Mesenchymal stem-cell therapy for perianal fistulas in Crohn's disease: a systematic review and meta-analysis

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.