Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn’s Disease: Rationale,Clinical Results and Perspectives |
| |
Authors: | Etienne Buscail Guillaume Le Cosquer Fabian Gross Marine Lebrin Laetitia Bugarel Cline Deraison Nathalie Vergnolle Barbara Bournet Cyrielle Gilletta Louis Buscail |
| |
Affiliation: | 1.Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France;2.IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.);3.Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.);4.Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.) |
| |
Abstract: | Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures. |
| |
Keywords: | perianal fistula Crohn’ s disease mesenchymal stem cells adipose-derived stem cells allogenic stem cells |
|
|