Mesenchymal stem cell-derived extracellular vesicles for osteochondral defect regeneration: a systematic review and meta-analysis of preclinical studies

BACKGROUND: In recent years, the number of animal studies investigating mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy for osteochondral defects has steadily increased. However, a comprehensive and systematic quantitative analysis is lacking. This meta-analysis aimed to evaluate the efficacy of MSC-EVs in animal models of osteochondral defect through a meta-analysis. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched up to January 31, 2025, to identify and select preclinical studies on MSC-EVs therapy for osteochondral defect models. No restrictions were applied regarding the specific characteristics of MSC-EVs or animal models. A random-effects model was used to perform pooled analyses of osteochondral repair scores, bone structural parameters, and histological scores. Subgroup analyses were conducted to explore potential sources of heterogeneity. Sensitivity analyses, funnel plots, and Egger's test were employed to assess the robustness and stability of the results. RESULTS: A total of 19 studies met the inclusion criteria. MSC-EVs intervention improved International Cartilage Repair Society (ICRS) and Modified O'Driscoll Scale (MODS) scores at both 3 and 6 months, and significantly increased BV/TV, Tb.Th, as well as histological scores of cartilage and subchondral bone. Subgroup analyses indicated that none of the examined subgroups were significant sources of heterogeneity. Sensitivity analyses demonstrated the robustness of the results. CONCLUSIONS: MSC-EVs improved osteochondral repair scores, bone structural parameters, and histological outcomes in preclinical models, indicating their potential for promoting osteochondral regeneration. However, the evidence is primarily derived from small animal models with methodological variability and publication bias. Future studies should focus on large-animal models, standardized EVs preparation and dosing protocols, and long-term safety evaluations to facilitate clinical translation.