Conclusion

This meta-analysis establishes the definitive structural efficacy of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in preclinical osteoarthritis models, demonstrating profound and highly robust cartilage protection across both human- and animal-derived sources. Crucially, rigorous publication bias analyses confirm these therapeutic signals are not artifacts of selective reporting. However, the pervasive methodological heterogeneity observed, specifically the reliance on arbitrary and incomplete dosing metrics, represents a critical translational barrier. The path forward for MSC-EV therapeutics does not lie in accumulating further basic efficacy data, but rather in adopting stringent ADMET and pharmacokinetic frameworks. By standardizing isolation procedures and reporting, harmonizing particle-to-biomolecule dosing ratios, and integrating precise in vivo clearance and biodistribution tracking, the field can successfully transition MSC-EVs from promising experimental biologics to safe, reproducible, and regulatory-approved advanced medicinal products (ATMPs).