Three-dimensional in vitro Gut Model on a Villi-shaped Collagen Scaffold

A three-dimensional (3D) tissue architecture provides essential cellular environmental cues for cell differentiation. We previously reported that Caco-2 human intestinal epithelial cells grown on a 3D villi-shaped scaffold composed of collagen created a tissue structure resembling the human intestinal villi. Here, we compared the absorptive and metabolic properties of Caco-2 cells cultured on the 3D villi with those in 2D monolayer. Cell growth was higher in the 3D villi model compared with the 2D monolayer, probably owing to an increase in the available surface area. Barrier functions were more in vivo-like in the 3D villi model in association with reduced expression of tight junction and transporter proteins. The specific activities of the metabolic enzyme and intestinal epithelial differentiation marker, alkaline phosphatase, were improved in the 3D villi model, whereas aminopeptidase activity was comparable in the two models. These results suggest that the 3D villi scaffold induces physiological changes in Caco-2 cells, related to the absorption and metabolism of drugs. This 3D villi model may serve as an alternative and improved in vitro gut model for studying drug metabolism and transport.