research today, this is a quest that's been about 11 years in the making. It's a multi-center trial between the Kuala Lumpur Sports Medicine Center, which is in Kuala Lumpur, Malaysia, and the Andrews Institute, which is in Gulf Breeze, Florida. As disclosures, this study was sponsored by KLSMC Stem Cells, Incorporated, and grants from the city of Gulf Breeze, Florida, and the state of Florida. Large cartilage defects still remain an unresolved clinical problem. Dr. Kayoung Song is an orthopedic surgeon from Kuala Lumpur Sports Medicine Center in Malaysia, who's been developing a technique utilizing autologous stem cells. The idea is to regenerate articular cartilage utilizing an autologous cell source that's been around for decades within the hematology-oncology population. This KLSMC Articular Cartilage Regeneration Technology, or CART for short, involves four phases. The first is subchondral drilling, which is marrow stimulation just performed much closer together and much deeper. This arthroscopic procedure is followed by a cell harvest at one time point that's similar to how you harvest for a bone marrow transplant. Subjects are given neupogen for three days to mobilize the cells from their bone marrow to peripheral circulation, and then harvested with an apheresis machine, which is similar to hemodialysis, only different and used in the hem-onc world for bone marrow transplant harvest. We then process that product in a clean room, a C-GMP-compliant facility, where you prepare it for cryopreservation so that we can do multiple post-operative injections during the whole healing phase of the tissue. There's a series of five injections that starts three weeks, one through five, and then a series of three at six months, a series of three at 12 months, and a series of 18 months, similar to the idea of refertilizing or seeding your lawn after preparing it for repair. Then physical therapy is standard for what you would expect for marrow stimulation procedures, CPM, and static loading of the tissue. This technology has been developing from the bench to the bedside since 2009 with an animal model published in Arthroscopy, followed by a case series published in 2011, a randomized control trial that was published in 2013 at one site, and then we initiated an FDA-observed multicenter trial with an IND in place. The study initiated in 2016 with the goal of enrolling 120 subjects. Inclusion criteria, there were nine, and exclusion 21. Subjects aged 18 to 55 years, they had to have at least one defect that was over 3 centimeters in size. Bipolar cartilage defects were allowed, PFGA cartilage defects were allowed, and previously failed cartilage repair procedures were allowed as well. Surgical considerations for exclusion were any kind of varus or valgus deformity that you would not accept, and a BMI over 35. Medical considerations as well, and we started in 2016 with a goal of 120 subjects. With the IND design, there was an interim analysis that was performed in 2019. At that time, we had assessed 109 subjects, we had excluded 40 and randomized 69, 33 of the control group, and the control group was hyaluronic acid and physical therapy compared to the CART procedure. At 12 months, we had lost two who had withdrawn from the control group and lost to follow-up one in the intervention group, so we analyzed 33 at the 24-month time point and 35 in the intervention group. Our primary outcome measures were IKDC and the KUS score for pain. IKDC reached statistical significance that was MCIDD significant at 18 months and at 24 months. The KUS pain subdome similarly reached statistical significance at 12 months, 18 months, and 24 months. Our secondary outcome scores was a morphologic MRI score, MOCART, and numeric rating scale pain score. The MOCART score showed statistical significance at 12 and 24 months after surgery with progressive healing of the tissue up to the 24-month time point in the intervention group. The NRS pain score showed progressive improvement in the intervention group with statistical significance as early as six months. In conclusion, for large, complex cartilage defects, this multicenter randomized control trial applying CART to HA and physical therapy showed it to be safe and significant improvements in our clinical scores and our radiologic scores. I have to say thank you to multiple people for this study, not only the co-authors who are on it, but also some of my research mentors who are in this room. Brad Bushnell, who presented in the last session, got me started in research many years ago. And then Gary Poehling, who's here as well, first sent me to Malaysia in 2009. I went in 2009 and then also as a fellow in 2011. And since we started this multicenter collaboration at that time, they figured that it was acceptable for a resident fellow research award, which we won this year for this paper. Also, thank you to everybody at the Andrews Institute who supported this, including Dr. Andrews and Chad Gilliland. And I have to say thank you to my wife, because along this whole 11-year quest, she hasn't wavered in terms of her support of me doing it. Thanks for your attention. Thank you.

multicenter trial

Kuala Lumpur Sports Medicine Center

Andrews Institute

autologous stem cells

articular cartilage regeneration