Human pluripotent stem cell-derived intestinal epithelial cells maintain small intestine-specific functions over time, even with repeated cell division

The human colon cancer-derived cell line Caco-2 is widely used in drug discovery due to its barrier function and transporter activity. However, Caco-2 cells have extremely low drug metabolic capacity, resulting in discrepancies with human physiology. In this study, we conducted experiments on human intestinal epithelial cells generated from pluripotent stem cell-derived organoids. We assessed cell morphology, gene expression, barrier and transporter functions, drug metabolic capacity, and cytotoxicity in relation to cell growth and the effects of cellular aging. The results indicate that organoid-derived intestinal epithelial cells may be helpful as a new model cell for drug discovery. Understanding the advantages of drug metabolic capacity and cytotoxicity among cryopreserved human enterocytes, the human colon cancer-derived cell line Caco-2, and human pluripotent stem cell-derived intestinal epithelial cells within microphysiological systems and organ-on-chip technologies is essential for the development of an appropriate model system for the small intestine.