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)

Abstract

BackgroundMesenchymal 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 × 106 or 100 × 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 × 106 cells are administered. These results pave the way for a future phase III clinical trial.Clinical Trials.gov identifier NCT02123368. Nº EudraCT: 2009-017624-72Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0998-2) contains supplementary material, which is available to authorized users.

MSC Therapy for Osteoarthritis: An Unfinished Story

“…For example, some studies focus on expanded cell preparations and some on unexpanded concentrates. Some studies utilize expanded cells from adipose, marrow, or umbilical cord . Some studies utilize allogeneic cells sources and others use autologous strategies.…”

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II)

“…Mesenchymal stromal cells are a promising option to treat knee osteoarthritis (OA) where, to date, knee arthroplasty is the only therapeutic option [3]. In the short term, the safety and usefulness of single injection of expanded autologous MSCs have been reported with positive results [4–6]. However, long-term results on the efficacy of MSCs in patients with osteoarthritis have been scarcely reported.…”

“…gov identifier: NCT02123368) of patients with knee osteoarthritis previously reported [4]. The occurrence of complications and/or adverse effects during the clinical study was registered.…”

International Forum on GMP‐grade human platelet lysate for cell propagation

“…We culture mesenchymal stem cells with HPL for different clinical trials, mainly for the treatment of complications of the hematopoietic stem cell transplant (graft‐versus‐host disease or cytopenias) or for orthopaedic diseases . The final concentration of HPL in the culture medium is 5%.…”