168
05:17:41,400 --> 05:17:42,160
TALKING ABOUT CLINICAL

7169
05:17:42,160 --> 05:17:48,760
EVALUATION. SO OR WE CAN JUST GO

7170
05:17:48,760 --> 05:17:50,840
IN ORDER BUT REALLY THERE ARE

7171
05:17:50,840 --> 05:17:58,200
CHALLENGES AND GAPS, IN THE

7172
05:17:58,200 --> 05:17:59,440
CLINICAL EVALUATION OF CLINICAL

7173
05:17:59,440 --> 05:18:01,440
OUTCOMES THAT IS A MAJOR

7174
05:18:01,440 --> 05:18:03,680
IMPEDIMENT TO US HAVING THE

7175
05:18:03,680 --> 05:18:05,320
EVIDENCE WE NEED TO BASE OUR

7176
05:18:05,320 --> 05:18:13,680
TREATMENT DECISI DECISIONS BUT N

7177
05:18:13,680 --> 05:18:15,920
ORDER TO QUESTION TWO. DOES

7178
05:18:15,920 --> 05:18:19,800
JENNIFER, DID YOU HAVE SOMETHING

7179
05:18:19,800 --> 05:18:20,760
TO SAY?

7180
05:18:20,760 --> 05:18:22,960
>>I WANT TO BRING UP A
POINT

7181
05:18:22,960 --> 05:18:25,920
THAT POTENTIALLY RELEVANT FOR

7182
05:18:25,920 --> 05:18:28,680
ALL THEM. T WE TALKED TODAY

7183
05:18:28,680 --> 05:18:31,680
ABOUT UNDERSTANDING THERAPEUTIC

7184
05:18:31,680 --> 05:18:32,400
MECHANISMS, BETTER CLINICAL

7185
05:18:32,400 --> 05:18:36,600
TRIALS BETTER THERAPIES. IT IS

7186
05:18:36,600 --> 05:18:38,360
STILL GENERAL THERAPIES THAT WE

7187
05:18:38,360 --> 05:18:40,000
THINK ABOUT, FIELDS SUCH AS

7188
05:18:40,000 --> 05:18:41,520
CANCER HAVE COMBINATION

7189
05:18:41,520 --> 05:18:44,360
THERAPIES THAT ARE REALLY MAKE A

7190
05:18:44,360 --> 05:18:47,600
HUGE DIFFERENCE, THINKING ABOUT

7191
05:18:47,600 --> 05:18:50,760
CELLS IN IMMUNE SYSTEM HANDLE

7192
05:18:50,760 --> 05:18:51,840
IMMUNE STROMAL COMMUNICATION

7193
05:18:51,840 --> 05:18:55,200
WHETHER IT BE STEM CELLS, OTHER

7194
05:18:55,200 --> 05:18:57,360
STROMAL PARTS THEN TALK IMMUNE

7195
05:18:57,360 --> 05:18:59,040
RESPONSE. WE HAVE SHOWN THIS

7196
05:18:59,040 --> 05:19:00,280
POSITIVE FEEDBACK LOOP YOU CAN

7197
05:19:00,280 --> 05:19:03,240
HIT ONE BUT THEN NOT -- THEY ARE

7198
05:19:03,240 --> 05:19:05,240
GOING TO FORM BECAUSE YOU ARE

7199
05:19:05,240 --> 05:19:06,240
NOT HITTING BOTH OF THE

7200
05:19:06,240 --> 05:19:10,080
PATHWAYS.  I REELIZE THIS

7201
05:19:10,080 --> 05:19:11,960
INCREASES COMPLEXITY OF CLINICAL

7202
05:19:11,960 --> 05:19:14,000
TRIALS AND IF I BRING IT UP TO

7203
05:19:14,000 --> 05:19:16,080
PEOPLE THEY JUST SAY IT IS NOT

7204
05:19:16,080 --> 05:19:18,360
POSSIBLE TO DO THIS TYPE OF

7205
05:19:18,360 --> 05:19:20,080
TRIAL REGULATORY PATHWAYS TOO

7206
05:19:20,080 --> 05:19:22,800
DIFFICULT BUT I THINK IT IS

7207
05:19:22,800 --> 05:19:23,760
POTENTIALLY CRITICAL FOR THE

7208
05:19:23,760 --> 05:19:29,400
FIELD. 

7209
05:19:29,400 --> 05:19:33,120
>>THANK YOU, DEFINITELY
AGREE.

7210
05:19:33,120 --> 05:19:37,960
WITH SOMETHING COMPLEX AS OA, WE

7211
05:19:37,960 --> 05:19:40,880
NEED TO TAKE A SYSTEMS BASED

7212
05:19:40,880 --> 05:19:43,360
APPROACH, JOHNNY HAS DONE SOME

7213
05:19:43,360 --> 05:19:45,720
CLINICAL TRIALS WHERE HE TRIED

7214
05:19:45,720 --> 05:19:48,040
TO DO SOME COMBINATION THERAPIES

7215
05:19:48,040 --> 05:19:58,440
AND HE HAS HIS HAND UP.

7216
05:20:01,040 --> 05:20:03,760
>>I AGREE WITH JENNIFER,
WE

7217
05:20:03,760 --> 05:20:05,200
TALK ABOUT CARTILAGE BUT I THINK

7218
05:20:05,200 --> 05:20:07,840
A LOT OF WORK BEING DONE AT

7219
05:20:07,840 --> 05:20:12,160
CELLULAR SENESCENCE HAVE SHOWN

7220
05:20:12,160 --> 05:20:14,760
SENESCENCE CELLS ARE DETRIMENTAL

7221
05:20:14,760 --> 05:20:15,960
FOR CARTILAGE AND MAYBE IN THIS

7222
05:20:15,960 --> 05:20:17,800
CASE ELIMINATE THEM AND THIS IS

7223
05:20:17,800 --> 05:20:19,880
KIND OF WHEN WE THINK ABOUT

7224
05:20:19,880 --> 05:20:21,760
(INAUDIBLE) WE THINK ABOUT PRP

7225
05:20:21,760 --> 05:20:29,240
OR BMAC OR STEM CELLS SINOLITIC

7226
05:20:29,240 --> 05:20:31,360
DRUGS CAN BE USED TO SENESCENCE

7227
05:20:31,360 --> 05:20:33,600
CELLS. THEY DON'T HAVE TO BE USE

7228
05:20:33,600 --> 05:20:35,600
ALONE, THEY CAN BE USED IN

7229
05:20:35,600 --> 05:20:37,640
CONJUNCTION WITH STEM CELLS. AND

7230
05:20:37,640 --> 05:20:40,640
ALSO I WANTED TO SAY FIBROSIS

7231
05:20:40,640 --> 05:20:43,320
HAS BEEN A BIG PROBLEM FOR

7232
05:20:43,320 --> 05:20:48,400
SKELETAL MUSCLE BUT TURNS OUT

7233
05:20:48,400 --> 05:20:50,920
CARTILAGE REPAIR LEAD TO FIBER

7234
05:20:50,920 --> 05:20:52,600
CARTILAGER WE THINK IS FIBROSIS

7235
05:20:52,600 --> 05:20:57,960
AND CARTILAGE NOW APPROACH BLOCK

7236
05:20:57,960 --> 05:21:01,160
TGF BETA 1 REDUCE TGF BETA 1 NOT

7237
05:21:01,160 --> 05:21:02,680
ELIMINATE BUT REDUCE IT IN

7238
05:21:02,680 --> 05:21:05,120
CARTILAGE REPAIR. SO WHAT WE

7239
05:21:05,120 --> 05:21:07,120
HAVE STARTED, IN THE CLINIC, I

7240
05:21:07,120 --> 05:21:10,400
WANT TO MAKE FINAL POINT ABOUT

7241
05:21:10,400 --> 05:21:12,840
THE FACT WHEN A PATIENT COME AND

7242
05:21:12,840 --> 05:21:14,840
SEE A SURGEON AND HE IS THINKING

7243
05:21:14,840 --> 05:21:16,440
ABOUT JOINT REPLACEMENT, IT IS

7244
05:21:16,440 --> 05:21:18,000
NOT BECAUSE HE DOESN'T HAVE ANY

7245
05:21:18,000 --> 05:21:21,720
CARTILAGE IN HIS KNEE. IT IS

7246
05:21:21,720 --> 05:21:25,360
BECAUSE HE HAS PAIN. WE NOW KNOW

7247
05:21:25,360 --> 05:21:31,320
STEPS CLEARLY YOU DON'T TREAT

7248
05:21:31,320 --> 05:21:34,560
KNEE OA YOU TREAT THE PAIN. THEY

7249
05:21:34,560 --> 05:21:35,560
WOULD LITTLE CARTILAGE SOMETIMES

7250
05:21:35,560 --> 05:21:38,840
AND HAVE NO PAIN. SO WHAT HE

7251
05:21:38,840 --> 05:21:41,400
WHICH TRUE TO DO, IS DELAY JOINT

7252
05:21:41,400 --> 05:21:42,520
REPLACEMENT AS LATE AS POSSIBLE

7253
05:21:42,520 --> 05:21:43,880
BECAUSE WE ALL KNOW THAT IF YOU

7254
05:21:43,880 --> 05:21:45,640
GET A JOINT REPLACEMENT AT 55

7255
05:21:45,640 --> 05:21:47,840
YOU'RE GOING TO NEED ANOTHER

7256
05:21:47,840 --> 05:21:50,000
NEED OR HIP AT 75. SO FOR US WE

7257
05:21:50,000 --> 05:21:52,280
ARE TRYING TO SAY WELL, CAN WE

7258
05:21:52,280 --> 05:21:54,960
CUT THE PAIN, CAN WE DEVELOP A

7259
05:21:54,960 --> 05:21:57,240
CONSERVATIVE TREATMENT TO TRY TO

7260
05:21:57,240 --> 05:21:58,280
DEAL AS LONG AS POSSIBLE THE

7261
05:21:58,280 --> 05:22:01,520
KNEE OR THE HIP REPLACEMENT.

7262
05:22:01,520 --> 05:22:03,400
THIS IS WHAT WE HAVE DONE SO WE

7263
05:22:03,400 --> 05:22:06,080
MOW BMAC IS NOT STEM CELL

7264
05:22:06,080 --> 05:22:09,000
THERAPY, IT CONTAINS SOME STEM

7265
05:22:09,000 --> 05:22:10,720
CELLS AND CONTAIN A LOT OF

7266
05:22:10,720 --> 05:22:12,840
FACTORS SO WHAT WE DID IS

7267
05:22:12,840 --> 05:22:17,960
COMBINE DM AC TO REDUCE SCAR BUT

7268
05:22:17,960 --> 05:22:19,160
AT THE SAME TIME WE EWE

7269
05:22:19,160 --> 05:22:20,680
XENOLYTIC AGENT TO REDUCE

7270
05:22:20,680 --> 05:22:23,360
SENESCENCE SO WE REDUCE

7271
05:22:23,360 --> 05:22:25,240
INFLAMMATION IN THE CONTEXT OF

7272
05:22:25,240 --> 05:22:28,920
OA, REDUCE IT WITH SINOLITIC

7273
05:22:28,920 --> 05:22:31,240
TREATMENT, WE INJECT DMAC WITH

7274
05:22:31,240 --> 05:22:32,920
FACTORS IN IT AND AFTER THAT

7275
05:22:32,920 --> 05:22:38,160
BLOCK THE FIBROSIS. THE GOAL IS

7276
05:22:38,160 --> 05:22:40,080
TO TRY TO DELAY LONG AS POSSIBLE

7277
05:22:40,080 --> 05:22:43,360
JOINT REPLACEMENT. THAT IS

7278
05:22:43,360 --> 05:22:44,960
SOMETHING VERY IMPORTANT BECAUSE

7279
05:22:44,960 --> 05:22:47,720
PEOPLE DOESN'T COME AND SEE YOU

7280
05:22:47,720 --> 05:22:50,480
AND SAY I DON'T HAVE CARTILAGE

7281
05:22:50,480 --> 05:22:52,200
IN MY KNEE, CAN YOU PUT IT BACK

7282
05:22:52,200 --> 05:22:53,640
IN? THAT WOULD BE AWESOME BUT

7283
05:22:53,640 --> 05:22:56,320
RIGHT NOW PEOPLE ARE TRYING TO

7284
05:22:56,320 --> 05:22:57,640
DELAY THIS JOINT REPLACEMENT AS

7285
05:22:57,640 --> 05:23:06,080
LONG AS POSSIBLE.

7286
05:23:06,080 --> 05:23:13,880
>>I WOULD AGREE WITH
THAT. I'M

7287
05:23:13,880 --> 05:23:14,360
ON MUTE.

7288
05:23:14,360 --> 05:23:15,160
>>WE CAN HEAR YOU.

7289
05:23:15,160 --> 05:23:17,960
>>I HAVE HAD TWO KNEES
THAT

7290
05:23:17,960 --> 05:23:21,240
EAST LASTED 28 YEARS. THE FACT

7291
05:23:21,240 --> 05:23:24,400
THAT I'M FIVE FOOT ONE, VERY

7292
05:23:24,400 --> 05:23:29,040
PETITE, ASIAN, AS YOU MIGHT

7293
05:23:29,040 --> 05:23:31,040
THINK, AND DON'T EAT A LOT OF

7294
05:23:31,040 --> 05:23:34,840
DAIRY, NO ONE TOLD ME EARLY ON

7295
05:23:34,840 --> 05:23:37,680
EVER THAT NUTRITION THAT MY

7296
05:23:37,680 --> 05:23:39,600
JOINTS AND MY BONES NEEDED ALONG

7297
05:23:39,600 --> 05:23:44,120
THE WAY. I THINK THAT IN TODAY'S

7298
05:23:44,120 --> 05:23:45,560
HOPEFULLY FAMILY STANDARDS

7299
05:23:45,560 --> 05:23:47,000
THAT'S DIFFERENT BECAUSE WE ARE

7300
05:23:47,000 --> 05:23:49,760
VERY NUTRITIONALLY CONSCIOUS NOW

7301
05:23:49,760 --> 05:23:53,120
SO THAT CAN BE USED TO OUR, I

7302
05:23:53,120 --> 05:23:55,280
SAY OUR, THOSE WHO TRY TO KEEP

7303
05:23:55,280 --> 05:23:56,960
PEOPLE MEDICALLY STRAIGHT, IF

7304
05:23:56,960 --> 05:24:01,760
YOU WILL AND HEALTHY THAT IS ONE

7305
05:24:01,760 --> 05:24:03,440
OF MY BIG ISSUES DOING SPEECHES

7306
05:24:03,440 --> 05:24:07,360
JUST TO PATIENTS, IS EVERY

7307
05:24:07,360 --> 05:24:08,840
ASPECT THOSE KINDS OF THINGS

7308
05:24:08,840 --> 05:24:11,600
THEY CAN CONTROL, LIFESTYLE, YOU

7309
05:24:11,600 --> 05:24:12,720
EATING SLEEPING STRESS

7310
05:24:12,720 --> 05:24:13,920
MANAGEMENT, YOUR WORK LIFE YOUR

7311
05:24:13,920 --> 05:24:15,280
FAMILY LIFE YOUR CHILDREN,

7312
05:24:15,280 --> 05:24:17,600
CHILDREN'S LIVE, HOW YOU ARRANGE

7313
05:24:17,600 --> 05:24:23,000
YOUR DAY, ET CETERA, ET CETERA. 

7314
05:24:23,000 --> 05:24:25,600
IF DR. CHU WERE TO ASK ME AND

7315
05:24:25,600 --> 05:24:29,920
DR. RODEO ASK ME AMYE, WHAT ARE

7316
05:24:29,920 --> 05:24:30,520
EMERGING OPPORTUNITIES TO GO

7317
05:24:30,520 --> 05:24:33,840
INTO FROM A PATIENT PERSPECTIVE?

7318
05:24:33,840 --> 05:24:41,000
I WANT TO AVOID HAVING TO GO TO

7319
05:24:41,000 --> 05:24:44,280
DR. HUARD TO GET A JOINT

7320
05:24:44,280 --> 05:24:45,520
REPLACEMENT BUT I DON'T KNOW I

7321
05:24:45,520 --> 05:24:46,320
WAIT TOO LONG BY THE TIME THAT

7322
05:24:46,320 --> 05:24:50,560
HAPPENS.  BECAUSE WHEN PAIN

7323
05:24:50,560 --> 05:24:51,640
EMERGES IT IS SEVERE. I WOULD

7324
05:24:51,640 --> 05:24:56,360
LIKE TO KNOW EARLIER ON FROM A

7325
05:24:56,360 --> 05:24:57,360
SELF-ASSESSMENT, THIS CAN BE

7326
05:24:57,360 --> 05:24:58,560
WRAPPED AROUND JOINT YOUR

7327
05:24:58,560 --> 05:25:02,640
FINGER, WRAPPED AROUND YOUR

7328
05:25:02,640 --> 05:25:04,760
WRIST ELBOWS SHOULDERS ANKLE, I

7329
05:25:04,760 --> 05:25:07,440
HAVE HAD JOINT REPLACEMENTS IN

7330
05:25:07,440 --> 05:25:13,280
ALL THOSE THAT TELL ME YOU ARE

7331
05:25:13,280 --> 05:25:15,080
WAITING TOO MUCH ON THE LEFT

7332
05:25:15,080 --> 05:25:16,560
SIDE OF YOUR LEGS VERSUS THE

7333
05:25:16,560 --> 05:25:18,840
RIGHT SIDE YOU ARE USING YOUR

7334
05:25:18,840 --> 05:25:21,320
LEFT ARMOR THAN USING THE RIGHT

7335
05:25:21,320 --> 05:25:23,680
ARM. THERE IS BODY MECHANICS

7336
05:25:23,680 --> 05:25:25,200
ACTIVITIES THAT MAY OR MAY NOT

7337
05:25:25,200 --> 05:25:26,640
BE, HAS TO BE PROVEN FIRST, MAY

7338
05:25:26,640 --> 05:25:31,320
OR MAY NOT BE HELPFUL BUT

7339
05:25:31,320 --> 05:25:34,600
TECHNIQUES AND STRATEGIES CAN

7340
05:25:34,600 --> 05:25:36,800
HELP THE PATIENT DETERMINE HOW

7341
05:25:36,800 --> 05:25:38,120
SOON OR LATE THEY CAN COME TO

7342
05:25:38,120 --> 05:25:44,400
YOU FOR THAT KIND OF HELP. FROM

7343
05:25:44,400 --> 05:25:45,920
ORTHOPEDIC STANDPOINT I NEVER

7344
05:25:45,920 --> 05:25:47,640
ENCOUNTERED THAT. EVERY TIME I

7345
05:25:47,640 --> 05:25:49,280
DO IT IS ALWAYS YOU WAITED LONG

7346
05:25:49,280 --> 05:25:51,680
ENOUGH TO GET HER HERE. THAT WAY

7347
05:25:51,680 --> 05:25:52,960
CHOICE BECAUSE OF WHAT YOU SAID 

7348
05:25:52,960 --> 05:25:53,960
THEY DON'T LAST THAT LONG SO YOU

7349
05:25:53,960 --> 05:25:56,040
WANTED TO GET AS GREAT MILEAGE

7350
05:25:56,040 --> 05:25:57,280
AS YOU CAN. SO DELAY AS MUCH AS

7351
05:25:57,280 --> 05:26:00,960
POSSIBLE.  WHICH ARE TALKING

7352
05:26:00,960 --> 05:26:02,480
QUALITY OF LIFE, THE ABILITY FOR

7353
05:26:02,480 --> 05:26:06,920
ME TO ACCOMPLISH MY GOALS AND

7354
05:26:06,920 --> 05:26:08,400
OBJECTIVES IN LIFE. THAT IS WHAT

7355
05:26:08,400 --> 05:26:13,080
I WISH.

7356
05:26:13,080 --> 05:26:21,560
>>THANK YOU. SYSTEMS
BASED

7357
05:26:21,560 --> 05:26:23,680
APPROACH, LOOKING AT SYSTEMIC

7358
05:26:23,680 --> 05:26:29,400
FACTORS, LIFESTYLE, LOOKING AT

7359
05:26:29,400 --> 05:26:32,680
XENOLYTICS, COMBINATION THERAPY.

7360
05:26:32,680 --> 05:26:34,200
WHAT ELSE? ALONG THE LINES OF

7361
05:26:34,200 --> 05:26:36,720
NEW APPROACH?

7362
05:26:36,720 --> 05:26:39,360
>>JOHNNY, NICE COMMENTS
ABOUT

7363
05:26:39,360 --> 05:26:41,680
COMBINATION APPROACHES,

7364
05:26:41,680 --> 05:26:45,120
COMBINING XENOLYTICS OR TGF BETA

7365
05:26:45,120 --> 05:26:50,200
INHIBITION WITH OUR BIOLOGIC DU

7366
05:26:50,200 --> 05:26:51,840
JOUR. THREE HANDS RAISED, WE'LL

7367
05:26:51,840 --> 05:26:52,880
START WITH DR. BARRY.

7368
05:26:52,880 --> 05:26:55,200
>>THANKS. I WANTED TO
MENTION

7369
05:26:55,200 --> 05:26:58,920
CONTEXT OF EMERGING TECHNOLO 

7370
05:26:58,920 --> 05:27:01,080
TECHNOLOGIES, USE OF INDUCED

7371
05:27:01,080 --> 05:27:02,480
PLURIPOTENT STEM CELLS AS

7372
05:27:02,480 --> 05:27:04,040
MODALITY TO EXPLORE, MANY

7373
05:27:04,040 --> 05:27:05,880
PROBLEMS THAT WE TALKED EARLIER

7374
05:27:05,880 --> 05:27:08,360
IN TERMS OF CONSISTENCY AND

7375
05:27:08,360 --> 05:27:09,760
CHARACTERIZATION OF CELLS, MANY

7376
05:27:09,760 --> 05:27:11,160
PROBLEMS COULD POTENTIALLY GO

7377
05:27:11,160 --> 05:27:14,800
AWAY IF WE START USING INDUCE

7378
05:27:14,800 --> 05:27:17,440
PLURIPOTENT STEM CELLS AS

7379
05:27:17,440 --> 05:27:19,120
THERAPEUTIC. WE ARE EARLY DAYS

7380
05:27:19,120 --> 05:27:22,000
OF THAT YET. ALSO THE USE OF

7381
05:27:22,000 --> 05:27:25,920
IPSCs IN MODELING HASN'T

7382
05:27:25,920 --> 05:27:27,480
HAPPENED NEARLY AS MUCH IN

7383
05:27:27,480 --> 05:27:30,880
ORTHOPEDIC FEE AS IT HAS IN

7384
05:27:30,880 --> 05:27:32,880
NEUROLOGY AND THERE'S TREMENDOUS

7385
05:27:32,880 --> 05:27:33,920
OPPORTUNITIES FOR DEVELOPING NEW

7386
05:27:33,920 --> 05:27:36,880
ASSAYS AND NEW MODELS, DISEASE

7387
05:27:36,880 --> 05:27:43,120
SPECIFIC MODEL USING IPSC WE CAN

7388
05:27:43,120 --> 05:27:48,200
EXPLORE

7389
05:27:48,200 --> 05:27:51,520
>>IPS INDUCED PLURIPOTENT

7390
05:27:51,520 --> 05:27:53,640
CELLS, SCALABILITY,

7391
05:27:53,640 --> 05:27:54,640
MANUFACTURING SCALABILITY, ALL

7392
05:27:54,640 --> 05:27:56,560
THESE THINGS.

7393
05:27:56,560 --> 05:27:59,840
>>FIRST THEY PLURIPOTENT,

7394
05:27:59,840 --> 05:28:01,040
SECONDLY POTENTIALLY HAVE

7395
05:28:01,040 --> 05:28:03,560
POPULATION THAT WILL GO ON AND

7396
05:28:03,560 --> 05:28:04,880
ON AND YOU IN PRINCIPLE WON'T

7397
05:28:04,880 --> 05:28:08,120
HAVE THE PROBLEMS OF SENESCENCE

7398
05:28:08,120 --> 05:28:10,120
TRANSFORMATION OR CHROMOSOMAL

7399
05:28:10,120 --> 05:28:12,560
ABNORMALITIES YOU HAVE WITH

7400
05:28:12,560 --> 05:28:15,080
PRIMARY CELLS, THESE ARE

7401
05:28:15,080 --> 05:28:18,800
ADVANTAGES, NOT ALL FULLY

7402
05:28:18,800 --> 05:28:20,880
EXPLOITED YET BUT POTENTIAL IS

7403
05:28:20,880 --> 05:28:21,080
THERE.

7404
05:28:21,080 --> 05:28:24,720
>>NOT TO JUMP IN BUT MOST

7405
05:28:24,720 --> 05:28:27,480
SCALABLE OF CELLS, FOR REASONS

7406
05:28:27,480 --> 05:28:30,240
FRANK JUST DESCRIBED.

7407
05:28:30,240 --> 05:28:32,320
>>I AGREE WITH ALL THESE

7408
05:28:32,320 --> 05:28:34,040
COMMENTS ABOUT IPS AND LARGE

7409
05:28:34,040 --> 05:28:36,080
PART IS GETTING CONTROL OVER

7410
05:28:36,080 --> 05:28:39,640
VARIATION. THAT WE HAVE. SO IPS

7411
05:28:39,640 --> 05:28:44,200
IN CULTURE EXPANDABLE CELLS AND

7412
05:28:44,200 --> 05:28:46,800
ENGINEERS CELLS, THESE ARE

7413
05:28:46,800 --> 05:28:48,240
CLONAL CELLS FROM SINGLE GENOMIC

7414
05:28:48,240 --> 05:28:49,640
BACKGROUND, START FROM SINGLE

7415
05:28:49,640 --> 05:28:51,280
CELL, CHARACTERIZE AND MON FOR

7416
05:28:51,280 --> 05:28:53,360
OVER TIME AND THAT THEY ARE NOT

7417
05:28:53,360 --> 05:28:54,880
ALL STABLE AND THERE ARE

7418
05:28:54,880 --> 05:28:59,040
DUPLICATIONS AND MUTATIONS IPS

7419
05:28:59,040 --> 05:29:01,120
CELLS, NOT AS CLEAN UP PLATFORM

7420
05:29:01,120 --> 05:29:05,480
AS WE LOVE BUT IT WILL IMPROVE. 

7421
05:29:05,480 --> 05:29:07,240
THE COMMENT I WILL MAKE WAS

7422
05:29:07,240 --> 05:29:10,560
TWOFOLD. ONE WAS WHERE WE ARE

7423
05:29:10,560 --> 05:29:13,120
LIMITED IN A PLACE WE HAVE

7424
05:29:13,120 --> 05:29:14,000
OPPORTUNITIES IS -- I DON'T

7425
05:29:14,000 --> 05:29:17,920
THINK WE WILL MOVE FORWARD VERY

7426
05:29:17,920 --> 05:29:20,760
MUCH. WITH PRP AS A THERAPY,

7427
05:29:20,760 --> 05:29:25,800
UNTIL WE HAVE STANDARDS FOR IT. 

7428
05:29:25,800 --> 05:29:28,000
IF WE DID A STUDY WITH THIS OR

7429
05:29:28,000 --> 05:29:31,120
THAT CENTRIFUGE, I MAY OR MAY

7430
05:29:31,120 --> 05:29:34,200
NOT WORK. ONE CENTRIFUGE DOESN'T

7431
05:29:34,200 --> 05:29:37,720
WORK BUT WE DELIVERED A WIDE

7432
05:29:37,720 --> 05:29:40,080
VARIETY OF -- CENTRIFUGE BECAUSE

7433
05:29:40,080 --> 05:29:41,600
EVERY PATIENT DIFFERS.  UNTIL WE

7434
05:29:41,600 --> 05:29:44,400
HAVE A WAY TO MAKE A PRP

7435
05:29:44,400 --> 05:29:47,200
PREPARATION WHERE WE DEFINE WE

7436
05:29:47,200 --> 05:29:50,000
WANT CONCENTRATION IN THIS

7437
05:29:50,000 --> 05:29:52,200
RANGE, WE WANT TO ELIMINATE A

7438
05:29:52,200 --> 05:29:53,280
CERTAIN GROUP CYTOKINES ARE

7439
05:29:53,280 --> 05:29:55,960
WITHIN THIS RANGE, WE WANT TO

7440
05:29:55,960 --> 05:29:57,960
ELIMINATE NUCLEATED CELLS OR RED

7441
05:29:57,960 --> 05:29:59,560
CELLS WITHIN THIS RANGE SO WE

7442
05:29:59,560 --> 05:30:03,000
HAVE THAT CONTROL, THERE IS

7443
05:30:03,000 --> 05:30:05,000
HONESTLY NO WAY OR REASON FOR

7444
05:30:05,000 --> 05:30:06,440
PROSPECTIVE RANDOMIZE TRIAL, NOT

7445
05:30:06,440 --> 05:30:09,560
GOING TO MEAN ANYTHING EVEN IF

7446
05:30:09,560 --> 05:30:11,640
SUCCESSFUL OR FAIL BECAUSE ONLY

7447
05:30:11,640 --> 05:30:14,000
PROVE ONE AND ONLY ONE THING

7448
05:30:14,000 --> 05:30:15,080
THAT WE WILL WANT TO CHANGE IN

7449
05:30:15,080 --> 05:30:17,760
THE FUTURE. SO I'M NOT A GREAT

7450
05:30:17,760 --> 05:30:20,320
FAN OF INVESTING LOTS OF ENERGY

7451
05:30:20,320 --> 05:30:22,120
DESIGNING A PROSPECTIVE

7452
05:30:22,120 --> 05:30:25,320
RANDOMIZE PRP TRIAL UNLESS ALL

7453
05:30:25,320 --> 05:30:28,960
THOSE VARIABLES. THIS SPEAKS TO

7454
05:30:28,960 --> 05:30:31,840
SOMETHING AMYE BROUGHT UP, WE

7455
05:30:31,840 --> 05:30:33,200
ALSO STRUGGLE WITH PICKING THE

7456
05:30:33,200 --> 05:30:35,600
RIGHT PATIENT AND CONTROLLING

7457
05:30:35,600 --> 05:30:36,960
THE PATIENT VARIABILITY. WE HAVE

7458
05:30:36,960 --> 05:30:38,000
NO CONTROL OVER PATIENT

7459
05:30:38,000 --> 05:30:40,240
VARIABILITY. BUT ALL OUR

7460
05:30:40,240 --> 05:30:42,160
PATIENTS PRESENT WITH NOT JUST

7461
05:30:42,160 --> 05:30:43,880
ARTHRITIS IN ONE JOINT, IT COULD

7462
05:30:43,880 --> 05:30:47,680
BE MEDIAL LATERAL SIDE, FEMORAL

7463
05:30:47,680 --> 05:30:50,840
IN CASE OF KNEE AND NOT INVOLVE

7464
05:30:50,840 --> 05:30:53,120
MEDIAL LATERAL SIZE, THOSE ARE

7465
05:30:53,120 --> 05:30:53,760
DIFFERENT PROBABILITIES OF

7466
05:30:53,760 --> 05:30:56,240
FAILURE ALREADY, WE KNOW THAT

7467
05:30:56,240 --> 05:30:57,560
FEMORAL DISEASE AT LEAST IN OUR

7468
05:30:57,560 --> 05:30:59,240
PRACTICE IS A NON-RESPONDER NO

7469
05:30:59,240 --> 05:31:02,720
REASON TO OFFER SOMEBODY WITH

7470
05:31:02,720 --> 05:31:05,200
PRIMARY FEMORAL DISEASE PRP

7471
05:31:05,200 --> 05:31:06,200
INJECTION WE HAVEN'T SEEN

7472
05:31:06,200 --> 05:31:09,120
RESPONSES IN THOSE PATIENTS.  

7473
05:31:09,120 --> 05:31:11,840
BUT PATIENTS PRESENT WITH

7474
05:31:11,840 --> 05:31:13,960
OBESITY OR NOT SYSTEMIC

7475
05:31:13,960 --> 05:31:16,840
INFLAMMATORY MARKERS ARE NOT

7476
05:31:16,840 --> 05:31:19,360
OSTEOPOROSIS ARE NOT, WE ARE NOT

7477
05:31:19,360 --> 05:31:20,080
COMPARTMENTALIZING THOSE

7478
05:31:20,080 --> 05:31:22,480
PATIENTS OR CATEGORIZING OR EVEN

7479
05:31:22,480 --> 05:31:24,360
COLLECTING DATA IN A WAY

7480
05:31:24,360 --> 05:31:28,320
SYSTEMATICALLY ALLOWS US TO DO

7481
05:31:28,320 --> 05:31:30,240
RETROSPECTIVE ANALYSIS IF THERE

7482
05:31:30,240 --> 05:31:33,360
IS A COHORT OF PATIENTS WE ARE

7483
05:31:33,360 --> 05:31:37,360
PARTICULARLY GOOD OR BAD AT

7484
05:31:37,360 --> 05:31:39,240
ALREADY. OR VITAMIN D DEFICIENT

7485
05:31:39,240 --> 05:31:40,840
OR NOT, THIRD OF MY PATIENTS

7486
05:31:40,840 --> 05:31:42,640
UNDERGOING THE ARTHROPLASTY WHEN

7487
05:31:42,640 --> 05:31:46,680
WE SCREEN THEM OR VITAMIN B

7488
05:31:46,680 --> 05:31:47,960
DEFICIENT BEFORE WE COME IN AND

7489
05:31:47,960 --> 05:31:49,360
WE HAVE TO CORRECT THAT BEFORE

7490
05:31:49,360 --> 05:31:53,160
SURGERY. SO WE HAVEN'T TAKEN THE

7491
05:31:53,160 --> 05:31:54,880
SYSTEMIC APPROACH, AS ONE JOINT

7492
05:31:54,880 --> 05:31:58,080
AT A TIME APPROACH, THAT IS A

7493
05:31:58,080 --> 05:32:02,200
MISTAKE.

7494
05:32:02,200 --> 05:32:08,000
>>RIGHT ON.

7495
05:32:08,000 --> 05:32:10,960
>>GEORGE YOU HAVE THE
DATA AT

7496
05:32:10,960 --> 05:32:12,000
THE CLEVELAND CLINIC. YOU HAVE

7497
05:32:12,000 --> 05:32:14,000
BEEN DOING THIS SINCE I WAS

7498
05:32:14,000 --> 05:32:16,680
THERE. ALL THIS DATA IS RIGHT

7499
05:32:16,680 --> 05:32:20,040
THERE. YOU CAN DO THIS

7500
05:32:20,040 --> 05:32:21,680
RETROSPECTIVE ANALYSIS, YOU HAVE

7501
05:32:21,680 --> 05:32:22,760
EVERY PATIENT THERE WITH ALL

7502
05:32:22,760 --> 05:32:27,040
THAT DATA.

7503
05:32:27,040 --> 05:32:30,040
>>IT IS DESIGNED WELL,
THERE IS

7504
05:32:30,040 --> 05:32:31,800
PLACE WHERE PATIENTS ENTER DATA,

7505
05:32:31,800 --> 05:32:33,480
PLACE WHERE PHYSICIANS ENTER

7506
05:32:33,480 --> 05:32:36,520
DATA WE CAN CAPTURE THAT DATA

7507
05:32:36,520 --> 05:32:39,440
BUT HALF THE PATIENTS DON'T COME

7508
05:32:39,440 --> 05:32:42,360
BACK. WE DON'T HAVE A HIGH

7509
05:32:42,360 --> 05:32:43,360
QUALITY STUDY WE GET MORE

7510
05:32:43,360 --> 05:32:44,920
PATIENTS TO COME BACK AND

7511
05:32:44,920 --> 05:32:46,360
PROVIDE OUTCOMES SO WE CAN

7512
05:32:46,360 --> 05:32:48,920
REPORT ON PATIENTS THAT DO COME

7513
05:32:48,920 --> 05:32:50,600
BACK BUT THERE ARE PATIENTS THAT

7514
05:32:50,600 --> 05:32:52,160
DON'T COME BACK IN THE SYSTEM.

7515
05:32:52,160 --> 05:32:54,040
WE DON'T NECESSARILY

7516
05:32:54,040 --> 05:32:57,000
COMPARTMENTALIZE INFLAMMATORY

7517
05:32:57,000 --> 05:32:58,840
MARKERS OR WE HAVE MEASURES OF

7518
05:32:58,840 --> 05:33:01,640
OBESITY. WE KNOW IF THEY HAVE

7519
05:33:01,640 --> 05:33:03,600
ONE OR BOTH THESE INVOLVED BUT

7520
05:33:03,600 --> 05:33:06,480
WE DON'T HAVE NECESSARILY

7521
05:33:06,480 --> 05:33:07,720
SYSTEMATIC INFORMATION ON ALL

7522
05:33:07,720 --> 05:33:09,320
THOSE, ALL THOSE OTHER PARSING

7523
05:33:09,320 --> 05:33:10,760
PHENOMENON BUT WE ARE TRYING, I

7524
05:33:10,760 --> 05:33:14,200
THINK THAT IS THE POINT. WE DO

7525
05:33:14,200 --> 05:33:15,960
THAT DATA, I HAVE DATA CONNIE

7526
05:33:15,960 --> 05:33:17,840
HAS DATA. WE ALSO HAVE A GOOD

7527
05:33:17,840 --> 05:33:21,480
WAY TO SYSTEMATICALLY MERGE DATA

7528
05:33:21,480 --> 05:33:22,840
INTO SOMETHING WHERE WE COULD

7529
05:33:22,840 --> 05:33:27,240
MAKE IT MORE POWERFUL.

7530
05:33:27,240 --> 05:33:30,520
>>BUT THAT WOULD BE
IMPORTANT.

7531
05:33:30,520 --> 05:33:32,520
IT REALLY LOOKING AT THE

7532
05:33:32,520 --> 05:33:37,880
SYSTEMIC ASPECTS, THAT MAJOR

7533
05:33:37,880 --> 05:33:42,120
THING TO HIGHLIGHT FROM OUR

7534
05:33:42,120 --> 05:33:45,600
DISCUSSION HERE DANIEL WHITE HAS

7535
05:33:45,600 --> 05:33:46,680
HID HAND UP FOR A WHILE.

7536
05:33:46,680 --> 05:33:52,960
>>THANK YOU. ANDREAS AS
WELL.

7537
05:33:52,960 --> 05:33:56,000
>>FROM MY PERSPECTIVE AS

7538
05:33:56,000 --> 05:33:57,960
PHYSICAL THERAPIST EMERGING

7539
05:33:57,960 --> 05:33:59,200
LITERATURE ABOUT UNDERLOADING

7540
05:33:59,200 --> 05:34:03,240
BEING A RISK FACTOR FOR THE

7541
05:34:03,240 --> 05:34:05,200
DEVELOPMENT OF OSTEOARTHRITIS

7542
05:34:05,200 --> 05:34:06,360
AND PATELLA FROM OSTEOARTHRITIS

7543
05:34:06,360 --> 05:34:09,600
AND THAT HIGHLIGHTS THE NEED FOR

7544
05:34:09,600 --> 05:34:11,240
PAYING ATTENTION TO THE LOADING

7545
05:34:11,240 --> 05:34:12,320
ENVIRONMENT AND HOW IMPORTANT

7546
05:34:12,320 --> 05:34:16,280
THAT IS. ALL MAJOR MEDICAL

7547
05:34:16,280 --> 05:34:17,600
ASSOCIATIONS RECOMMEND SORT OF

7548
05:34:17,600 --> 05:34:20,560
STANDARD EXERCISE AND BEING

7549
05:34:20,560 --> 05:34:23,120
PHYSICALLY ACTIVE FOR KNEE OA. I

7550
05:34:23,120 --> 05:34:26,280
THINK AN IMPORTANT AREA TO

7551
05:34:26,280 --> 05:34:28,720
CONSIDER ARE INTERVENTIONS YOU

7552
05:34:28,720 --> 05:34:29,920
TALK ABOUT CAN BE DONE IN

7553
05:34:29,920 --> 05:34:31,920
CONJUNCTION WITH AN EXERCISE

7554
05:34:31,920 --> 05:34:33,360
PROGRAM SO THAT YOU ARE

7555
05:34:33,360 --> 05:34:36,440
LEVERAGING THE BENEFITS OF BOTH

7556
05:34:36,440 --> 05:34:41,440
EMERGING THERAPY AS WELL AS

7557
05:34:41,440 --> 05:34:45,880
TRIED AND TRUE OPTIMIZE PATIENTS

7558
05:34:45,880 --> 05:34:48,120
SORT OF HEALTH STATUS. GIVING

7559
05:34:48,120 --> 05:34:50,920
THE FAR REACHING BENEFITS OF

7560
05:34:50,920 --> 05:34:55,560
EXERCISE AND PHYSICAL ACTIVITY

7561
05:34:55,560 --> 05:34:57,920
FROM EVERYTHING FROM MOOD AND

7562
05:34:57,920 --> 05:35:01,000
PSYCHOSOCIAL STATUS TO PAIN AND

7563
05:35:01,000 --> 05:35:03,000
HEALTH RELATED QUALITY OF LIFE,

7564
05:35:03,000 --> 05:35:05,760
WHY NOT LEVERAGE THAT IN

7565
05:35:05,760 --> 05:35:08,840
ADDITION TO MERGING APPROACHES

7566
05:35:08,840 --> 05:35:15,440
AND COOL APPROACHES THAT FARSHID

7567
05:35:15,440 --> 05:35:18,160
WAS TALKING ABOUT WITH THE TRIED

7568
05:35:18,160 --> 05:35:20,920
AND TRUE. MY THOUGHTS USING A

7569
05:35:20,920 --> 05:35:23,280
MULTI-MODAL APPROACH FOR

7570
05:35:23,280 --> 05:35:23,960
INVESTIGATING USE IN THOSE

7571
05:35:23,960 --> 05:35:26,680
AREAS. 

7572
05:35:26,680 --> 05:35:29,040
>>GOOD POINTS. ANY
THOUGHTS HOW

7573
05:35:29,040 --> 05:35:36,040
THIS DATA CAN BE COLLECTED IN A

7574
05:35:36,040 --> 05:35:41,240
SYSTEMATIC AND FASHION EASY TO

7575
05:35:41,240 --> 05:35:43,520
USE?

7576
05:35:43,520 --> 05:35:47,120
>>FROM GENERAL ACTIVITY
LEVEL,

7577
05:35:47,120 --> 05:35:50,600
OBJECTIVE MONITORS USED WELL

7578
05:35:50,600 --> 05:35:52,120
ESTABLISHED TO RECORD PEOPLE'S

7579
05:35:52,120 --> 05:35:54,080
PHYSICAL ACTIVITY AS WELL AS A

7580
05:35:54,080 --> 05:35:56,360
BIG EMERGING AREA IS SEDENTARY

7581
05:35:56,360 --> 05:35:58,760
BEHAVIOR. MOST OF US ARE SITTING

7582
05:35:58,760 --> 05:35:59,920
RIGHT NOW AND HOW MUCH SITTING

7583
05:35:59,920 --> 05:36:01,200
WE ARE DOING AND HOW THAT --

7584
05:36:01,200 --> 05:36:03,440
WHAT THE RATIO OF SITTING TO

7585
05:36:03,440 --> 05:36:11,640
WALKING TO STANDING ARE. USING

7586
05:36:11,640 --> 05:36:13,280
RESEARCH GRADE MONITORS WELL

7587
05:36:13,280 --> 05:36:16,520
ESTABLISHED PROTOCOLS ARE SIMPLE

7588
05:36:16,520 --> 05:36:18,920
WAY THEY CAN BE INCORPORATED AT

7589
05:36:18,920 --> 05:36:21,120
A MINIMUM AS OUTCOME MEASURE

7590
05:36:21,120 --> 05:36:23,000
INTO ANY STUDY. HOPE THAT

7591
05:36:23,000 --> 05:36:24,320
ANSWERS YOUR QUESTION.

7592
05:36:24,320 --> 05:36:31,520
>>THANK YOU. ANDREAS. I
THINK

7593
05:36:31,520 --> 05:36:35,480
MAYBE ALSO BRIEFLY INTRODUCE

7594
05:36:35,480 --> 05:36:35,800
YOURSELF.

7595
05:36:35,800 --> 05:36:41,880
>>ANDREAS, HHS, I'M A
CLINICIAN

7596
05:36:41,880 --> 05:36:42,040
-- I

7597
05:36:42,040 --> 05:36:43,600
>>I KNOW YOU I WANTED TO
MAKE

7598
05:36:43,600 --> 05:36:46,240
SURE EVERYBODY HAD A CHANCE TO

7599
05:36:46,240 --> 05:36:46,560
HEAR YOU.

7600
05:36:46,560 --> 05:36:48,120
>>WE HAVE KNOWN EACH
OTHER FOR

7601
05:36:48,120 --> 05:36:50,080
20 YEARS. I THINK WHAT CONFUSES

7602
05:36:50,080 --> 05:36:53,200
ME AS A CLINICIAN THE MOST, THIS

7603
05:36:53,200 --> 05:36:55,280
IS PICKING UP A POINT GEORGE

7604
05:36:55,280 --> 05:37:00,320
MADE IN TERMS OF HOW IT DOESN'T

7605
05:37:00,320 --> 05:37:07,560
RESPOND TO PRP INJECTIONS. I SEE

7606
05:37:07,560 --> 05:37:11,880
PATELLA FEMORAL ISSUES AFTER A

7607
05:37:11,880 --> 05:37:15,160
ACL. TEN YEARS AGO HAD ACL BUT

7608
05:37:15,160 --> 05:37:16,680
NOW A LESION. DOESN'T MAKE SENSE

7609
05:37:16,680 --> 05:37:18,800
BUT PICKS UP ON WHAT DANIEL SAID

7610
05:37:18,800 --> 05:37:20,840
IN TERMS OF MAYBE CHANGES IN

7611
05:37:20,840 --> 05:37:23,720
QUAD STRENGTH, MAYBE PEOPLE

7612
05:37:23,720 --> 05:37:25,480
BECOME MORE HAMSTRING, THAT

7613
05:37:25,480 --> 05:37:29,880
LEADS TO ARTHRITIS.  BUT

7614
05:37:29,880 --> 05:37:31,520
ARTHRITIS IN PEOPLE WHETHER

7615
05:37:31,520 --> 05:37:32,880
PLAYED BASKETBALL SINCE THEY

7616
05:37:32,880 --> 05:37:35,760
WERE FOUR SO THAT'S REPETITIVE

7617
05:37:35,760 --> 05:37:37,320
MICROTRAUMA AND I SEE THAT IN

7618
05:37:37,320 --> 05:37:40,120
PEOPLE WITH PAT LA ALL THE TIME,

7619
05:37:40,120 --> 05:37:42,000
-- PATELLA ALL THE TIME AND

7620
05:37:42,000 --> 05:37:43,360
DON'T MECHANICALLY HAVE GOOD

7621
05:37:43,360 --> 05:37:46,880
TRACK AND THEN I SEE TIP OF

7622
05:37:46,880 --> 05:37:48,840
ICEBERG IN PATIENTS WHO HAVE

7623
05:37:48,840 --> 05:37:50,200
JOINT DISEASE. ON X-RAY THEY

7624
05:37:50,200 --> 05:37:52,240
MIGHT LOOK THE SAME AND WE ALL

7625
05:37:52,240 --> 05:37:53,840
THEM ARTHRITIS BUT THEY HAVE

7626
05:37:53,840 --> 05:37:55,880
DIFFERENT CHALLENGES AND AS LONG

7627
05:37:55,880 --> 05:37:57,520
AS WE THROW EVERYONE IN THE SAME

7628
05:37:57,520 --> 05:38:02,280
POT, SAY LET'S TREAT THIS

7629
05:38:02,280 --> 05:38:03,520
ARTHRITIS PATIENT THE RESULTS

7630
05:38:03,520 --> 05:38:05,200
AND THAT IS WHAT WE HAVE, ARE

7631
05:38:05,200 --> 05:38:10,800
VERY CONFUSING. AS CLINICIAN NOT

7632
05:38:10,800 --> 05:38:13,000
CALL PEOPLE ARTHRITIS BUT GET

7633
05:38:13,000 --> 05:38:14,160
SUBCATEGORIES AND GET BETTER, I

7634
05:38:14,160 --> 05:38:20,120
THIS I THEN OUR TRIALS WOULD BE

7635
05:38:20,120 --> 05:38:20,360
BETTER.

7636
05:38:20,360 --> 05:38:22,800
>>WE TALKED THE NEED TO

7637
05:38:22,800 --> 05:38:24,600
PHENOTYPE PATIENTS AND

7638
05:38:24,600 --> 05:38:25,680
TREMENDOUS HETEROGENEITY IN

7639
05:38:25,680 --> 05:38:27,040
PATIENT PHENOTYPE.

7640
05:38:27,040 --> 05:38:31,000
>>MULTI-DISCIPLINARY
MODELING

7641
05:38:31,000 --> 05:38:37,040
OF THE DIFFERENT OA SUB TYPES.

7642
05:38:37,040 --> 05:38:39,240
SO WE WILL DEFINITELY HIGHLIGHT

7643
05:38:39,240 --> 05:38:43,440
THOSE ARE AREAS OF -- THANK YOU,

7644
05:38:43,440 --> 05:38:45,760
ANDREAS. SHALL WE MOVE TO THE

7645
05:38:45,760 --> 05:38:48,960
NEXT TOPIC?

7646
05:38:48,960 --> 05:38:51,080
>>LARISSA'S POINT WEIGH
IN ON

7647
05:38:51,080 --> 05:38:55,040
THIS FROM THE REGULATORY.

7648
05:38:55,040 --> 05:38:57,280
>>I JUST WANTED TO COME
BACK TO

7649
05:38:57,280 --> 05:39:00,360
THE COMMENTS ABOUT THE

7650
05:39:00,360 --> 05:39:03,840
IMPORTANCE OF HAVING A STANDARD

7651
05:39:03,840 --> 05:39:07,120
DEFINING HOW YOU MAKE THESE

7652
05:39:07,120 --> 05:39:10,360
PRODUCTS WHETHER PRP CELL

7653
05:39:10,360 --> 05:39:14,880
THERAPY, STEM CELLS, MESENCHYMAL

7654
05:39:14,880 --> 05:39:16,560
STEM CELLS, MEDICINAL SIGNALING

7655
05:39:16,560 --> 05:39:18,560
CELLS, WHAT ARE ARE WE TALKING

7656
05:39:18,560 --> 05:39:21,080
ABOUT HOW ARE WE MAKING THEM,

7657
05:39:21,080 --> 05:39:23,680
THERE HAVE TO BE MORE OR LESS

7658
05:39:23,680 --> 05:39:24,920
DEFINED APPROACH. BEFORE WE GO

7659
05:39:24,920 --> 05:39:27,000
INTO CLINICAL TRIALS WE HAVE TO

7660
05:39:27,000 --> 05:39:33,240
LOOK AT THE QUALITY AND

7661
05:39:33,240 --> 05:39:34,360
CONSISTENCY HOW THESE TREATMENTS

7662
05:39:34,360 --> 05:39:39,120
ARE MADE. MAYBE AS A GROUP MAYBE

7663
05:39:39,120 --> 05:39:41,040
ONE OUTCOME OF THIS DISCUSSION

7664
05:39:41,040 --> 05:39:44,920
WE COULD FIND WAYS TO TRY TO

7665
05:39:44,920 --> 05:39:46,280
CONTRIBUTE TO DEVELOPMENT OF

7666
05:39:46,280 --> 05:39:47,120
STANDARDS HOW THESE PRODUCTS

7667
05:39:47,120 --> 05:39:49,400
COULD BE POTENTIALLY MADE BEFORE

7668
05:39:49,400 --> 05:39:54,160
THEY TRIED.  THAT IS ONE

7669
05:39:54,160 --> 05:39:55,840
COMMENT. THE OTHER IT WAS

7670
05:39:55,840 --> 05:39:59,160
STRIKING TO SEE IN THE

7671
05:39:59,160 --> 05:40:01,440
PRESENTATIONS, HOW SOMEBODY

7672
05:40:01,440 --> 05:40:03,120
LOOKED AT CLINICALTRIALS.GOV AND

7673
05:40:03,120 --> 05:40:08,080
DIFFERENT TYPES OF THERAPIES

7674
05:40:08,080 --> 05:40:09,240
WHEN THEY START WITH THOUSANDS

7675
05:40:09,240 --> 05:40:11,000
OF TRIALS AND WHEN PRODUCT GO

7676
05:40:11,000 --> 05:40:14,680
INTO PHASE 3 THERE ARE FEW LEFT.

7677
05:40:14,680 --> 05:40:16,480
I WANTED TO MAKE A POINT THERE'S

7678
05:40:16,480 --> 05:40:17,720
PROBABLY A REASON FOR WHY THERE

7679
05:40:17,720 --> 05:40:21,360
ARE FEW LEFT. BECAUSE IF THEY

7680
05:40:21,360 --> 05:40:25,800
WERE PROPERLY INVESTIGATED, THEY

7681
05:40:25,800 --> 05:40:31,560
DIDN'T WORK. SO THAT IS ANOTHER

7682
05:40:31,560 --> 05:40:33,320
CONTEXT FOR OUR BELIEFS IN

7683
05:40:33,320 --> 05:40:36,080
THINGS WE ARE TRYING TO BUY

7684
05:40:36,080 --> 05:40:39,120
OURSELVES INTO. AGAIN IT IS

7685
05:40:39,120 --> 05:40:42,040
REALLY IMPORTANT TO HAVE QUALITY

7686
05:40:42,040 --> 05:40:42,840
INVESTIGATIONS DONE WITH THESE

7687
05:40:42,840 --> 05:40:47,080
PRODUCTS AND BE A LITTLE MORE

7688
05:40:47,080 --> 05:40:50,560
SKEPTICAL BEFORE WE JUMP INTO

7689
05:40:50,560 --> 05:40:52,280
BELIEVING THINGS WILL WORK. 

7690
05:40:52,280 --> 05:40:54,120
>>I HAD TO SUMMARIZE ONE
THING

7691
05:40:54,120 --> 05:40:56,640
THAT'S COME OUT OF SIX HOURS,

7692
05:40:56,640 --> 05:40:58,680
PRIORITIES FOR MOVING FORWARD

7693
05:40:58,680 --> 05:41:03,000
CONTACTIZATION.  STANDARDIZATION

7694
05:41:03,000 --> 05:41:04,680
AND CHARACTERIZATION VARIOUS

7695
05:41:04,680 --> 05:41:07,240
WAYS GEORGE MENTIONED WITH PRP.

7696
05:41:07,240 --> 05:41:09,640
RECOGNIZE LIMITATIONS BUT

7697
05:41:09,640 --> 05:41:11,880
CLEARLY EVERYTHING STARTS THERE.

7698
05:41:11,880 --> 05:41:17,760
A ROT STARTS TH LOT OF IT STAR 

7699
05:41:17,760 --> 05:41:19,320
>>YES.

7700
05:41:19,320 --> 05:41:21,760
>>GO TO NUMBER 3,
CHALLENGES

7701
05:41:21,760 --> 05:41:30,920
AND GAPS, LOT OF THIS COME OUT. 

7702
05:41:30,920 --> 05:41:33,360
>>BACK TO AMYE, THE
QUESTION I

7703
05:41:33,360 --> 05:41:34,720
ASKED AT THE VERY BEGINNING AND

7704
05:41:34,720 --> 05:41:36,200
YOU ANSWERED NICELY, THE

7705
05:41:36,200 --> 05:41:38,440
BARRIERS TO CLINICAL TRIALS.MENT

7706
05:41:38,440 --> 05:41:42,600
SO SAY WE HAVE A PREPARATION WE

7707
05:41:42,600 --> 05:41:45,480
CAN STANDARDIZE. WE CAN

7708
05:41:45,480 --> 05:41:47,480
CHARACTERIZE IT. WE RUN A

7709
05:41:47,480 --> 05:41:49,960
CLINICAL TRIAL IN A REALISTIC

7710
05:41:49,960 --> 05:41:52,560
FASHION, HOW DO WE DO

7711
05:41:52,560 --> 05:41:55,200
MULTI-CENTRIC TRIALS. RHETORICAL

7712
05:41:55,200 --> 05:41:56,240
QUESTION CHALLENGE BUT THESE ARE

7713
05:41:56,240 --> 05:42:00,640
THE CHALLENGES. 

7714
05:42:00,640 --> 05:42:03,920
>>I HAD ADDRESS TO ONE OF
THE

7715
05:42:03,920 --> 05:42:05,520
QUESTIONS THAT WAS SUBMITTED TO

7716
05:42:05,520 --> 05:42:09,360
ME WAS HOW TO ATTRACT MORE

7717
05:42:09,360 --> 05:42:14,400
PEOPLE AND CONSISTENTLY IN

7718
05:42:14,400 --> 05:42:16,360
PEOPLE MORE THAN SEVERAL TIMES

7719
05:42:16,360 --> 05:42:19,160
WHERE PEOPLE START OUT IN

7720
05:42:19,160 --> 05:42:21,560
CLINICAL TRIALS BUT CHOOSE NOT

7721
05:42:21,560 --> 05:42:24,040
TO FURTHER PARTICIPATE. IT WAS

7722
05:42:24,040 --> 05:42:26,040
VERY CLEAR, I WAS SURPRISED THAT

7723
05:42:26,040 --> 05:42:28,880
THERE IS EVEN A CHOICE BECAUSE

7724
05:42:28,880 --> 05:42:32,680
IT WASN'T DEFINED CLEARLY ENOUGH

7725
05:42:32,680 --> 05:42:35,600
PATIENT IN TERMS OF THAT CHOICE

7726
05:42:35,600 --> 05:42:36,840
OR AT LEAST OPPORTUNITY FOR

7727
05:42:36,840 --> 05:42:39,320
FURTHER EDUCATION AND

7728
05:42:39,320 --> 05:42:42,760
EXPLANATION MAYBE SOME WIGGLE

7729
05:42:42,760 --> 05:42:45,760
ROOM, CAN'T DO TOO MUCH BUT I

7730
05:42:45,760 --> 05:42:49,360
THINK THAT PARTICULARLY IN AREA

7731
05:42:49,360 --> 05:42:51,440
OF CARTILAGE ANYTHING ABOUT

7732
05:42:51,440 --> 05:42:55,720
CARTILAGE HERE IS MY QUESTION TO

7733
05:42:55,720 --> 05:42:58,160
THE ILLUSTRIOUS PANEL FOR THOSE

7734
05:42:58,160 --> 05:43:02,680
THAT CONDUCTED STUDIES, WHAT

7735
05:43:02,680 --> 05:43:04,800
NOT, HOW DO YOU EXPLAIN IT TO A

7736
05:43:04,800 --> 05:43:09,560
PATIENT? THEY GET THE IDEA IT IS

7737
05:43:09,560 --> 05:43:12,480
CARTILAGE, I USED EDUCATIONAL

7738
05:43:12,480 --> 05:43:14,200
PATIENT LECTURERS, I USE THE

7739
05:43:14,200 --> 05:43:17,560
CHICKEN BONE AS A PERFECT

7740
05:43:17,560 --> 05:43:21,400
EXAMPLE. ARE YOU STILL DOING

7741
05:43:21,400 --> 05:43:25,240
THAT? SEEMS HIGHLY EFFECTIVE.

7742
05:43:25,240 --> 05:43:28,600
EVEN VEGANS KNOW WHAT A CHICKEN

7743
05:43:28,600 --> 05:43:30,040
BONE WITHOUT THE MEAT LOOKS

7744
05:43:30,040 --> 05:43:34,880
LIKE. AND THAT'S A GREAT START.

7745
05:43:34,880 --> 05:43:37,320
YOU HAVE TO GIVE THE PATIENT A

7746
05:43:37,320 --> 05:43:39,480
LEAP OF FAITH TO OKAY THAT IS

7747
05:43:39,480 --> 05:43:41,040
WHAT THE CARTILAGE IS, WHAT WE

7748
05:43:41,040 --> 05:43:42,920
ARE DOING OUR STUDY ON. NOW WE

7749
05:43:42,920 --> 05:43:46,160
WANT TO TEST YOURS OUT. SO THEN

7750
05:43:46,160 --> 05:43:47,880
ALL THE FEAR, ARE YOU GOING TO

7751
05:43:47,880 --> 05:43:50,200
HURT ME, PUT SOMETHING UNUSUAL

7752
05:43:50,200 --> 05:43:52,440
IN ME THAT I'M NOT GOING TO

7753
05:43:52,440 --> 05:43:54,000
CONTROL. THERE'S ALL THE

7754
05:43:54,000 --> 05:43:56,320
QUESTIONS AND IF YOU DON'T

7755
05:43:56,320 --> 05:43:57,800
ANSWER UP FRONT WILL ABSOLUTELY

7756
05:43:57,800 --> 05:43:59,200
FILTER UP, MAYBE NOT DURING

7757
05:43:59,200 --> 05:44:02,160
THEIR -- YOUR SESSION WITH THEM

7758
05:44:02,160 --> 05:44:07,480
OR YOUR NURSE PRACTITIONER

7759
05:44:07,480 --> 05:44:09,640
SESSION SESSION WITH THE PATIENT

7760
05:44:09,640 --> 05:44:12,160
BUT CERTAINLY WILL FILTER UP,

7761
05:44:12,160 --> 05:44:19,520
HAVING SOME SESSIONS IN SOME WAY

7762
05:44:19,520 --> 05:44:27,160
COLLECTIVELY SUPPORTED CONVENED

7763
05:44:27,160 --> 05:44:29,680
BY THE FDA BY LARISSA MIGHT BE

7764
05:44:29,680 --> 05:44:32,400
HELPFUL IN AREAS WHERE CLINICAL

7765
05:44:32,400 --> 05:44:33,840
TRIALS HAVE TO BE DONE ON PARTS

7766
05:44:33,840 --> 05:44:38,880
OF PEOPLE'S BODIES THAT JUST

7767
05:44:38,880 --> 05:44:42,520
SCARE THE HOLY BEJESUS OUT OF

7768
05:44:42,520 --> 05:44:44,520
THEM, THAT IS MY QUESTION TO YOU

7769
05:44:44,520 --> 05:44:47,720
HOW SUCCESSFUL HAS IT BEEN,

7770
05:44:47,720 --> 05:44:49,360
REPEAT SCENARIO WHAT IS YOUR

7771
05:44:49,360 --> 05:44:50,320
EXPERIENCE AND SHARING WHAT

7772
05:44:50,320 --> 05:44:53,560
WORKS. SHARING WHAT DOES DID NOT

7773
05:44:53,560 --> 05:44:56,920
WORK IS VALUABLE TOO.

7774
05:44:56,920 --> 05:44:58,320
>>CLINICAL TRIALS ARE
HARD

7775
05:44:58,320 --> 05:44:59,920
BECAUSE PATIENTS COME IN

7776
05:44:59,920 --> 05:45:03,400
BELIEVING THE STUFF ALL WORKS

7777
05:45:03,400 --> 05:45:05,200
AND DON'T WANT RANDOMIZE, THEY

7778
05:45:05,200 --> 05:45:06,440
WANT THE ACTIVE TREATMENT, IT IS

7779
05:45:06,440 --> 05:45:12,640
AN AREA WE AS PHYSICIANS NEED,

7780
05:45:12,640 --> 05:45:14,880
PATIENTS THINK ITAS. THAT IS ONE

7781
05:45:14,880 --> 05:45:16,880
MORE -- IT DOES. THAT IS ONE

7782
05:45:16,880 --> 05:45:18,440
MORE CHALLENGE especially

7783
05:45:18,440 --> 05:45:19,760
relevant to regenerative

7784
05:45:19,760 --> 05:45:21,320
medicine due to aggressive

7785
05:45:21,320 --> 05:45:21,920
marketing and everything out

7786
05:45:21,920 --> 05:45:24,480
there.

7787
05:45:24,480 --> 05:45:25,920
>>DANIEL, I DON'T KNOW IF
YOU

7788
05:45:25,920 --> 05:45:27,920
CAN SEE ME I HAD TO MOVE TO MY

7789
05:45:27,920 --> 05:45:34,040
CAR FROM MY OFFICE I'M SORRY. 

7790
05:45:34,040 --> 05:45:35,840
I'M QUITE COMFORTABLE ADDRESSING

7791
05:45:35,840 --> 05:45:37,000
SOME OF THOSE QUESTIONS BECAUSE

7792
05:45:37,000 --> 05:45:38,000
YOU AND OTHERS PROBABLY KNOW WE

7793
05:45:38,000 --> 05:45:39,200
HAVE DONE A COUPLE OF TRIALS

7794
05:45:39,200 --> 05:45:41,240
THAT LED TO THE REGISTRATION OF

7795
05:45:41,240 --> 05:45:42,960
THESE PROJECTS AND I EVEN HAD TO

7796
05:45:42,960 --> 05:45:45,800
TALK TO PATIENTS TO RANDOMIZE

7797
05:45:45,800 --> 05:45:47,680
AGAINST MICROFRACTURE FOR THE

7798
05:45:47,680 --> 05:45:49,040
SECOND TIME IN A SECOND

7799
05:45:49,040 --> 05:45:50,920
MULTI-CENTER TRIAL AND IT COMES

7800
05:45:50,920 --> 05:45:52,120
DOWN TO BEING HONEST AND

7801
05:45:52,120 --> 05:45:53,200
TRANSPARENT ABOUT WHAT WE KNOW

7802
05:45:53,200 --> 05:45:54,840
AND WHAT WE DON'T KNOW. AND IT

7803
05:45:54,840 --> 05:45:57,240
COMES DOWN TO THE PATIENT DOCTOR

7804
05:45:57,240 --> 05:45:59,320
TRUST AND IF THEY TRUST YOU THEY

7805
05:45:59,320 --> 05:46:00,400
WILL TRUST YOU ARE DOING THE

7806
05:46:00,400 --> 05:46:02,960
TRIAL FOR A GOOD REASON.

7807
05:46:02,960 --> 05:46:04,360
CONTRARY WHAT I HEAR PEOPLE SAY

7808
05:46:04,360 --> 05:46:05,880
I HAVE NOT FOUND A SINGLE

7809
05:46:05,880 --> 05:46:07,600
PROBLEM WITH RANDOMIZATION OF

7810
05:46:07,600 --> 05:46:10,520
THE PATIENTS. UNLESS THEY GET

7811
05:46:10,520 --> 05:46:12,920
THE IDEA THEY ARE USED FOR

7812
05:46:12,920 --> 05:46:14,600
MARKETING PURPOSES. THOSE

7813
05:46:14,600 --> 05:46:16,520
STUDIES DON'T DO WELL, BUT IF

7814
05:46:16,520 --> 05:46:20,960
THERE IS REAL SURGICAL EQUIPOISE

7815
05:46:20,960 --> 05:46:21,880
OR SCIENTIFIC UNCERTAINTY

7816
05:46:21,880 --> 05:46:23,280
PATIENT WILL FOLLOW WHAT DOCTOR

7817
05:46:23,280 --> 05:46:25,120
EXPLAINS TO THEM, IF THEY

7818
05:46:25,120 --> 05:46:26,640
EXPLAIN IT UNDERSTANDABLE TERMS 

7819
05:46:26,640 --> 05:46:36,320
THAT IS MY EXPERIENCE.

7820
05:46:36,320 --> 05:46:39,160
>>FARSH.

7821
05:46:39,160 --> 05:46:40,760
>>I HAVE A QUESTION ABOUT
THE

7822
05:46:40,760 --> 05:46:42,720
CLINICAL TRIALS ISSUE. LACK OF

7823
05:46:42,720 --> 05:46:44,000
GOOD CONTROL GROUP, THERE IS A

7824
05:46:44,000 --> 05:46:45,880
HUGE PLACEBO EFFECT IN OA

7825
05:46:45,880 --> 05:46:48,080
STUDIES PARTICULARLY IF THE KNEE

7826
05:46:48,080 --> 05:46:50,400
HAS INJECTION IN IT OR ANY

7827
05:46:50,400 --> 05:46:53,840
INJECTION OCCURS, 20 TO 40%

7828
05:46:53,840 --> 05:46:56,040
PLACEBO EFFECT. IF YOU HAVE A

7829
05:46:56,040 --> 05:46:57,480
TRIAL WITHOUT THAT IT IS NOT

7830
05:46:57,480 --> 05:47:00,520
GOING TO BE MEANINGFUL. YOU SEE

7831
05:47:00,520 --> 05:47:02,600
AN EFFECT. THE OTHER IS I HAVE

7832
05:47:02,600 --> 05:47:03,880
BEEN REVIEWING CLINICAL TRIALS

7833
05:47:03,880 --> 05:47:06,320
ON MSC AND I WOULD SAY A GOOD

7834
05:47:06,320 --> 05:47:07,880
NUMBER ARE NOT TRIALS, THEY ARE

7835
05:47:07,880 --> 05:47:10,480
JUST REGISTERED WITH NUMBER OF

7836
05:47:10,480 --> 05:47:13,560
PATIENTS FOR VARIOUS OF THESE

7837
05:47:13,560 --> 05:47:15,000
FLY BY NIGHT CLINICS TO SAY WE

7838
05:47:15,000 --> 05:47:18,320
HAVE A TRIAL ONGOING. THEREFORE

7839
05:47:18,320 --> 05:47:21,720
NEVER REPORTED. ANOTHER GROUP

7840
05:47:21,720 --> 05:47:23,680
NOT REPORTED BECAUSE THEY HAVE

7841
05:47:23,680 --> 05:47:25,480
NEGATIVE FINDINGS OR

7842
05:47:25,480 --> 05:47:26,520
INCONCLUSIVE FINDINGS, BECAUSE

7843
05:47:26,520 --> 05:47:28,760
OF THAT THERE IS INCREDIBLE

7844
05:47:28,760 --> 05:47:30,440
STATISTICAL BURDEN ON THE TRIALS

7845
05:47:30,440 --> 05:47:32,880
THAT ARE RUN PROPERLY. SO THINK

7846
05:47:32,880 --> 05:47:35,760
IF AS A LABORATORY YOU JUST

7847
05:47:35,760 --> 05:47:37,120
TOSSED 50% OF YOUR DATA BECAUSE

7848
05:47:37,120 --> 05:47:39,640
IT WASN'T SIGNIFICANT, AND YOU

7849
05:47:39,640 --> 05:47:41,000
JUST REPORTED THE POSITIVE SIDE

7850
05:47:41,000 --> 05:47:42,920
WHAT DOES THAT MEAN? TERMS OF

7851
05:47:42,920 --> 05:47:44,480
THE STATS FOR YOUR POSITIVE

7852
05:47:44,480 --> 05:47:45,520
FINDINGS? AS A FIELD WE HAVE

7853
05:47:45,520 --> 05:47:51,200
DONE THAT. SO IF WE HAVE

7854
05:47:51,200 --> 05:47:54,760
CLINICAL TRIALS NOW WE HAVE A

7855
05:47:54,760 --> 05:47:56,880
BETTER FINDING FOR IT TO BE

7856
05:47:56,880 --> 05:47:58,000
MEANINGFUL BECAUSE HALF THE

7857
05:47:58,000 --> 05:47:59,920
BATTLE IS THROWN OUT WHETHER YOU

7858
05:47:59,920 --> 05:48:01,480
THROW IT OR NOT, IT IS A BIG

7859
05:48:01,480 --> 05:48:04,560
STATISTICAL PICTURE OF WHERE WE

7860
05:48:04,560 --> 05:48:07,200
ARE AS A FIELD. BETTER OVERSIGHT

7861
05:48:07,200 --> 05:48:09,520
ON THIS AND THE REPORTING. IT IS

7862
05:48:09,520 --> 05:48:12,880
A BRAIN DUMP AND WE NEED BETTER

7863
05:48:12,880 --> 05:48:16,960
CLINICAL TRIALS, NOT JUST MORE

7864
05:48:16,960 --> 05:48:17,480
CLINICAL TRIALS.

7865
05:48:17,480 --> 05:48:21,800
>>AGREED. ALSO TO SPECIFY
AHEAD

7866
05:48:21,800 --> 05:48:26,400
OF TIME THE PRIMARY OUTCOME WE

7867
05:48:26,400 --> 05:48:28,920
TALKED THROUGH THIS MEETING

7868
05:48:28,920 --> 05:48:32,080
ABOUT HOW STRUCTURAL OUTCOMES DO

7869
05:48:32,080 --> 05:48:36,200
NOT RELATE TO PAIN OR SYMPTOMS

7870
05:48:36,200 --> 05:48:39,200
OR EVEN FUNCTION UNTIL LATE IN

7871
05:48:39,200 --> 05:48:41,520
THE DISEASE IF SOMETHING IS

7872
05:48:41,520 --> 05:48:44,760
SPECIFICALLY TO REPAIR THE

7873
05:48:44,760 --> 05:48:47,240
CARTILAGE I WOULD SUBMIT PRIMARY

7874
05:48:47,240 --> 05:48:50,640
OUTCOME SHOULD NOT BE PATIENT

7875
05:48:50,640 --> 05:48:52,640
REPORTED PAIN, THAT IS STILL AN

7876
05:48:52,640 --> 05:48:55,520
IMPORTANT OUTCOME BUT IF YOUR

7877
05:48:55,520 --> 05:48:57,120
THERAPY IS GEARED TOWARDS

7878
05:48:57,120 --> 05:48:58,800
REPAIRING AND REGENERATIVE

7879
05:48:58,800 --> 05:49:00,680
CARTILAGE, IT IS ALSO VERY

7880
05:49:00,680 --> 05:49:03,640
IMPORTANT TO HAVE A STRUCTURAL

7881
05:49:03,640 --> 05:49:06,160
OUTCOME HOW LONG IT DID THA THA.

7882
05:49:06,160 --> 05:49:07,720
NOT SAYING TO IGNORE PATIENT

7883
05:49:07,720 --> 05:49:10,560
REPORTED OUTCOME BECAUSE AS WE

7884
05:49:10,560 --> 05:49:12,320
TALKED ABOUT THAT'S THE MAIN

7885
05:49:12,320 --> 05:49:15,000
REASON THE PATIENT SEEKS

7886
05:49:15,000 --> 05:49:17,680
TREATMENT BUT SYMPTOMS MAY AS WE

7887
05:49:17,680 --> 05:49:23,160
KNOW SYMPTOMS IN OA DEVELOP

7888
05:49:23,160 --> 05:49:24,720
LATER, TYPICALLY LATER THAN

7889
05:49:24,720 --> 05:49:26,400
STRUCTURAL DISEASE SO IF WE ARE

7890
05:49:26,400 --> 05:49:29,520
TRYING TO OPT FOR EARLY

7891
05:49:29,520 --> 05:49:31,600
TREATMENT,S THE CARTILAGE REPAIR

7892
05:49:31,600 --> 05:49:35,560
PROCEDURES ARE TO ALTER

7893
05:49:35,560 --> 05:49:38,640
PRESUMABLY IMPROVE STRETCHER SO

7894
05:49:38,640 --> 05:49:39,800
THERE NEEDS TO BE MORE

7895
05:49:39,800 --> 05:49:42,240
ACCEPTANCE IN THE CLINICAL

7896
05:49:42,240 --> 05:49:44,680
TRIALS, WHAT STAGE OF OA ARE WE

7897
05:49:44,680 --> 05:49:47,360
TALKING ABOUT AND WHAT ARE THE

7898
05:49:47,360 --> 05:49:48,480
IMPORTANT OUTCOMES FOR THAT

7899
05:49:48,480 --> 05:49:53,320
STAGE. END STAGE DISEASE YES AS

7900
05:49:53,320 --> 05:49:56,120
JOHNNY AND OTHERS MENTIONED. IF

7901
05:49:56,120 --> 05:49:57,800
YOU ARE TRYING TO GET PEOPLE TO

7902
05:49:57,800 --> 05:50:01,400
HAVE LESS PAIN SO THAT THEY CAN

7903
05:50:01,400 --> 05:50:02,640
FUNCTION BETTER AND STAVE OFF

7904
05:50:02,640 --> 05:50:05,240
THE JOINT REPLACEMENT, THEN THAT

7905
05:50:05,240 --> 05:50:09,880
IS ANOTHER OUTCOME BUT EARLY ON

7906
05:50:09,880 --> 05:50:12,440
I DON'T THINK THAT CAN BE THE

7907
05:50:12,440 --> 05:50:16,440
PRIMARY OUTCOME LIKE TO ASK

7908
05:50:16,440 --> 05:50:18,200
CAROLYN LUTZKO.

7909
05:50:18,200 --> 05:50:21,360
>>YOU MAY RECALL, SO MY

7910
05:50:21,360 --> 05:50:23,280
INTEREST IS IN DEVELOPMENT AND

7911
05:50:23,280 --> 05:50:25,160
MANUFACTURING OF CELL BASED

7912
05:50:25,160 --> 05:50:26,240
THERAPIES. SO IN LISTENING

7913
05:50:26,240 --> 05:50:27,800
THROUGH THE DISCUSSION, MOST OF

7914
05:50:27,800 --> 05:50:30,880
MY WORK IS BLOOD AND GENETICS

7915
05:50:30,880 --> 05:50:35,400
RELATED. THE MOVEMENT TOWARDS

7916
05:50:35,400 --> 05:50:37,000
ALLO TRANSPLANTS OR ALLO

7917
05:50:37,000 --> 05:50:39,600
THERAPIES IS GOING TO HELP THAT

7918
05:50:39,600 --> 05:50:41,240
REALLY GETTING AT THE QUESTION

7919
05:50:41,240 --> 05:50:43,200
BECAUSE YOU CAN CENTRALIZE YOUR

7920
05:50:43,200 --> 05:50:45,440
MANUFACTURING AND IF YOU HAVE

7921
05:50:45,440 --> 05:50:49,360
MORE LIKE INVESTIGATIONAL

7922
05:50:49,360 --> 05:50:51,880
PHARMACY AT MANY SITES,

7923
05:50:51,880 --> 05:50:52,680
ENROLLMENT MAYBE DIFFERENT AT

7924
05:50:52,680 --> 05:50:54,320
LEAST YOU CAN TACKLE THAT,

7925
05:50:54,320 --> 05:50:58,520
WHETHER IT'S MSCs, EVEN PRP,

7926
05:50:58,520 --> 05:51:01,160
IT WOULD BE FROZEN,NA IPS ARE

7927
05:51:01,160 --> 05:51:04,760
GREAT WAY TO DO THAT. I THINK IT

7928
05:51:04,760 --> 05:51:07,240
COULD -- YOU CAN GET IT SOME OF

7929
05:51:07,240 --> 05:51:10,000
THESE DIFFERENTLY AS WE -- IF WE

7930
05:51:10,000 --> 05:51:13,520
CAN AND AS WE MOVE TO ALLO

7931
05:51:13,520 --> 05:51:14,440
THERAPIES.

7932
05:51:14,440 --> 05:51:17,920
>>THANK YOU.

7933
05:51:17,920 --> 05:51:23,400
>>GEORGE MUSCHLER.

7934
05:51:23,400 --> 05:51:30,120
>>I WAS GOING TO COME
BACK TO

7935
05:51:30,120 --> 05:51:31,920
COMMENT MADE IN ADDITION TO

7936
05:51:31,920 --> 05:51:34,360
BEING ABLE TO SELECT PATIENTS TO

7937
05:51:34,360 --> 05:51:35,720
BE PARTICIPANTS IN THESE STUDIES

7938
05:51:35,720 --> 05:51:38,120
GETTING THEM TO COME BACK FOR

7939
05:51:38,120 --> 05:51:40,560
FOLLOW-UP AND REMAIN YOU MADE

7940
05:51:40,560 --> 05:51:41,680
THE STATEMENT YOU CAN'T BELIEVE

7941
05:51:41,680 --> 05:51:45,840
THAT IS AN OPTION TO NOT

7942
05:51:45,840 --> 05:51:49,200
FOLLOW-UP. SO THAT IS -- WE FEEL

7943
05:51:49,200 --> 05:51:50,760
THAT WAY TOO BUT THE ONLY POWER

7944
05:51:50,760 --> 05:51:53,200
THAT CLINICIANS HAVE IS TO BUILD

7945
05:51:53,200 --> 05:51:56,720
TRUST AS SHANE MENTIONED AND

7946
05:51:56,720 --> 05:51:59,200
DANIEL MENTIONED AND TO SHOW THE

7947
05:51:59,200 --> 05:52:00,200
PATIENT YOU CARE ABOUT THEM

7948
05:52:00,200 --> 05:52:04,000
COMING BACK. CLINICAL

7949
05:52:04,000 --> 05:52:05,760
COORDINATORS ARE ESSENTIAL IN

7950
05:52:05,760 --> 05:52:09,600
THAT PROCESS. TO THIS DAY BUT

7951
05:52:09,600 --> 05:52:14,280
STILL PATIENTS HAVE OPTIONS. AND

7952
05:52:14,280 --> 05:52:17,920
ONE OF THE LEVERS THAT HAS NOT

7953
05:52:17,920 --> 05:52:19,440
BEEN APPLIED TO THESE STUDIES

7954
05:52:19,440 --> 05:52:21,360
AND THERE MAYBE AN OPPORTUNITY

7955
05:52:21,360 --> 05:52:26,120
TO DO THAT IS TO PARTNER WITH

7956
05:52:26,120 --> 05:52:27,880
PAYERS BECAUSE YOU CAN IMAGINE A

7957
05:52:27,880 --> 05:52:29,200
PATIENT WHO WOULD LIKE TO HAVE

7958
05:52:29,200 --> 05:52:31,920
ACCESS TO THESE THERAPIES AND

7959
05:52:31,920 --> 05:52:33,800
LIKE TO BE PARTICIPANT IN A

7960
05:52:33,800 --> 05:52:37,680
STUDY, A PAYER WHO WOULD LIKE

7961
05:52:37,680 --> 05:52:41,760
KNEE REPLACEMENTS AND HAVE

7962
05:52:41,760 --> 05:52:42,600
CHEAPER OPTION BUT WOULD

7963
05:52:42,600 --> 05:52:43,760
REIMBURSE A PATIENT ONLY IF THEY

7964
05:52:43,760 --> 05:52:47,160
CAME BACK TO FOLLOW-UP. AS PART

7965
05:52:47,160 --> 05:52:48,520
OF THE STUDY. THERE IS AN

7966
05:52:48,520 --> 05:52:50,320
OPPORTUNITY THERE. WE GOT A

7967
05:52:50,320 --> 05:52:53,920
LITTLE WAY DOWN THE ROAD WITH

7968
05:52:53,920 --> 05:52:55,280
MEDICAL ABOUT SIX OR EIGHT YEARS

7969
05:52:55,280 --> 05:53:00,160
AGO AND SOME LEADERSHIP CHANGED 

7970
05:53:00,160 --> 05:53:03,320
BUT THERE IS AN OPTION WHERE FOR

7971
05:53:03,320 --> 05:53:05,520
ANY OF US WHO LIVE IN AN

7972
05:53:05,520 --> 05:53:07,880
ENVIRONMENT WITH COLLABORATIVE

7973
05:53:07,880 --> 05:53:12,080
PAYER TO IMPROVE PATIENT

7974
05:53:12,080 --> 05:53:15,160
PARTICIPATION.

7975
05:53:15,160 --> 05:53:19,160
>>THANK YOU. I THINK
DAN'S

7976
05:53:19,160 --> 05:53:20,960
COMMENT HIGHLIGHTED THE

7977
05:53:20,960 --> 05:53:24,240
IMPORTANCE OF BUILDING TRUST IN

7978
05:53:24,240 --> 05:53:27,120
TRANSPARENCY AND IF YOU HAVE THE

7979
05:53:27,120 --> 05:53:29,240
PAYERS INVOLVED ARE YOU

7980
05:53:29,240 --> 05:53:33,280
CONCERNED GEORGE, THERE MAYBE

7981
05:53:33,280 --> 05:53:36,000
EFFECT ON HOW PATIENT VIEWS

7982
05:53:36,000 --> 05:53:37,680
THEIR TREATMENT?

7983
05:53:37,680 --> 05:53:39,600
>>HOPEFULLY NOT,
HOPEFULLY THEY

7984
05:53:39,600 --> 05:53:44,480
-- IN OUR CASE WHERE OUR OPINION

7985
05:53:44,480 --> 05:53:47,040
IS THAT WE USE SIX MONTH

7986
05:53:47,040 --> 05:53:48,960
FOLLOW-UP AS WINDOW SO NOT A

7987
05:53:48,960 --> 05:53:50,360
LONG FOLLOW UP, WE KNOW IT IS

7988
05:53:50,360 --> 05:53:51,920
WITHIN A YEAR PATIENTS ARE

7989
05:53:51,920 --> 05:53:53,240
THINKING OF US, THEY HAVEN'T

7990
05:53:53,240 --> 05:53:54,160
CHANGED THEIR ADDRESS OR PHONE

7991
05:53:54,160 --> 05:54:00,200
NUMBER. NOT CHANGED JOBS SO IT

7992
05:54:00,200 --> 05:54:02,440
IS POSSIBLE TO REACH THEM. THEY

7993
05:54:02,440 --> 05:54:04,080
STILL HAVE THE SAME PAYER DURING

7994
05:54:04,080 --> 05:54:07,040
THAT TIME. THERE IS NO REASON TO

7995
05:54:07,040 --> 05:54:08,920
MAKE THIS CO-WE ARESIVE, WE WANT

7996
05:54:08,920 --> 05:54:11,880
TO KNOW, ARE YOU BETTER, WORSE,

7997
05:54:11,880 --> 05:54:13,840
DO YOU CLIMB STAIRS, NOT CLIMB

7998
05:54:13,840 --> 05:54:15,840
STAIRS B ARE YOU STILL WORKING,

7999
05:54:15,840 --> 05:54:17,280
STILL PLAY SPORTS, THERE IS A

8000
05:54:17,280 --> 05:54:18,280
LIMITED NUMBER OF QUESTIONS AND

8001
05:54:18,280 --> 05:54:19,720
WE DON'T HAVE TO DESIGN IT IN A

8002
05:54:19,720 --> 05:54:22,040
WAY TO PHYSICALLY COME BACK

8003
05:54:22,040 --> 05:54:26,120
UNLESS WE HAVE IMAGING TO DO OR

8004
05:54:26,120 --> 05:54:27,440
INFLAMMATORY MARKERS TO DO OTHER

8005
05:54:27,440 --> 05:54:29,440
THINGS BUT WE CAN MAKE IT EASY

8006
05:54:29,440 --> 05:54:32,000
ENOUGH TO PATIENTS TO DO IT. I

8007
05:54:32,000 --> 05:54:33,200
THINK IT IS -- THERE IS NO

8008
05:54:33,200 --> 05:54:36,160
REASON WE SHOULDN'T HAVE 80 TO

8009
05:54:36,160 --> 05:54:37,400
90% FOLLOW-UP ON THESE STUDIES

8010
05:54:37,400 --> 05:54:40,040
IF WE CAN ALIGN PROCESS AND MAKE

8011
05:54:40,040 --> 05:54:42,200
EASY FOR PATIENTS TO COMMUNICATE

8012
05:54:42,200 --> 05:54:44,160
WELL BUT ALSO MOTIVATE THEM SO

8013
05:54:44,160 --> 05:54:46,800
THEY ARE NOT INCLINED IF THEY

8014
05:54:46,800 --> 05:54:50,080
ARE UNCERTAIN ABOUT OUTCOME OR

8015
05:54:50,080 --> 05:54:50,720
ANOTHER SHINEC OBJECT SHOWS UP

8016
05:54:50,720 --> 05:54:53,560
ON COMPUTER SCREEN AND THEY WANT

8017
05:54:53,560 --> 05:54:55,840
WANT THE TRY SOMETHING ELSE,

8018
05:54:55,840 --> 05:54:58,400
THEY FEEL GUILTY BECAUSE THEY

8019
05:54:58,400 --> 05:55:00,040
DID SOMETHING ELSE, WE DON'T

8020
05:55:00,040 --> 05:55:05,320
WANT THEM TO FEEL GUILTY ABOUT

8021
05:55:05,320 --> 05:55:08,920
THAT. THERE IS HOPE IN

8022
05:55:08,920 --> 05:55:10,920
COMMUNICATING BUT I DON'T

8023
05:55:10,920 --> 05:55:13,360
PRETEND IT IS EASY BUT ONE EXTRA

8024
05:55:13,360 --> 05:55:16,280
LEVER. I DON'T THINK IT WOULD

8025
05:55:16,280 --> 05:55:19,080
COME, WE ARE NOT ASKING THEM --

8026
05:55:19,080 --> 05:55:21,960
NOT PUTTING THEM AT RISK.

8027
05:55:21,960 --> 05:55:24,880
>>WE COULD ALWAYS
CONSIDER

8028
05:55:24,880 --> 05:55:30,480
PCORI WAY WHICH IS PCORI

8029
05:55:30,480 --> 05:55:33,760
BASICALLY SAYS YOU WILL PAY

8030
05:55:33,760 --> 05:55:35,200
PATIENTS FOR THEIR

8031
05:55:35,200 --> 05:55:36,400
PARTICIPATION, YOU WILL PAY

8032
05:55:36,400 --> 05:55:40,400
PATIENTS WHO ARE SITTING ON YOUR

8033
05:55:40,400 --> 05:55:41,280
INVESTIGATION COMMITTEE. YOU

8034
05:55:41,280 --> 05:55:43,200
WILL PAY THE PATIENT OR TWO

8035
05:55:43,200 --> 05:55:46,160
SITTING ON EXECUTIVE PROJECT

8036
05:55:46,160 --> 05:55:48,560
COMMITTEE. THE PAYMENT IS VERY

8037
05:55:48,560 --> 05:55:51,720
-- IT IS UNDER $50. L IN SOME

8038
05:55:51,720 --> 05:55:54,920
CASES WE HAVE SEEN WHERE

8039
05:55:54,920 --> 05:55:57,560
PROBABLY OUT OF $50 PER PERSON

8040
05:55:57,560 --> 05:56:01,200
MAX OVER THE TIME -- NUMBERS OF

8041
05:56:01,200 --> 05:56:03,200
RESPONSES THAT THEY WILL NEED TO

8042
05:56:03,200 --> 05:56:06,040
GIVE, THEY WILL GIVE THEM A

8043
05:56:06,040 --> 05:56:07,920
LITTLE BIT MORE UP FRONT AND

8044
05:56:07,920 --> 05:56:11,120
FOLLOW-UP WITH A BIG HIT AT THE

8045
05:56:11,120 --> 05:56:15,160
END IF YOU WILL. YOU ARE TALKING

8046
05:56:15,160 --> 05:56:15,520
$35.

8047
05:56:15,520 --> 05:56:18,080
>>THIS IS DANIEL SORRY TO

8048
05:56:18,080 --> 05:56:22,720
INTERRUPT BUT I THINK THAT THE

8049
05:56:22,720 --> 05:56:24,760
ROLE OF THE CRC, STUDY

8050
05:56:24,760 --> 05:56:26,680
COORDINATOR OR DESK ATTENDANT

8051
05:56:26,680 --> 05:56:29,120
FIRST POINT OF CONTACT IS

8052
05:56:29,120 --> 05:56:29,920
IMPERATIVE.  ALSO THE FIRST

8053
05:56:29,920 --> 05:56:31,360
DISCUSSION THAT WE HAVE HAD WITH

8054
05:56:31,360 --> 05:56:34,440
PATIENTS IN ALL THESE TRIALS IS

8055
05:56:34,440 --> 05:56:36,440
IS -- WE DON'T HAVE GOOD DATA WE

8056
05:56:36,440 --> 05:56:38,280
REALLY DON'T HAVE GOOD TRIALS,

8057
05:56:38,280 --> 05:56:40,520
THIS COULD BE A GOOD TRIAL BUT

8058
05:56:40,520 --> 05:56:42,280
WE NEED EVERYBODY TO PARTICIPATE

8059
05:56:42,280 --> 05:56:44,200
IN THE WHOLE TRAJECTORY SO THEY

8060
05:56:44,200 --> 05:56:45,840
ARE NOT JUST A SUBJECT, THEY ARE

8061
05:56:45,840 --> 05:56:47,520
A TEAM MEMBER. THE MOMENT THE

8062
05:56:47,520 --> 05:56:48,640
PATIENT UNDERSTANDS THEY ARE

8063
05:56:48,640 --> 05:56:50,400
PART OF THE TEAM DOING THE TRIAL

8064
05:56:50,400 --> 05:56:52,680
NOT JUST PART OF THE SUBJECTS

8065
05:56:52,680 --> 05:56:54,760
STUDIED, THE ENGAGEMENT IS MUCH

8066
05:56:54,760 --> 05:56:56,320
DIFFERENT. WE EVEN HAD PEOPLE

8067
05:56:56,320 --> 05:56:58,320
ASK TO CONTINUE TO FIVE AND TEN

8068
05:56:58,320 --> 05:57:02,720
YEARS AND HAVE A SURGICAL

8069
05:57:02,720 --> 05:57:04,320
ARTHROSCOPY, THESE ARE NOT CRAZY

8070
05:57:04,320 --> 05:57:05,720
PEOPLE, PEOPLE TRYING TO

8071
05:57:05,720 --> 05:57:08,400
CONTRIBUTE. THAT IS WHY U YOU

8072
05:57:08,400 --> 05:57:10,600
HAVE 98 AND 100% FOLLOW-UP IF

8073
05:57:10,600 --> 05:57:12,320
PATIENTS ARE ENGAGED IN RESEARCH

8074
05:57:12,320 --> 05:57:15,000
QUESTION, THEY ALSO IF THEY DROP

8075
05:57:15,000 --> 05:57:16,560
OUT IF THEY DON'T SEND IN THEIR

8076
05:57:16,560 --> 05:57:17,560
QUESTIONNAIRES ANY MORE, THE

8077
05:57:17,560 --> 05:57:19,960
STUDY WILL BE AT RISK AND SHARE

8078
05:57:19,960 --> 05:57:21,000
RESPONSIBILITY AND THAT IS ONE

8079
05:57:21,000 --> 05:57:22,640
ASPECT. AND THE OTHER ASPECT

8080
05:57:22,640 --> 05:57:26,360
THAT IS BENEFICIAL NOW IS THAT

8081
05:57:26,360 --> 05:57:27,000
THROUGH TELEHEALTH OPPORTUNITIES

8082
05:57:27,000 --> 05:57:29,280
HAVE EXPANDED THROUGH COVID

8083
05:57:29,280 --> 05:57:30,640
REGULATION, WE ARE ABLE TO DO

8084
05:57:30,640 --> 05:57:32,640
MORE FOLLOW-UPS THROUGH VIRTUAL

8085
05:57:32,640 --> 05:57:35,360
CONSULTATION AND NOT EVERY TIME

8086
05:57:35,360 --> 05:57:37,000
DO I NEED TO TOUCH THE PATIENT

8087
05:57:37,000 --> 05:57:38,760
MYSELF OR DO A KNEE EXAM MYSELF,

8088
05:57:38,760 --> 05:57:40,840
IF THE IMAGING PROTOCOL IS WELL

8089
05:57:40,840 --> 05:57:41,840
ESTABLISHED THEY CAN HAVE

8090
05:57:41,840 --> 05:57:44,160
IMAGING PROTOCOLS DONE LOCALLY

8091
05:57:44,160 --> 05:57:46,160
IN SCANNERS VALIDATED WITHIN THE

8092
05:57:46,160 --> 05:57:48,400
TRIAL. AND YOU CAN DO FOLLOW-UP

8093
05:57:48,400 --> 05:57:49,280
THROUGH QUESTIONNAIRES AND

8094
05:57:49,280 --> 05:57:51,520
VIRTUAL CONSULTATION WHICH

8095
05:57:51,520 --> 05:57:53,000
LIMITS THE TRAVEL RISK AND THE

8096
05:57:53,000 --> 05:57:55,840
DROP OUT SO EVOLVING

8097
05:57:55,840 --> 05:57:57,080
TECHNOLOGIES ARE TO OUR BENEFIT

8098
05:57:57,080 --> 05:57:59,600
I THINK. HIGH QUALITY FOLLOW-UP

8099
05:57:59,600 --> 05:58:02,080
IS IMPERATIVE FOR THE TRIAL. IF

8100
05:58:02,080 --> 05:58:04,480
YOU DROP BELOW 90% THE CHILD IS

8101
05:58:04,480 --> 05:58:05,640
AT RISK. 

8102
05:58:05,640 --> 05:58:12,760
>>THANK YOU. SO WE ARE
NOW AT

8103
05:58:12,760 --> 05:58:17,040
5:20. SO WE ARE SCHEDULED TO

8104
05:58:17,040 --> 05:58:22,440
HEAR FROM LINDSEY AND BOB

8105
05:58:22,440 --> 05:58:22,680
CARTER.

8106
05:58:22,680 --> 05:58:26,960
>>YES, THANK YOU. SO
MUCH. I

8107
05:58:26,960 --> 05:58:29,160
WILL ASK BOB TO OFFER COMMENTS

8108
05:58:29,160 --> 05:58:30,480
FIRST THEN FOLLOW AFTER THAT.

8109
05:58:30,480 --> 05:58:31,760
>>THANK YOU.

8110
05:58:31,760 --> 05:58:33,640
>>THIS HAS BEEN A
FANTASTIC

8111
05:58:33,640 --> 05:58:36,120
MEETING. REALLY APPRECIATE

8112
05:58:36,120 --> 05:58:39,760
THOUGHTFUL INPUTS FROM AND THE

8113
05:58:39,760 --> 05:58:42,640
TALKS WAROR WERE SUPERB. SO

8114
05:58:42,640 --> 05:58:44,280
THANKFUL FOR YOUR TIME AND

8115
05:58:44,280 --> 05:58:46,480
EFFORT. I DO THINK REGENERATIVE

8116
05:58:46,480 --> 05:58:50,360
MEDICINE IS FUTURE. I DO THINK

8117
05:58:50,360 --> 05:58:51,600
WE SOME DAY YOU CAN IMAGINE WE

8118
05:58:51,600 --> 05:58:53,040
WILL HAVE A THERAPY OR

8119
05:58:53,040 --> 05:58:54,480
COMBINATION OF THERAPIES THAT IN

8120
05:58:54,480 --> 05:58:58,240
SOME PEOPLE ARE GOING TO LEAD TO

8121
05:58:58,240 --> 05:59:00,720
HEALING OF CARTILAGE AND

8122
05:59:00,720 --> 05:59:02,840
ABEYANCE OF OTHER FACTORS THAT

8123
05:59:02,840 --> 05:59:07,440
LEAD TO REPETSIVE DEGENERATION

8124
05:59:07,440 --> 05:59:09,200
INFLAMMATORY CHANGES. SO WE ARE

8125
05:59:09,200 --> 05:59:13,080
AT THE VERY EARLY STAGE OF THIS.

8126
05:59:13,080 --> 05:59:16,840
WE ARE WORKING THROUGH THE

8127
05:59:16,840 --> 05:59:17,840
LOOKING GLASS TRYING TO FIGURE

8128
05:59:17,840 --> 05:59:18,960
HOW TO GET ON THE OTHER SIDE OF

8129
05:59:18,960 --> 05:59:25,000
IT. SO I DO THINK WE NEED A WIN 

8130
05:59:25,000 --> 05:59:26,480
I THINK ALL THIS STUFF GOING ON

8131
05:59:26,480 --> 05:59:28,800
IN SOCIETY, FOCUS ON WHAT IS IT

8132
05:59:28,800 --> 05:59:30,680
GOING TO TAKE TO HAVE A

8133
05:59:30,680 --> 05:59:33,400
DEMONSTRATION THAT WE CAN

8134
05:59:33,400 --> 05:59:35,560
IMPROVE THINGS? WE ACTUALLY HAVE

8135
05:59:35,560 --> 05:59:37,320
GOOD DATA WE CAN REGROW

8136
05:59:37,320 --> 05:59:40,920
CARTILAGE WITH FGF 18, IT DID

8137
05:59:40,920 --> 05:59:42,360
REGROW IT ON LATERAL SIDE,

8138
05:59:42,360 --> 05:59:44,120
DIDN'T REDUCE PAIN SO PROGRAM

8139
05:59:44,120 --> 05:59:47,600
WAS STOPPED. WE DO KNOW FROM

8140
05:59:47,600 --> 05:59:49,560
THAT AND THE DISTRACTION STUDIES

8141
05:59:49,560 --> 05:59:52,000
THAT WE CAN LEAD TO REGROWTH OF

8142
05:59:52,000 --> 05:59:53,920
CARTILAGE IN PATIENTS WITH

8143
05:59:53,920 --> 06:00:00,480
ACTIVE OA IN HUMANS. HUMANS. SOE

8144
06:00:00,480 --> 06:00:02,240
STARTING POINTS REASONABLE TO

8145
06:00:02,240 --> 06:00:03,240
BELIEF WILL WORK BUT WE HAVE TO

8146
06:00:03,240 --> 06:00:04,800
GET A WIN TO SAY HERE IS A PLACE

8147
06:00:04,800 --> 06:00:07,640
WHERE IT WORKS. TO GEORGE'S

8148
06:00:07,640 --> 06:00:09,320
POINT, NOT ONLY HAVE TO BE

8149
06:00:09,320 --> 06:00:12,120
DEFINED IN TERMS OF

8150
06:00:12,120 --> 06:00:13,560
INTERVENTION, ALSO DEFINED ON

8151
06:00:13,560 --> 06:00:16,080
WHO THE SUBJECTS ARE.

8152
06:00:16,080 --> 06:00:18,840
PARTICIPANTS. PARTNERS IN THE

8153
06:00:18,840 --> 06:00:22,320
STUDY. DEFINING THE PEOPLE YOU

8154
06:00:22,320 --> 06:00:23,920
THINK MOST LIKELY TO RESPOND

8155
06:00:23,920 --> 06:00:27,840
DEFINING THE THERAPY IN TERMS OF

8156
06:00:27,840 --> 06:00:30,560
ALL THINGS YOU SAID IN TERMS OF

8157
06:00:30,560 --> 06:00:31,720
HOW TO CHARACTERIZE IT AND

8158
06:00:31,720 --> 06:00:33,760
FINDING A WAY TO GET A WIN, THIS

8159
06:00:33,760 --> 06:00:35,560
ACTUALLY WORKS WHETHER PRP OR

8160
06:00:35,560 --> 06:00:40,600
EXOSOMES OR CELLS.  I DID GO

8161
06:00:40,600 --> 06:00:43,600
BACK ORS TALK TALK ABOUT THEIR

8162
06:00:43,600 --> 06:00:45,280
VERSION OF THE MEAN, DEGREE OF

8163
06:00:45,280 --> 06:00:47,040
REVERSION TO MEAN IN PATIENTS

8164
06:00:47,040 --> 06:00:49,680
WITH PAIN IS ASTOUNDING. IF THE

8165
06:00:49,680 --> 06:00:51,880
STUDIES ARE NOT WELL CONTROLLED,

8166
06:00:51,880 --> 06:00:53,680
THE REVERSION OF THE MEAN NOT TO

8167
06:00:53,680 --> 06:00:56,000
MENTION PLACEBO EFFECT, THE

8168
06:00:56,000 --> 06:00:58,400
VERSION OF THE MEAN IS OFTEN

8169
06:00:58,400 --> 06:01:00,320
MUCH GREATER. WE WHERE OVERWHELM

8170
06:01:00,320 --> 06:01:02,080
ANY SIGNALING WE HAVE SO WE HAVE

8171
06:01:02,080 --> 06:01:06,640
DEAL WITH THAT. ONCE WE HAVE THE

8172
06:01:06,640 --> 06:01:08,320
BIN WELCOME CHARACTERIZE

8173
06:01:08,320 --> 06:01:10,360
JOHNNY'S PART OF THIS, HIS CELLS

8174
06:01:10,360 --> 06:01:13,200
ARE SENT TO CENTER WHERE THEY

8175
06:01:13,200 --> 06:01:15,600
WILL DO IN DEPTH CELL CHARACTER

8176
06:01:15,600 --> 06:01:17,240
CAUTIONS AS PART OF REGENERATIVE

8177
06:01:17,240 --> 06:01:20,840
MEDICINE INNOVATION PROJECT, WE

8178
06:01:20,840 --> 06:01:24,280
DO NEED TO UNDERSTAND WHAT IS

8179
06:01:24,280 --> 06:01:26,040
GOING ON, I THINK TO THE POINT

8180
06:01:26,040 --> 06:01:27,800
DR. BARRY MADE ABOUT CURRENT

8181
06:01:27,800 --> 06:01:31,480
STANDARDS ARE NOT SUFFICIENT.

8182
06:01:31,480 --> 06:01:33,920
ONCE WE HAVE A WIN WE CAN START

8183
06:01:33,920 --> 06:01:35,560
INVESTIGATING MECHANISMS IN

8184
06:01:35,560 --> 06:01:37,640
HUMAN AND BROADENING OUT -- THIS

8185
06:01:37,640 --> 06:01:40,280
IS THE POPULATION WE SEE -- WE

8186
06:01:40,280 --> 06:01:44,000
CAN BELIEVE. WHAT IS MORE

8187
06:01:44,000 --> 06:01:46,920
GENERAL YOU KNOW THIS IS A WIN,

8188
06:01:46,920 --> 06:01:48,360
PEOPLE WANT TO BE REIMBURSED BUT

8189
06:01:48,360 --> 06:01:50,080
AS SCIENTIST, OUR JOB IS TO

8190
06:01:50,080 --> 06:01:53,960
FIGURE OUT WHO RESPONDS TO WHICH

8191
06:01:53,960 --> 06:01:55,200
PREPARATIONS. I DON'T KNOW NIAMS

8192
06:01:55,200 --> 06:01:57,760
CAN FUND THE TRIAL WE NEED.  IT

8193
06:01:57,760 --> 06:01:59,160
MAY LEAD TO BIG IN THE CELL

8194
06:01:59,160 --> 06:02:01,760
PREPS IF THAT IS WHERE WE GOING,

8195
06:02:01,760 --> 06:02:03,480
MAYBE TOO EXPENSIVE FOR US. WE

8196
06:02:03,480 --> 06:02:06,600
HAVE TO FIGURE HOW TO GET THAT

8197
06:02:06,600 --> 06:02:09,400
DONE AND IT MAY NOT BE ONE AND

8198
06:02:09,400 --> 06:02:13,960
DONE.  THIS IS EXPENSIVE PATH.

8199
06:02:13,960 --> 06:02:15,200
WITH THAT, I THINK THERE IS

8200
06:02:15,200 --> 06:02:21,000
HONEHOPE. WE WILL GET THERE, MAE

8201
06:02:21,000 --> 06:02:23,520
TAKE FIVE YEARS, 50, A HUNDRED

8202
06:02:23,520 --> 06:02:25,080
BUT THIS IS THE FUTURE, WE ARE

8203
06:02:25,080 --> 06:02:26,200
JUST STARTING COULDN'T THE PATH,

8204
06:02:26,200 --> 06:02:28,000
WE ARE EXPLORE -- DOWN THE PATH.

8205
06:02:28,000 --> 06:02:30,640
WE WANT TO FIGURE HOW TO MAKE

8206
06:02:30,640 --> 06:02:31,920
THAT PATH STRAIGHT AS POSSIBLE.

8207
06:02:31,920 --> 06:02:33,120
THANK YOU FOR THE PARTICIPATION.

8208
06:02:33,120 --> 06:02:34,560
HAVING SAID THAT, I DON'T HAVE

8209
06:02:34,560 --> 06:02:37,400
TO PAY FOR IT, I'M GOING TO TURN

8210
06:02:37,400 --> 06:02:38,080
IT OVER TO LINDSEY.

8211
06:02:38,080 --> 06:02:40,400
>>SKIP THAT QUESTION
NUMBER 4

8212
06:02:40,400 --> 06:02:41,800
WHAT DO WE NEED BESIDES MONEY,

8213
06:02:41,800 --> 06:02:43,040
RIGHT?

8214
06:02:43,040 --> 06:02:48,600
>>YEAH. NO. BOY, AM I
GRATEFUL

8215
06:02:48,600 --> 06:02:50,000
TO THE EFFORT DEVOTED TO

8216
06:02:50,000 --> 06:02:51,800
ORGANIZING THIS AND TO ALL OF

8217
06:02:51,800 --> 06:02:53,480
YOU WHO SPENT SO MANY HOURS WITH

8218
06:02:53,480 --> 06:02:57,480
US, IT WAS A FASCINATING

8219
06:02:57,480 --> 06:03:00,200
DISCUSSION, I LEARNED A

8220
06:03:00,200 --> 06:03:02,760
TREMENDOUS AMOUNT, I WAS WRITING

8221
06:03:02,760 --> 06:03:04,720
DOWN HIGH LEVEL THEMES AS WE

8222
06:03:04,720 --> 06:03:05,520
REMEMBER GOING ALONG, BOB

8223
06:03:05,520 --> 06:03:08,000
TOUCHED UPON SO MANY OF THEM,

8224
06:03:08,000 --> 06:03:09,320
JUST CRITICAL IMPORTANCE OF

8225
06:03:09,320 --> 06:03:10,880
STUDY DESIGN, CHARACTERIZATION

8226
06:03:10,880 --> 06:03:12,400
AND STANDARDIZATION OF THE

8227
06:03:12,400 --> 06:03:15,600
PRODUCT, AND PROCESSES. T THE

8228
06:03:15,600 --> 06:03:17,600
HETEROGENEITY OF THE PATIENTS

8229
06:03:17,600 --> 06:03:20,600
FROM MINOR STRUCTURAL DEFECTS TO

8230
06:03:20,600 --> 06:03:21,360
GENERALIZED OSTEOARTHRITIS OF

8231
06:03:21,360 --> 06:03:23,880
DECADES AND DURATION AND THE

8232
06:03:23,880 --> 06:03:24,440
IMPORTANCE OF BETTER

8233
06:03:24,440 --> 06:03:26,920
UNDERSTANDING THE MECHANISMS. I

8234
06:03:26,920 --> 06:03:30,120
LOVED WHO WAS IT THAT SAID I'M

8235
06:03:30,120 --> 06:03:31,360
FORGETTING OFF THE TOP OF MY

8236
06:03:31,360 --> 06:03:35,120
HEAD, ONE OF OUR PARTICIPANTS

8237
06:03:35,120 --> 06:03:37,760
PERHAPS A GOAL TREESIS ON MOVING

8238
06:03:37,760 --> 06:03:40,200
FORWARD, BOY THAT WOULD BE

8239
06:03:40,200 --> 06:03:43,280
FANTASTIC, IF WE COULD GET TO A

8240
06:03:43,280 --> 06:03:45,720
WIN THAT WOULD BE AMAZING. HOW

8241
06:03:45,720 --> 06:03:50,600
TO GET THERE IS NOT CLEAR BUT

8242
06:03:50,600 --> 06:03:51,800
REALLY APPRECIATED THE

8243
06:03:51,800 --> 06:03:52,960
THOUGHTFUL DISCUSSION AND IN

8244
06:03:52,960 --> 06:03:55,840
TERMS OF THE NEW OPPORTUNITIES

8245
06:03:55,840 --> 06:03:58,440
MANY OF YOU TALKED ABOUT FUTURE

8246
06:03:58,440 --> 06:04:00,160
IN WHICH COMBINATION THERAPIES

8247
06:04:00,160 --> 06:04:02,920
ARE BEING APPLIED AND EXAMINED

8248
06:04:02,920 --> 06:04:04,520
IN RIGOROUS WAYS WE HAVE A LOT

8249
06:04:04,520 --> 06:04:06,400
OF WORK TO DO TO GET THERE. THE

8250
06:04:06,400 --> 06:04:08,400
COMMENTS ABOUT IPSCs WERE

8251
06:04:08,400 --> 06:04:12,760
INTERESTING AND I THOUGHT THAT

8252
06:04:12,760 --> 06:04:13,920
COMMENTS ABOUT SOME OF THE NOVEL

8253
06:04:13,920 --> 06:04:15,680
GENE THERAPY EDITING APPROACHES

8254
06:04:15,680 --> 06:04:18,840
WERE REALLY EXCITING. SYNTHETIC

8255
06:04:18,840 --> 06:04:23,360
GENE CIRCUITS, SO WE ARE ALREADY

8256
06:04:23,360 --> 06:04:24,760
SEEING REALLY EXCITING

8257
06:04:24,760 --> 06:04:27,280
INNOVATIVE APPROACHES IN THIS

8258
06:04:27,280 --> 06:04:29,840
AREA. THANK YOU AMYE FOR

8259
06:04:29,840 --> 06:04:32,720
BRINGING US BACK TO CENTER OF

8260
06:04:32,720 --> 06:04:36,840
THE UNIVERSE. PATIENT HERE. SO

8261
06:04:36,840 --> 06:04:38,480
IMPORTANCE OF PATIENT

8262
06:04:38,480 --> 06:04:39,880
ENGAGEMENT, GOOD PATIENT

8263
06:04:39,880 --> 06:04:44,560
COMMUNICATION CHARACTERIZED BY

8264
06:04:44,560 --> 06:04:46,360
TRANSPARENCY, THAT WAS

8265
06:04:46,360 --> 06:04:47,560
CRITICALLY IMPORTANT. LASTLY TOO

8266
06:04:47,560 --> 06:04:49,960
I WANT TO SAY HOW FORTUNATE WE

8267
06:04:49,960 --> 06:04:52,200
WERE TO HAVE LARISSA HERE FROM

8268
06:04:52,200 --> 06:04:54,440
THE FDA. I LEARNED A LOT FROM

8269
06:04:54,440 --> 06:04:56,120
THAT ONE PRESENTATION, HOPEFULLY

8270
06:04:56,120 --> 06:04:58,960
Y'ALL FOUND THAT HELPFUL AS

8271
06:04:58,960 --> 06:05:00,560
WELL. I DON'T KNOW WHAT ELSE TO

8272
06:05:00,560 --> 06:05:02,800
SAY EXCEPT THANK YOU, THANK YOU 

8273
06:05:02,800 --> 06:05:06,360
THIS WAS REALLY GREAT DISCUSSION

8274
06:05:06,360 --> 06:05:08,680
ABOUT IMPORTANT COMPLICATED

8275
06:05:08,680 --> 06:05:12,000
TOPIC. SO THEN PERHAPS ONNA

8276
06:05:12,000 --> 06:05:13,480
NOTE, I DON'T KNOW WHETHER

8277
06:05:13,480 --> 06:05:15,720
JONELLE OR TED WERE PLANNING ON

8278
06:05:15,720 --> 06:05:18,120
LAST WORDS BUT REALLY ENJOYED

8279
06:05:18,120 --> 06:05:18,320
THIS.

8280
06:05:18,320 --> 06:05:19,760
>>JUST WANT TO THANK
LEADERSHIP

8281
06:05:19,760 --> 06:05:25,600
FOR THE SUPPORT AND LONG TIME

8282
06:05:25,600 --> 06:05:26,520
SUPPORT ONE AND A HALF YEARS TO

8283
06:05:26,520 --> 06:05:29,920
MAKE THIS HAPPEN. THANKS TO

8284
06:05:29,920 --> 06:05:32,160
PARTICIPANTS TO FOR YOUR

8285
06:05:32,160 --> 06:05:33,560
CONTRIBUTIONS AND YOUR

8286
06:05:33,560 --> 06:05:34,800
COMPROMISE, YOU ARE WILLING TO

8287
06:05:34,800 --> 06:05:37,000
TAKE OUR ASSIGNMENT. AND I

8288
06:05:37,000 --> 06:05:39,200
APPRECIATE IT. I THINK THIS IS A

8289
06:05:39,200 --> 06:05:40,400
VERY GOOD ROUND TABLE

8290
06:05:40,400 --> 06:05:42,680
DISCUSSION. THANK YOU ALL.

8291
06:05:42,680 --> 06:05:44,360
>>THANK YOU, TED. 

8292
06:05:44,360 --> 06:05:46,480
>>THANKS TO CONNIE AND
SCOTT. 

8293
06:05:46,480 --> 06:05:51,520
>>ABSOLUTELY. THANK YOU.

8294
06:05:51,520 --> 06:05:53,000
>>I THINK WHAT WE SHOULD
DO

8295
06:05:53,000 --> 06:05:56,400
MOVING FORWARD IS TAKE A DAY OR

8296
06:05:56,400 --> 06:05:58,240
TWO A WEEK OR MONTH AND THINK ON

8297
06:05:58,240 --> 06:06:02,000
THIS AND COMMUNICATE VIA EMAIL M

8298
06:06:02,000 --> 06:06:03,080
IF SOMETHING DOES COME OUT OF

8299
06:06:03,080 --> 06:06:04,400
THIS PUT YOUR THOUGHTS DOWN AND

8300
06:06:04,400 --> 06:06:06,280
EMAIL TO THE GROUP. IF YOU HAVE

8301
06:06:06,280 --> 06:06:09,920
RANDOM THOUGHTS HOW WE MIGHT --

8302
06:06:09,920 --> 06:06:11,720
WHAT CONCLUSION REACHED HERE AND

8303
06:06:11,720 --> 06:06:13,480
IMPORTANTLY ACTION ITEMS, WHAT

8304
06:06:13,480 --> 06:06:14,760
ARE THE REAL PRIORITIES MOVING

8305
06:06:14,760 --> 06:06:19,440
FORWARD. WE TALKED ABOUT SOME

8306
06:06:19,440 --> 06:06:20,400
BUT ANY IDEAS THAT COME UP

8307
06:06:20,400 --> 06:06:23,720
PLEASE SHARE WITH US.

8308
06:06:23,720 --> 06:06:25,480
>>THANK YOU JONELLE.

8309
06:06:25,480 --> 06:06:27,920
>>THANK YOU TO EVERYBODY.
I'M

8310
06:06:27,920 --> 06:06:31,920
SORRY, I CUT YOU OFF, DR. CHU.

8311
06:06:31,920 --> 06:06:33,160
>>DAVID AND EVERYONE,
THANK YOU

8312
06:06:33,160 --> 06:06:35,360
SO MUCH.

8313
06:06:35,360 --> 06:06:38,920
>>I WAS JUST GOING TO SAY

8314
06:06:38,920 --> 06:06:41,600
MEETING IS ADJOURNED, HOPE

8315
06:06:41,600 --> 06:06:42,720
EVERYTHING HAS A PLEASANT

8316
06:06:42,720 --> 06:06:44,440
EVENING DEPENDING ON WHAT TIME

8317
06:06:44,440 --> 06:06:48,120
ZONE YOU ARE IN.

8318
06:06:48,120 --> 06:06:58,600
>>WE WILL SEND PICTURES. 

8319
06:07:00,440 --> 06:07:04,800
>>THANKS FOR TECHNICAL
SUPPORT

8320
06:07:04,800 --> 06:07:05,800
OF DAVID.

8321
06:07:05,800 --> 00:00:00,000
>>GOOD NIGHT.  EVERYBODY.