A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation

PURPOSE: The effective management of fistulas in patients with Crohn's disease presents an extremely challenging problem. Mesenchymal adult stem cells extracted from certain tissues, such as adipose tissue, can differentiate into various cell types. Therefore, we have tried to use such cells to stimulate heating of Crohn's fistulas. METHODS: We designed a prospective Phase I clinical trial, involving five patients with Crohn's disease, to test the feasibility and safety of autologous stem cells transplantation in the treatment of fistulas. We also studied the expression of various cell markers and the growth rates of the lipoaspirate-derived cells that were used for transplantation. RESULTS: One patient was excluded because of bacterial contamination of cultured cells. We inoculated nine fistulas in four patients with autologous adipose tissue-derived stem cells at Passage 3 or earlier. Eight inoculated fistulas were followed weekly for at least eight weeks. In six fistulas, the external opening was covered with epithelium at the end of Week 8, and, thus, these fistulas were considered healed (75 percent). In the other two fistulas, there was only incomplete closure of the external opening, with a decrease in output flow (not healed; 25 percent). No adverse effects were observed in any patient at the end of the follow-up period (minimum follow-up, 12 months; maximum follow-up, 30 months; follow-up average, 22 months). CONCLUSIONS: To our knowledge, this is the first report of a clinical trial of cell therapy using autologous stem cells obtained from a lipoaspirate. Our results indicate that our protocol is feasible and safe for the treatment of fistulas in Crohn's disease. The number of patients included and the uncontrolled nature of Phase I clinical trials do not allow demonstration of the effectiveness of the treatment. However, the results of the present study encourage to perform further studies in Phase II.