Animal models and sources of mesenchymal cells in intestinal fibrosis

Abstract

Intestinal fibrosis is a common complication in patients with Crohn’s disease (CD) that often results in an impaired quality of life of affected patients. In the absence of specific anti-fibrotic medical therapy, patients with stricturing CD often have to undergo invasive endoscopic treatment approaches or surgical intervention. Beside the lack of medical treatment options for stricturing CD, the diagnostic work-up is hampered by the limited accuracy of methods for detection, characterization and grading of intestinal fibrosis. Therefore, functional studies as well as studies evaluating novel diagnostic and therapeutic approaches for stricturing CD are urgently needed and require appropriate animal models as a prerequisite. Over recent years, several animal models for intestinal fibrosis have been established that allow for evaluation of experimental fibrosis at different stages and in the context of different pro-fibrotic triggers. In the following chapter, a variety of animals models will be presented, specific advantages and disadvantages will be emphasized and the overall relevance and applicability of these models to study human fibrostenotic IBD will be discussed. In the second part of the chapter, different sources of mesenchymal cells, one of the key executor of intestinal fibrogenesis, will be discussed. In addition to well known mechanism such as proliferation and migration of fibroblasts, novel aspects such as cellular transdifferentiation including epithelial- and endothelial to mesenchymal transition will be described. Finally, novel techniques to traffic cellular fate will be displayed.