Crypt Organoids Culture as an In Vitro Model in Studying Regulation of Xenobiotic Metabolism and drug-induced Cytotoxicity

The gastrointestinal (GI) tract is the largest absorption organ in the body and is also enriched with many of the Xenobiotic Processing Genes (XPGs), which play an important role in xenobiotic bioactivation, metabolism, and detoxification. The application of genetically modified mouse models to study drug metabolism and toxicity has proven beneficial over the past decade, and with the ability to culture primary cells from these animal experiments can now be developed in vitro to examine mechanistic properties. Intestinal stem cells (ISCs), located in the crypt zone at the bottom of the villi, produce and differentiate into intestinal epithelial cells (IECs) as a supply for continuous intestinal renewal. Methods have been established in long-term culture conditions in which one single Lgr5+ stem cell embedded in matrix gel can independently generate villus-like epithelial domains with the presence of all differentiated IECs. Here, we report the application of 3D crypt organoid cultures as a tool for the st...