A Phase IB/IIA Study of Ex Vivo Expanded Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells for the Treatment of Perianal Fistulizing Crohn's Disease

BACKGROUND: Mesenchymal stem cells have been used for the treatment of perianal Crohn's fistulizing disease by direct injection. However, no studies to date have included patients with proctitis, anal canal involvement, and multiple branching tracts. OBJECTIVE: This study aimed to determine safety and efficacy of mesenchymal stem cells for refractory perianal Crohn's disease. DESIGN: Phase IB/IIA randomized controlled trial. SETTINGS: Tertiary IBD referral center. PATIENTS: Adult Crohn's disease patients with perianal fistulizing disease. INTERVENTION: Seventy-five million mesenchymal stem cells were administered with a 22-G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million mesenchymal stem cells at 3 months was given if complete clinical and radiographic healing were not achieved. MAIN OUTCOMES MEASURES: Adverse and serious adverse events occurred at postprocedure day 1, week 2, week 6, month 3, month 6, and month 12. Clinical healing, radiographic healing per MRI, and patientreported outcomes were collected at the same time points. RESULTS: A total of 23 patients were enrolled and treated; 18 were treatment patients and 5 were control. There were no adverse or serious adverse events reported related to mesenchymal stem cell therapy. At 6 months, 83% of the treatment group and 40% of the control group had complete clinical and radiographic healing. The perianal Crohn's disease activity index, Wexner incontinence score, and VanAssche score had all significantly decreased in treatment patients at 6 months; none significantly decreased in the control group. LIMITATIONS: Single institution and single blinded. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/C128.