Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies

Abstract

Summary: The small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiPS-SIECs), which could be applied to drug absorption and metabolism studies. The small intestinal epithelial-like cells were efficiently generated from human induced pluripotent stem cell by treatment with WNT3A, R-spondin 3, Noggin, EGF, IGF-1, SB202190, and dexamethasone. The gene expression levels of small intestinal epithelial cell (SIEC) markers were similar between the hiPS-SIECs and human adult small intestine. Importantly, the gene expression levels of colonic epithelial cell markers in the hiPS-SIECs were much lower than those in human adult colon. The hiPS-SIECs generated by our protocol exerted various SIEC functions. In conclusion, the hiPS-SIECs can be utilized for evaluation of drug absorption and metabolism. : Takayama, Mizuguchi and colleagues have developed a highly efficient small intestinal epithelial cell differentiation protocol from human induced pluripotent stem cells (iPSCs). The human iPSC-derived small intestinal epithelial-like cells (hiPS-SIECs) showed drug absorption and metabolism capacities. Their technology should be useful in the evaluation of pharmacokinetics of oral drugs. Key words: human iPSCs, intestinal epithelial-like cells, drug metabolism, drug absorption