Systematic review with meta-analysis: the efficacy and safety of stem cell therapy for Crohn's disease

Background and aims: Stem cell therapy (SCT) for the treatment of Crohn's disease (CD) is still in its infancy, and whether SCT is associated with improved outcomes is unclear. We performed a meta-analysis to evaluate the efficacy and safety of patients receiving SCT. Methods: Electronic databases were searched for studies that reported the use of stem cells for the treatment of patients with CD. Raw data from included studies were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes. Results: We analyzed 21 studies comprising 514 patients with active CD. A random-effects meta-analysis of studies of SCT as systemic infusion showed 56% (95% confidence interval (CI) 33-76, n = 150) of patients achieved clinical response. Similarly, random-effects pooled rates of clinical or endoscopic remission were 46% (95% CI 25-69, n = 116) and 15% (95% CI 0-50, n = 48), respectively. A random-effects meta-analysis of all perianal CD studies showed that 57% (95% CI 44-69%, n = 251) of patients had healed fistula with SCT, with an odds ratio of 3.83 (95% CI 1.06-13.86, n = 121, P = 0.04) versus control. The pooled rate of clinical recurrence was high at 16% (95% CI 4-34, n = 101) with follow-up > 12 months. The pooled rates of severe adverse events (SAEs) and SAEs related to SCT were 12% (95% CI 6-23, n = 378) and 8% (95% CI 3-18, n = 378), respectively. The Egger test suggests no publication bias existed for fistula healing (P = 0.36), but did for clinical response (P = 0.003). Conclusions: SCT seems potentially effective and may serve as an alternative treatment for refractory active CD. Toxicity will remain the most significant barrier to systemic SCT in patients with CD.