Differentiation ofhuman iPS cells into hepatocytes and bile duct epithelial cells and application to drug development study

人肝细胞可用于药代动力学检查。然而，相当大的依赖于供体的变异是有问题的。小肠和肝脏在药代动力学的各个方面都扮演着重要的角色。目前，人肠道上皮细胞难以获得，且尚无可鉴赏的模型细胞。取而代之的是，在药物吸收研究中，其他组织细胞来源的细胞系，包括Caco-2细胞和MDCK细胞，被用作肠道模型。人iPS细胞明显分化为各种类型的成熟细胞，因此是常规获取大量细胞的有吸引力的来源，这些细胞可用于替代原代细胞的药代动力学检查。在这项研究中，我们研究了小分子化合物在药代动力学研究中对人iPS细胞分化为肝细胞和空肠细胞的影响。

Human hepatocytes are useful for pharmacokinetic examinations. However, considerable donor-dependent variations are problematic. The small intestine, as well as liver, plays an important role in all aspects of pharmacokinetics. At present, human intestinal epithelial cells are difficult to obtain, and there is no appreciate model cells. Instead, other tissue cell-derived cell lines, including Caco-2 cells and MDCK cells, were used as intestinal model in a drug absorption study. Human iPS cells apparently differentiate into various types of mature cells, and are thereby an attractive source for routine access to large numbers of cells that can be used for the pharmacokinetic examinations replacing primary cells. In this study, we investigated the effects of small-molecule compounds for differentiation of human iPS cells into hepatocytes and enterocytes available in pharmacokinetic study.