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Human Pluripotent Stem Cell-Derived Organoids as a Model of Intestinal Xenobiotic Metabolism
Kengo Sasaki, Makoto Inoue, Masakazu Machida, Tomoyuki Kawasaki, Satoru Tsuruta, Hajime Uchida, Seisuke Sakamoto, Mureo Kasahara, Akihiro Umezawa, and Hidenori Akutsu
The human intestine is the site of absorption and first-pass metabolism for oral intake. Assessment of absorption, distribution, metabolism, excretion, and toxicity of xenobiotics has transformed the understanding of in vivo pharmacology. However, these processes are difficult to recapitulate in vitro. In this study, a simple protocol was developed for the generation of mature functional intestinal organoids from human pluripotent stem cells under xenogeneic-free conditions. The team sought to characterize transcription level in drug transporters and metabolism and evaluate CYP3A4 catalytic function of the organoids. This model provides a novel platform for pharmacological testing.