Efficacy of stem cell therapy for achilles tendon rupture: a systematic review and meta-analysis based on animal studies.

Background: Although stem cell-based therapies show promise for promoting Achilles tendon regeneration, the current preclinical evidence is highly heterogeneous, and their overall efficacy and key modifying factors remain unclear. Methods: We systematically searched PubMed, Web of Science, Embase, and Scopus for studies based on rat models of Achilles tendon rupture. Two investigators independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using R software. Results: Twenty-seven studies were included. Pooled analyses showed that stem cell transplantation significantly improved ultimate load and histological scores of the Achilles tendon, with effects increasing over time. However, the impact of stem cell therapy on tendon stiffness was limited. For type I collagen, stem cell transplantation alone did not significantly enhance its expression, whereas combining stem cells with biomaterial scaffolds led to a marked increase. Subgroup analyses revealed a complex relationship between stem cell dose and treatment efficacy: for ultimate load, a moderate dose was effective at 2 weeks, while a high dose was more effective at 4 weeks; for histological scores, both low and moderate doses were effective at 2 weeks, whereas only moderate-to-high doses were effective at 4 weeks, indicating a nonlinear and time-dependent dose-response pattern. Overall, composite strategies using scaffold-loaded stem cells were generally more effective than scaffold treatment alone. Assessment of publication bias suggested potential bias in the primary outcomes, but trim-and-fill correction did not materially alter the conclusions. Risk-of-bias evaluation showed generally inadequate reporting in key methodological domains, including random sequence generation, allocation concealment, and blinding, indicating a potential risk of bias. Conclusion: Stem cell transplantation can effectively improve the biomechanical strength and histological architecture of the Achilles tendon after rupture, but its effects on stiffness restoration and type I collagen expression appear limited. Based on early healing data from rat models, scaffold-loaded stem cell therapy shows potential for enhancing Achilles tendon repair. However, the current preclinical literature is characterized by methodological shortcomings and marked heterogeneity in critical factors such as stem cell sources and scaffold materials. As a result, the findings primarily reflect overall trends rather than definitive effects, and clinical translation will require further standardized studies and validation in large animal models.