Exploring the effectiveness and safety of stem cell therapy for repair of cartilage defects: a meta-analysis of randomized controlled trials.

BACKGROUND

Osteoarthritis (OA) is one of the most common degenerative joint diseases worldwide, characterized by chronic pain, functional impairment, and progressive cartilage loss. Mesenchymal stem cells (MSCs) therapy has emerged as a promising regenerative strategy due to its chondrogenic and immunomodulatory properties. Although randomized controlled trials (RCTs) have generally demonstrated favorable therapeutic effects, differences in study design, patient characteristics, and treatment protocols have resulted in substantial clinical and methodological heterogeneity. Therefore, an updated meta-analysis is needed to comprehensively evaluate the efficacy and safety of MSC therapy.

OBJECTIVE

To systematically assess the efficacy and safety of stem cell therapy compared with control interventions in patients with OA with primary emphasis on pain, functional outcomes, cartilage regeneration, and adverse events, and to identify potential factors influencing therapeutic outcomes.

METHODS

A comprehensive search of PubMed, Web of Science, Embase, Medline, Scopus, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) published up to 1 August 2025. Clinically relevant outcomes included pain, WOMAC, KOOS subscales, cartilage volume, and adverse events, which were analyzed as key outcome domains reflecting pain, function, structural change, and safety in osteoarthritis. Meta-analysis was conducted using STATA version 15.1 (StataCorp, College Station, TX, United States) to estimate standardized mean differences (SMDs) or odds ratios (ORs) with 95% confidence intervals (CIs). Random-effects models, predefined subgroup analyses, and risk-of-bias assessments were performed.

RESULTS

A total of 24 randomized controlled trials involving 1,389 patients were included. Compared with control interventions, MSC therapy significantly improved pain (SMD = -1.31, 95% CI: -1.82 to -0.81), WOMAC scores (SMD = -0.78, 95% CI: -1.09 to -0.47), cartilage volume (SMD = 0.91, 95% CI: 0.28-1.53), and KOOS subscales. No significant difference was observed in adverse event rates (OR = 1.58, 95% CI: 0.72-3.47). Subgroup analyses suggested that treatment response may vary according to disease etiology, stem cell source, tissue origin, and delivery strategy; however, these findings were exploratory and should be interpreted cautiously because substantial residual heterogeneity remained across several outcomes.

CONCLUSION

MSC therapy was associated with significant improvements in pain, physical function, cartilage volume, and KOOS outcomes without an apparent increase in adverse events. However, substantial heterogeneity across studies and the exploratory nature of subgroup analyses warrant cautious interpretation of these findings. Further large-scale randomized controlled trials with standardized treatment protocols and long-term follow-up are required to confirm the optimal therapeutic strategy and long-term efficacy and safety of MSC therapy.