Long-term clinical outcomes of stem cell-based interventions in Crohn's-related perianal fistula: A systematic review...

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.

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.

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 (I² = 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.

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.