Efficacy and safety of mesenchymal stem cells in the treatment of perianal fistulas in Crohn's disease: a meta-analysis of randomized controlled trials

Objectives: Local mesenchymal stem cell (MSC) therapy for perianal fistulas in Crohn's disease (CD) has yielded promising results, but it still remains controversial.In this study, we aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of both autologous or allogeneic MSC therapy for perianal CD (pCD).Methods: RCTs reporting MSC therapy for perianal fistulas in CD were searched and included.The effectiveness and safety data were analyzed using RevMan 5.3.Results: A total of 6 RCTs were included in this meta-analysis.The analysis showed that patients receiving MSC therapy (plus fibrin glue or not) presented a higher healing rate (HR) of pCD than those in the control group (fibrin glue or saline solution) (odds ratio (OR)=1.92;95% confidence interval (CI) 1.27, 2.90; P=0.002).Compared with placebo (saline solution), MSC therapy improved the HR of pCD (OR=1.82;95% CI 1.19, 2.78; P=0.006).In thous studies, our study confirmed that significant long-term efficacy at least 52 weeks post MSC therapy (OR=1.80;P=0.008; 95% CI 1.17, 2.78).When MRI was used to evaluate fistula healing, a pooled analysis showed that the MSC group achieved a higher HR than the control group (OR=1.99;95% CI 1.17, 3.38; P=0.01).Furthermore, no significant differences were observed between MSC therapy and placebo in terms of adverse events (AEs) (OR = 1.29; 95% CI 0.70, 2.36; P = 0.42).None of the AEs were judged to be related to MSC treatment. Conclusions:This meta-analysis of RCTs provided evidence that local MSC injection is safe and efficacious for perianal fistulas in CD.In addition, this treatment has favorable long-term efficacy and safety profiles.