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)

Abstract

BackgroundMesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the long-term effects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical effect.MaterialsA phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10 × 106 or 100 × 106 cultured autologous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse effects and clinical evolution, assessed using VAS and WOMAC scorings are reported.ResultsNo adverse effects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-administered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p = 0.01; High-dose vs Control group, p = 0.004). Patients receiving BM-MSCs also improved clinically according to WOMAC. Control group showed an increase median value of 4 points (− 11;10) while Low-dose and High-dose groups exhibited values of − 18 (− 28;− 9) and − 10 (− 21;− 3) points, respectively (Low-dose vs Control group p = 0.043). No clinical differences between the BM-MSCs receiving groups were found.ConclusionsSingle intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible procedure that results in long-term clinical and functional improvement of knee OA.

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

“…The use of co-adjuvants with BM-MSCs in the treatment of OA is a topic of interest. Some authors report functional and clinical improvement without the use of coadjuvants, and others report clinical improvement with the use of HA as an adjuvant for BM-MSCs, while the use of PRP as adjuvant is still controversial [28,33,34]. The clinical results published without co-adjuvants seems to be comparable with our results using BM-MSC and PRGF ® .…”

“…We present the results of a phase II clinical trial that followed a previous phase I clinical trial focused primarily on safety and feasibility, with promising secondary e cacy results using a dose of autologous 100 million BM-MSCs, and with a clinical improvement that remained in long-term follow-up [18,33].…”

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

“…The use of co-adjuvants with BM-MSCs in the treatment of OA is a topic of interest. Some authors report functional and clinical improvement without the use of coadjuvants, and others report clinical improvement with the use of HA as an adjuvant for BM-MSCs, while the use of PRP as adjuvant is still controversial [28,33,34].…”

CCL25‐Supplemented Hyaluronic Acid Attenuates Cartilage Degeneration in a Guinea Pig Model of Knee Osteoarthritis

“…It has been recently shown that single intra‐articular injection of in vitro expanded autologous bone marrow MSC is a safe and feasible method that results in long‐term clinical and functional improvement of knee OA . To avoid the long and costly culture period, we proposed a one‐step in situ repair approach using a potential trigger for recruitment of endogenous MSC into the OA side and thereby enhance regeneration. The results of this and other studies suggest that the chemokine CCL25 affects the migration of MSC.…”