Intestinal fibrosis is a frequent and harmful complications of Crohn’s disease (CD), resulting in bowel obstruction, repeated bowel resection and short bowel syndrome. CDS is therefore a life-threatening disease. It is estimated that there are 400,000-600,000 patients with CD in North America alone and over one third of these patients have a stenosing disease phenotype. CD is characterized by transluminal, granulomatous inflammation and thickening of the bowel wall due to overgrowth of the muscularis layers and to fibrosis. Although the etiology of CDS is not fully identified, it is clear that excess collagen deposition and mesenchymal cell accumulation contribute to this process.
Most CD patients will require surgery during their lifetime. Approximately 80% of patients exhibit endoscopical restenosis within 1 year after surgery. Given the fact that CD affects young people, the typical CD disease course significantly degrades their QOL. Endoscopic balloon dilatation (EBD) is the currently accepted strategy to prevent repeated surgery, but it is still a challenge to achieve favorable long-term outcomes due to perforation, mucosal bleeding and restenosis over the short term. There is a critical need for additional therapies that prevent or reverse intestinal fibrosis and stenosis, thus promoting the restoration of intestinal integrity.
Several classes of anti-CD drug have recently been developed: anti-TNF-α, anti-α4 integrin, anti-IL6R, anti-IL-12/23, CCR9-inhibitors, to name a few. However, the mechanisms of these drugs focus on the modulation of inflammation, are not necessarily anti-fibrotic. Growing experimental evidence suggests that fibrosis is no longer seen as irreversible and a novel anti-fibrotic drug is expected for CD. Fibroblasts are the effector mesenchymal cells and present in large numbers in the gut system. The degree of the accumulation at tissue level and the activation at cell level of fibroblasts correlates with the appearance of intestinal fibrosis. Therefore, an understanding of in vivo fibroblast-biology is key to successfully develop anti-fibrosis therapeutics for CDS.
