Mesenchymal stem cell-derived exosomes for complex perianal fistula ‒ A systematic review and single-arm meta-analysis.

Objectives: We performed a single-arm meta-analysis to evaluate the efficacy and safety of MSC-Exos in the treatment of complex PFs.

Methods: This systematic review followed PRISMA guidelines and included studies published up to March 20, 2025. We searched four databases for studies evaluating efficacy and/or safety of MSC-Exos for complex PFs. Analyses were performed using R statistical software version 4.4.0.

Results: The analysis of three studies included in this study suggested that MSC-Exos were effective in achieving complete healing in 57% of patients with complex PFs (95% confidence interval (CI) 0.43, 0.76). The pooled data further indicated that MSC-Exos could achieve complete healing in 68% of complex fistula tracts (95% CI 0.59, 0.80). Pooled analysis also showed that 86% (95% CI 0.75,0.98) of patients with complex PFs achieved clinical response post treatment, whereas 18% (95% CI 0.09, 0.37) demonstrated no clinical response after MSC-Exos treatment. Subgroup analysis revealed a higher healing rate (HR) in patients with Crohn's disease (CD) compared to those without CD (60% vs. 57%, respectively), with no statistically significant differences (P > 0.05). Notably, neither systemic nor local adverse effects have been reported in any study.

Conclusion: This meta-analysis highlights the efficacy and safety of local administration of MSC-Exos in patients with complex PFs, offering valuable evidence to guide future clinical practice.