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 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 and 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 or minus fibrin glue) 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 those 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 versus 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 effective for perianal fistulas in CD. In addition, this treatment has favorable long-term efficacy and safety profiles.