Abstract
Abstract
Background
Perianal fistulas are a debilitating complication of Crohn's disease, frequently refractory to conventional medical and surgical therapy. Stem cell–based interventions, particularly mesenchymal stem cells (MSCs), have emerged as a promising therapeutic alternative, yet long‐term outcomes remain uncertain.
Methods
Web of Science, PubMed, Embase, Scopus, and the Cochrane Library were searched through September 1, 2024. Studies evaluating stem cell or stem cell‐derived products for Crohn's disease–associated perianal fistulas with ≥12 months' follow‐up were included. Efficacy outcomes included clinical and radiological healing and recurrence; safety outcomes encompassed adverse events, infections, malignancies and mortality. Meta‐analyses were conducted using random‐effects models. The primary analysis was restricted to RCTs, while observational and early‐phase studies were analysed separately. An exploratory pooled estimate across all study designs was also performed.
Results
Eighteen studies comprising 750 patients were included, with follow‐up ranging from 12 months to 4 years. In the primary analysis of RCTs, the pooled long‐term healing rate was 59% (95% CI, 51%–67%), with no observed heterogeneity (
I
2
= 0%). Observational and early‐phase studies demonstrated broadly comparable healing rates but with greater heterogeneity and a higher risk of bias. An exploratory pooled analysis across all studies yielded an overall healing rate of 63% (95% CI 55%–70%), although this estimate should be interpreted with caution due to differences in study design. Safety profiles were favourable across studies. No treatment‐related deaths and no definitively therapy‐associated malignancies were identified.
Conclusions
Stem cell‐based therapy is a safe and effective long‐term treatment option for Crohn's disease associated perianal fistulas, achieving durable closure in approximately two‐thirds of patients.