Intestinal cells differentiated from human induced pluripotent stem cells for use in drug development studies

Abstract

In drug development studies, various in vitro model systems (such as Caco-2 cells and intestinal microsomes) are widely used for evaluating intestinal pharmacokinetics and toxicological properties of drugs, including the rate of drug absorption, drug metabolism, and extent of mucosal damage. However, these approaches have limited accuracy in predicting intestinal availability and toxicity. To overcome these problems, new approaches have been recently developed to generate intestinal epithelial cells and organoids that are derived from induced pluripotent stem (iPS) cells, which have shown great potential for use in drug development studies. In this review, we summarized our research regarding intestinal epithelial cells and organoids generated from human iPS cells. We demonstrated that intestinal epithelial cells derived from human iPS cells exhibit drug-metabolizing enzyme activities, drug transporter activities, and cytochrome P450 inducibility. We speculated that drug-induced intestinal mucosal damage in derived epithelial cells can be evaluated. Moreover, intestinal organoids derived from human iPS cells were found to contain various intestinal cell types and develop apical-basal polarity. The differentiated organoids have intestine-like structures with desired pharmacokinetic attributes and barrier functions. Intestinal epithelial cells and organoid tissues derived from human iPS cells show great potential to be more widely used in drug development studies, including pharmacokinetic studies, toxicological evaluations, drug screening, and studies on intestinal bowel disease models.