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.
Highlights
Crohn’s disease (CD) is a chronic inflammatory disease, characterized by idiopathic transmural inflammation anywhere along the gastrointestinal tract [1]
There are still several issues to be resolved in this field: what is the exact mechanism of action of the adipose-derived stem/stromal cells (ADSCs)? What is the best administration protocol in terms of number of cells, timing after drainage and systemic biotherapy, and associated procedures? What is the exact risk of a potential allogenic process?
Of the various tissues studied, many teams have focused on adipose tissue because it is easy to collect in large quantities by liposuction
Summary
Crohn’s disease (CD) is a chronic inflammatory disease, characterized by idiopathic transmural inflammation anywhere along the gastrointestinal tract [1]. Anal and perianal localizations in CD are frequent and the evolution vary from regression to a prolonged and chronic state In this latter case the lesions can worsen with large mucocutaneous and muscular involvement that considerably modify the anorectal architecture [3,4,5,6,7]. The remaining 25% of patients require repeated procedures which carry a high risk of destructive lesions and functional consequences (risk of incontinence) as well as severe alterations in quality of life [18,19] In this context, there is room for other procedures such as biological glue, biological collagen or in situ injection of autologous or allogenic mesenchymal stem cells (MSC) from bone marrow (BM-MSC) or adipose tissue (adipose-derived stem/stromal cells—ADSC). The aim of the present work is to review the relevant properties and the application of ADSCs in the treatment of fistulizing perianal CD, including published and ongoing clinical trials
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