Efficacy based on dose-response and safety of bone marrow-derived mesenchymal stem cells for the treatment of osteoarthritis: a systematic review and meta-analysis.

Abstract

<h4>Introduction</h4>In recent years, the use of mesenchymal stem cells (MSCs), especially those derived from bone marrow and embryonic sources, has been considered as an emerging therapeutic approach for repairing joint tissue and reducing osteoarthritis symptoms. This systematic review and meta-analysis evaluated bone marrow-derived mesenchymal stem cells (BM-MSCs) efficacy, safety, and optimal dosing for osteoarthritis treatment.<h4>Methods</h4>Thirteen randomized trials of the 1427 articles identified (11 meta-analyzed; n = 1150 patients) were identified via PubMed, Scopus, Embase, and other databases (search updated to May 2025). The primary outcomes were the optimal dose of BM-MSCs in improving pain intensity (VAS), WOMAC scores (pain, stiffness, function, total score), and their safety, analyzed using RevMan 5.4. Cochrane risk-of-bias assessment guided quality appraisal.<h4>Results</h4>BM-MSCs showed no significant pain reduction (VAS) or functional improvement (WOMAC) at 1-3 months' post-injection. Significant improvements emerged at 6 months, peaking at 12 months: VAS decreased by WMD - 2.31 (95% CI - 3.83 to - 0.80; P = 0.003), and WOMAC total score reduced by WMD - 10.14 (95% CI - 18.26 to - 2.02; P = 0.01). Subgroup analyses indicated optimal doses of ≤ 25 × 10⁶ cells for VAS improvement and ≤ 25 × 10⁶ or 25-50 × 10⁶ cells for WOMAC total score at 12 months. Safety profiles were favorable, with no serious adverse events reported in most studies.<h4>Conclusion</h4>Based on the findings of this meta-analysis, BM-MSCs, especially in the long term, can be effective in reducing pain, stiffness, and improving the quality of life of patients with osteoarthritis. Also, the favorable safety of these cells makes them a promising option in joint reconstruction treatments. However, due to the heterogeneity of studies and the lack of standardized information on the optimal dose, it seems necessary to conduct prospective studies with careful design and long-term follow-up.