Durable Response in Patients With Refractory Fistulizing Perianal Crohn’s Disease Using Autologous Mesenchymal Stem Cells on a Dissolvable Matrix: Results from the Phase I Stem Cell on Matrix Plug Trial

BACKGROUND: Refractory perianal Crohn’s disease remains notoriously difficult to treat. We developed a novel technology using a commercially available bioabsorbable fistula plug to deliver autologous adipose derived mesenchymal stem cells. OBJECTIVE: Assess therapeutic safety and feasibility in the completed STOMP trial. DESIGN: Prospective single-arm phase I clinical trial. SETTING: Tertiary academic medical center. PATIENTS: Adults (18-65) with complex single tract Crohn’s disease perianal fistula who have failed conventional therapy. INTERVENTION: Autologous adipose derived mesenchymal stem cells were isolated, ex vivo culture-expanded, and seeded onto a commercially available bioabsorbable fistula plug. Six weeks later, patients returned to the operating room for removal of the seton and placement of the stem cell-loaded plug. MAIN OUTCOME MEASURES: Patients were followed for a total of 8 visits through 12 months. Safety was the primary endpoint; clinical healing and MRI response were secondary endpoints. RESULTS: Twenty patients (12 female, mean age 36 years) were treated with the stem cell-loaded plug. Of the 20 patients enrolled, three were not included in the 12 month analysis due to study withdrawal. Through 12 months, no patient experienced a serious adverse event related to the stem cell-loaded plug. Four patients experienced 7 serious adverse events and 12 patients experienced 22 adverse events. Complete clinical healing occurred in 14 of 18 patients at 6 months and 13 of 17 patients at 12 months. MRI response was observed in 12 of 18 patients at 6 months. LIMITATIONS: The main limitations are the small sample size and restrictive inclusion criteria. CONCLUSIONS: A stem cell-loaded plug can safely and effectively deliver cell-based therapy for patients with single tract fistulizing perianal Crohn’s disease. See Video Abstract at http://links.lww.com/DCR/C70.