Treatment of Crohn's-Related Rectovaginal Fistula With Allogeneic Expanded-Adipose Derived Stem Cells: A Phase I-IIa Clinical Trial

Abstract

The aim of this clinical trial was to determine the safety and feasibility of expanded allogeneic adiposederived stem cells to treat Crohn¿s-related rectovaginal fistula (CRRVF). We designed a phase I¿II clinical trial (https://ClinicalTrials.gov,NCT00999115)to treat10patientswithCRRVF.Patients receivingbiological therapy during follow-upwere excluded. Curettage was performed, and a vaginal or rectal flap was added if the surgeon considered it necessary. The therapeutic protocol included intralesional injection of 20million stem cells in the vaginal walls (submucosal area) and fistula tract. Healing was evaluated 12 weeks later. If the fistula had not healed, a second dose of 40million stem cells was administered. Patient follow-up was 52weeks from last cell injection. Healingwas defined as re-epithelialization of both vaginal and rectal sides and absence of vaginal drainage. Cytokines and immunological blood testsweremonitored. Serious adverse events or rejection issues were not observed. Five patients were excluded because biologicdrugs wererequired totreat a Crohn¿s disease flare-up during follow-up. Cytokine profiles andimmunotoxicity assays showed no statistically significant alterations. Sixty percent of the nonexcluded patients achievedacompletehealing.Expandedallogeneicadipose-derivedstem-cell injection isasafeandfeasible therapy for treating CRRVF, and the healing success rate seems promising (60%). The results of this trial encourage further exploration into this therapy.