Published online Jul 26, 2026. doi: 10.4252/wjsc.122048
Revised: May 13, 2026
Accepted: June 18, 2026
Published online: July 26, 2026
Processing time: 107 Days and 22.3 Hours
Fistula-related diseases are characterized by a chronic course, high recurrence rates, and limited therapeutic benefits. Conventional treatments are associated with suboptimal healing rates and substantial complication risks. Cell-based regenerative therapies have attracted increasing attention due to their combined immunomodulatory and tissue-repair properties. However, evidence regarding their overall efficacy and safety remains fragmented and heterogeneous.
To determine the overall efficacy and safety of cell-based regenerative therapies for fistula-related diseases through a systematic review and meta-analysis.
PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from database inception through December 15, 2025 to identify systematic reviews and meta-analyses examining regenerative therapies for fistula-related diseases. Review quality was appraised with A Measurement Tool to Assess Systematic Reviews 2, certainty of evidence was evaluated according to Grading of Recommendations, Assessment, Development and Evaluation, overlap among primary studies was measured using the corrected covered area, and visual evidence maps were generated.
Thirty-five eligible systematic reviews and meta-analyses were included, and most of the evidence concerned perianal fistulas (PF) and fistulizing Crohn’s disease (FCD). Mesenchymal stem cells (MSCs) were the most frequently evaluated intervention, whereas evidence for platelet-rich plasma (PRP), MSC-derived exosomes, and hematopoietic stem cells (HSCs) was limited. Across PF and FCD, MSC-based therapy was generally associated with higher rates of combined remission, clinical and/or radiological healing, clinical remission, and clinical response than comparator treatments, although the strength and consistency of evidence varied across outcomes and reviews. Some findings were supported by moderate-certainty evidence, but most included reviews were rated as low or critically low confidence. Treatment effects appeared to differ according to cell source and delivery strategy, with adipose-derived, allogeneic, and locally injected MSC more often associated with favorable outcomes. MSC therapy did not increase the overall risk of adverse events (AE), and low-certainty evidence suggested that it may be associated with a reduced risk of serious AEs. Evidence for PRP, exosomes, and HSCs remained sparse and insufficient for firm conclusions.
Thirty-five eligible systematic reviews and meta-analyses were included, and most of the evidence concerned PF and FCD. MSCs were the most frequently evaluated intervention, whereas evidence for PRP, MSC-derived exosomes, and HSCs was limited. Across PF and FCD, MSC-based therapy was generally associated with higher rates of combined remission, clinical and/or radiological healing, clinical remission, and clinical response than comparator treatments, although the strength and consistency of evidence varied across outcomes and reviews. Some findings were supported by moderate-certainty evidence, but most included reviews were rated as low or critically low confidence. Treatment effects appeared to differ according to cell source and delivery strategy, with adipose-derived, allogeneic, and locally injected MSC more often associated with favorable outcomes. MSC therapy did not increase the overall risk of AEs, and low-certainty evidence suggested that it may be associated with a reduced risk of serious adverse events. Evidence for PRP, exosomes, and HSCs remained sparse and in
Core Tip: This umbrella review demonstrates that mesenchymal stem cells (MSCs) based regenerative therapy is associated with meaningful improvements in healing and remission in perianal fistulas and fistulizing Crohn’s disease. The most consistent benefits were observed with adipose-derived, allogeneic, and locally injected MSC. MSC therapy was generally well tolerated, with no increase in overall adverse events and potential reduction in serious adverse events. Among currently studied regenerative approaches, MSC appears to be the most promising option for fistula-related diseases.