Standard treatments for Crohn's disease (CD)-associated complex perianal fistulas are associated with high recurrence rates. The injection of allogeneic mesenchymal stem cells (MSCs) is intended to prevent repeated surgery.

An update search was conducted for the first update assessing the efficacy and safety of MSCs in refractory patients. Two randomized controlled trials (RCTs) comparing MSCs with placebo and three non-comparative observational studies were evaluated. Current evidence indicated that MSCs lead to improvements in combined remission up to 52 weeks after therapy, but no improvements in quality of life or response. Several (severe) adverse events were reported in the studies. The RCTs showed no increased incidence of adverse events in the intervention groups compared to placebo.

The confidence level of the evidence was very low to low. Little evidence was available for long-term outcomes (>52 weeks), and RCTs comparing MSCs with therapies other than placebo were lacking. MSC therapy was found to be equally safe but not safer than placebo.