Reproduction in vitro d'un intestin sur puce microfluidique
Abstract
The epithelium of the small intestine is composed of a single layer of epithelial cells lining the villi that project into the lumen of the gut, and the crypts that descend into the underlying connective tissue. Dividing stem cells are contained within the crypts and give rise to five types of specialized epithelial cells including enterocytes, Goblet cells, Paneth cells, enteroendocrine cells and Tuft cells. Most of those cells travel upwards from the crypt towards the villus tip where they shed into the lumen except for Paneth cells that remain confined into the crypt. The basement membrane underlines the basal surface of epithelium and separates it from the stroma mostly composed of collagen I and fibroblasts. The whole intestinal epithelium is renewed every week. Many biochemical pathways that control intestinal homeostasis are discovered using mouse models. In contrast, in vitro models systems, such as organoids, provide a mean to investigate questions hard to be addressed in vivo. Despite their obvious interest, organoids do not fully recapitulate intestinal features: the total number of cells does not remain constant, villi-like structures are missing as well as cells and matrix constitutive of the stroma. Only two microfabricated devices have been developed to overcome this absence of villi by replicating dynamic (i.e the peristaltic motion) or structural feature (i.e the topography of the villus) of the intestine in order to induce the formation of villi. However…
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