Development of intestinal organoids and microphysiological systems and their application to drug discovery

Abstract

The intestines are an important organ with a variety of functions. For drug discovery research, experimental animals and Caco-2 cells derived from a human colon carcinoma may be used to evaluate the absorption and safety of orally administered drugs. These systems have issues, such as species differences with humans in experimental animals, variations in gene expression patterns, very low drug-metabolizing activities in Caco-2 cells, and the recent trend toward reduced animal testing. Thus, there is a need for new evaluation systems. Intestinal organoid technology and microphysiological systems (MPS) have attracted attention as novel evaluation systems for predicting drug disposition, safety, and efficacy in humans in vitro. Intestinal organoids are three-dimensional structures that contain a variety of intestinal cells. They also contain crypt-villus structures similar to those of living bodies. Using MPS, it is possible to improve the functionality of cells and evaluate the linkage and crosstalk between the intestine and the liver. These systems are expected to be powerful tools for drug discovery research to predict efficacy and toxicity in humans. This review outlines the current status of intestinal organoids and MPS studies.

Keywords: Drug discovery; Induced pluripotent stem cell; Intestinal organoid; Microphysiological system; Primary enterocyte.