Intra articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)
AbstractBackgroundMesenchymal stromal cells are a promising option to treat knee osteoarthritis. Their safety and usefulness must be confirmed and the optimal dose established. We tested increasing doses of bone marrow mesenchymal stromal cells (BM MSCs) in combination with hyaluronic acid in a randomized clinical trial.MaterialsA phase I/II multicenter randomized clinical trial with active control was conducted. Thirty patients diagnosed with knee OA were randomly assigned to intraarticularly administered hyaluronic acid alone (control) or together with 10 x 106 or 100 x 106 cultured autologous BM MSCs, and followed up for 12 months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X ray and magnetic resonance imaging analyses were performed to analyze joint damage.ResultsNo adverse effects were reported after BM MSC administration or during follow up. BM MSC administered patients improved according to VAS during all follow up evaluations and median value (IQR) for control, low dose and high dose groups change from 5 (3, 7) 7 (5, 8) and 6 (4, 8) to 4 (3, 5) 2 (1, 3) and 2 (0,4) respectively at 12 months (low dose vs control group p 0.005 and high dose vs control group p 0.009) BM MSC administered patients were also superior according to WOMAC, although improvement in control and low dose patients could not be significantly sustained beyond 6 months. On the other hand, the BM MSC high dose group exhibited an improvement of 16.5 (12, 19) points at 12 months (p 0.01) Consistent with WOMAC and VAS values, motion ranges remained unaltered in the control group but improved at 12 months with BM MSCs. X ray revealed a reduction of the knee joint space width in the control group that was not seen in BM MSCs high dose group. MRI (WORMS protocol) showed that joint damage decreased only in the BM MSC high dose group, albeit slightly.ConclusionsThe single intraarticular injection of in vitro expanded autologous BM MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when 100 x 106 cells are administered. These results pave the way for a future phase III clinical trial. Clinical Trials.gov identifier NCT02123368. No EudraCT: 2009 017624 72
Journal of Translational Medicine