Background: Mesenchymal stem-cell (MSC) therapy for perianal fistulas in Crohn's disease (CD) remains controversial. We performed this meta-analysis to evaluate the efficacy and safety of MSC therapy for the treatment of perianal fistulas in CD.
Methods: Electronic databases were searched for studies that reported efficacy and/or safety of MSC therapy for perianal CD (pCD). We used the metaprop command of the meta package in R and RevMan to assess the efficacy and safety. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.
Results: After screening, 13 trials were included in our study. RevMan for meta-analysis showed that: (1) patients had healed perianal fistulas after MSC treatment, with an odds ratio (OR) of 2.05 (P = 0.0002; 95% confidence interval (CI) 1.41, 3.00) vs controls; (2) pelvic magnetic resonance imaging (MRI) used to evaluate the healing of fistulas showed that MSC therapy had a higher healing rate (HR) compared to control (OR = 1.95; P = 0.0007; 95% CI 1.33, 2.87). R software for meta-analysis showed that 63% (95% CI 0.53, 0.74) of patients achieved clinical healing as a result of local therapy with MSCs. Random-effects pooled rates of clinical response were 30% (95% CI 0.18, 0.48). Pelvic MRI used to evaluate fistula healing showed a HR of 56% (95% CI 0.46, 0.69). The HR with autologous MSCs was higher than with allogeneic MSCs (79% vs 52%; P < 0.05). Uniform injection of MSCs according to the size of fistulas improve the HR (80% vs 55%; P < 0.05) compared with fixed-dose MSCs. There was no significant increase in adverse events (OR = 1.14; P = 0.54; 95% CI 0.75, 1.74) in patients treated with MSCs and no major MSC-related adverse event has been reported so far.
Conclusions: Local administration of MSCs is an effective and safe method for pCD. It also represents hope for effective treatment of refractory pCD.
Keywords: Adverse effects; Crohn’s disease; Efficacy; Mesenchymal stem cells; Meta-analysis; Perianal fistula.