METHODS: This umbrella review was conducted following the Joanna Briggs Institute (JBI) methodology to assess the efficacy and safety of stem cell therapy for treating various types of fistulas. A comprehensive search was performed across multiple electronic databases including PubMed, Embase, Cochrane Register, and Web of Science up to May 5th, 2024. Systematic reviews focusing on stem cell therapy for fistulas were included, with data extracted on study design, stem cell types, administration methods, and outcomes. The quality of the reviews was assessed using the AMSTAR 2 tool, and meta-analyses were conducted using R software version 4.3.

RESULTS: Nineteen systematic reviews were included in our umbrella review. The stem cell therapy demonstrated by significant improvements in clinical remission rates, with a relative risk (RR) of 1.299 (95% CI: 1.192 to 1.420). Stem cell therapy enhanced fistula closure rates, both short-term (RR=1.481; 95% CI: 1.036 to 2.116) and long-term (RR=1.422; 95% CI: 1.091 to 1.854). The safety analysis revealed no significant increase in the risk of adverse events with stem cell therapy, showing a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for general adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events, both of which indicate a safety profile comparable to control treatments. Re-epithelialization rates also improved (RR=1.44; 95% CI: 1.322 to 1.572).