Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis

Abstract

Background Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 × 106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial. Methods A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100 × 106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. Results No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. Conclusions Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Trial registration Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23

Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis

“…The control interventions in the rest trials were hyaluronic acid injection in five trials [ 15 , 157 , 160 , 163 , 175 ], PRP injection in four trials [ 161 , 167 , 168 , 172 ], saline injection in four trials [ 19 , 163 , 164 , 176 ], total knee arthroplasty in one study [ 162 ], and conservational treatment [ 18 ]. Combined therapy included total knee arthroplasty [ 162 ], PRP [ 161 ], PRP with arthroscopic debridement [ 172 ], and hyaluronic acid [ 160 ]. Most included individuals had grade II–III of Kellgren-Lawrence.…”

Autologous stem cell therapy in knee osteoarthritis: a systematic review of randomised controlled trials

“…38 40 In the trial of Lamo-Espinosa et al the intervention group received a single injection MSC+PRP followed by 2 PRP injections after 1 and 2 weeks. 38 Patients in the control group were treated with three single PRP injections in 3 weeks. After 1 year, there were no statistical significant differences in VAS and WOMAC scores between groups.…”

Bone Marrow Aspirate Concentrate Is More Effective Than Hyaluronic Acid and Autologous Conditioned Serum in the Treatment of Knee Osteoarthritis: A Retrospective Study of 505 Consecutive Patients

“…BMAC has been found superior to HA and ASC in the present study, showing an effect of treatment even at a 12-month follow-up; it was most effective in patients with higher grade knee OA. A potential explanation may be that the pluripotent stem cells present in BMAC are able to promote chondrogenesis and cartilage regeneration [23,26,32,34,39]. In addition, these cells can secrete certain growth factors resulting in an anti-inflammatory and immunomodulating effect on the knee, which may slow down or even prevent OA progression [40].…”