PRP, Stem Cells and More Management of OA and Cartilage Defects I (and/or my co authors) have something to disclose. Detailed disclosure information is available via: Brian J. Cole, MD, MBA Professor and Vice-Chairman, Department of Orthopedics Chairman of Surgery, Rush OPH Section Head, Rush Cartilage Restoration Center Team Physician, Chicago White Sox and Bulls The course syllabus, or AAOS Disclosure Program on the AAOS website at http://www.aaos.org/disclosure Biologics PRP Biocartilage MSCs Overview Rationale for Biologics Alone or as an adjunct to surgery Anabolic and anti-catabolic molecules that modify the arthritic or regenerative process Cartilage Synovium MSCs Subchondral bone Boswell, Fortier, Cole, Arthroscopy 2011 Wishful Thinking Are we really regenerating anything? 1
PRP Regulatory Process PRP and Cartilage FDA Position CBER (CFR 1271) Exempt from study 510(k) for centrifuge PRP to be used with bone graft to enhance bone graft handling properties AJSM 2013 OA and Cart, 2010 Plasma Buffy Coat RBCs ACP HA B-meth Ctx Matrix synthesis Chondrogenesis Decrease pain Anti-inflammatory HA synthesis Anti-infective PRP and MSCs JKS 2012 JOR, 2014 Arthroscopy, 2015 Why does microfracture fail? MSCs to serum MSCs to PRP Benefits of Collagen JOR 2011 JSES 2015 Pre Micfx Awl Post Micfx Awl Intact Surgical Control PowerPick Mcfx Microfracture Collagen Scaffold 2
BioCartilage AJSM 2016 Micronized cartilage scaffold Aseptically processed w 5 year shelf-life Mix into paste with PRP or BMC Retention of: ECM: Type II collagen, Aggrecan, Decorin IHC staining for type II collagen GF: TGF, FGF, PDGF, VEGF, BMP-7, EGF, IGF, etc. In vivo model Five horses, two 10 mm defects/knee Microfracture +- Biocartialge Outcomes Arthroscopic 2, 6, and 13 months Gross, MRI, uct, and Histology 2 nd Look Arthroscopy 2 mo 6 mo 13 mo Macro and MRI Microfracture Biocartilage Microfx BioCartilage Type II Collagen Staining Microfracture Biocartilage Case Example Defect Evaluation 24 yo NFL lineman in contract year Years of medial pain 3
Microfracture Biocartilage/PRP/BMAC 1 year post op MRI AJSM 2013 PRP and OA It doesn t work! Arthroscopy, 2011 It works! Arthroscopy, 2012 It might work! AJSM, 2012 AJSM, 2013 4
AJSM 2016 AJSM 2016 Safety and efficacy of LP-PRP vs Saline 15/group 3 weekly inj PRDBCT HA (50) vs ACP (50) All w blood draw US aspiration and injection Clinical/Biochemical Outcomes Improvement @ 12 mo 78% vs 7% WOMAC Results Results Responders Low BMI < 25 vs > 34 K-L < Grade 2 0-100 70 65 60 55 50 45 40 VAS PRP HA PRP fold not a factor 35 30 1 5 9 13 17 21 25 29 33 37 41 45 49 Time (Weeks) Less pain at 6 mo and 1 year w/ PRP p=0.009 at 6 month (VAS 34 vs 48) p=0.004 at 1year (VAS 43 vs 57) LP vs LR PRP and OA Combination PRP + HA LP-PRP better than HA, LR-PRP AJSM 2015 and Placebo Plos One (2016) Biomaterials (2014) Am J Sports Med (2016) 5
My Algorithm for OA Stem Cells Yes 1 st injection +- HA Response? No DREAM 1-2 weeks 2 nd injection Response? No STOP? Yes?? 3 nd injection OR REALITY? Their language is intentionally imprecise and exploits the vulnerability of patients with debilitating diseases How do they work? Medicinal Signaling Cells The U.S. has the world s highest density of online stem-cell tourism in the world 1. Recruit other stem cells 2. Secrete bioactive factors Angiogenesis Mitosis Anti-scaring Anti-apoptotic 3. Local modulation Anti-inflammatory Immunomodulatory - Reduce T cell surveillance Bunnell. Stem Cell Res and Therapy, 2010. MSC Strategies Cultured BM MSCs in OA and FCD WHERE? WHAT? BONE MARROW, ADIPOSE TISSUE, SYNOVIUM, PERIPHERAL BLOOD CONCENTRATED OR EXPANDED Stem Cells, 2014 HOW? IA INJECTION OR SURGICAL DELIVERY Cultured Marrow MSCs Improved Clinical Improved MOCART Cultured Adipose MSCs Improved WOMAC Decreased defect size increased cartilage volume AJSM, 2010 ACI (N= 36) vs Cultured BMSCs (N=36) Similar clinical and MRI 1 vs 2 surgery advantage 6
351 Classified Product Cultured BM MSCs and FCD BMAC Why Concentrate BM? EPCs, HSCs and MSCs 14 x concentration 30K in 50 cc BMA Phenotypic stability PRP made from BM with MSCs w increased WBCs and less fibrinogen BMA at 96 hrs BMC at 96 hrs Courtesy Dr. Mazzoca UCONN Does BMC make sense in OA? BMAC has IL1-ra BMA BMC PRP IL-1ra ++ ++++ + IL-1ra :IL-1β - + - IL-1Ra/IRAP/Orthokine MSC + ++ - TGF-β1, PDGF + ++ +++ Il-1β, IL-8 + ++ - Fortier, Kennedy, et al KSSTA, in press 7
International Orthopedics, 2015 7 Studies in 314 Patients w Knee OA Jadad Scale (quality): 3 High and 4 Low Source 4 BMC, 2 Adipose, 1 Cord Blood Results Pain: No or inconclusive impact Function: MSCs alone or combined improved function at 3, 12, and 24 mo (inconclusive vs hyaluronic acid) Evidence weak w heterogeneous patients and low quality, incomplete outcomes and small sample sizes AJSM, 2016 Systematic review of BMAC for FCD or OA 11 Studies 5 Prospective 1 Retrospective 5 Case Series/Reports 3 Studies for OA 8 Studies for FCD Paucity of high quality studies, BMAC safe, recommend judicious use until better evidence exists AJSM, 2015 AJSM, 2016 B/L knee OA/Pain tx w BMAC/PPP in one and saline in other (N=25) Dramatic pain relief in both, but no differences between them (NS) Conclusions 1st Annual AOSSM OLC Biologics/US Course October 12-13, 2018 Chicago, IL 1st Annual AANA Practice Management Course November 8-9, 2018 Chicago, IL BioCartilage for any defect that you might consider MST as a scaffold delivery for PRP/MSCs LP PRP for OA is becoming a dominant treatment strategy FDA regulatory process of MSCs is a moving target with increasing oversight and business risk aversion as therapeutic options expand BMC for OA basic science supports it but clinical evidence lacking at this time 20 th Annual AANA/AOSSM/AAOS SKI COURSE January 30-February 3, 2019 Park City, Utah 8