Generation of Zone-specific Hepatocyte-like Cells from Human Induced Pluripotent Stem Cells for Accurate Prediction of Drug-induced Hepatotoxicity.

[Generation of Zone-specific Hepatocyte-like Cells from Human Induced Pluripotent Stem Cells for Accurate Prediction of Drug-induced Hepatotoxicity]. Yakugaku Zasshi. 2019;139(12):1509-1512 Authors: Mitani S Abstract Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) are expected to be applicable to large-scale in vitro hepatotoxicity screening systems. Accordingly, methods for generating HLCs from human iPS cells have been improved over the past decade. However, although human hepatocytes have zone-specific characteristics in vivo, there is currently no technique to generate zone-specific HLCs from human iPS cells. Therefore, to generate HLCs with zone-specific properties from human iPS cells, we cultured iPS-HLCs using a parenchymal or nonparenchymal cell-conditioned medium (CM). The results showed that urea production and gluconeogenesis capacity in iPS-HLCs were increased by culturing with cholangiocyte-CM, and glutamine production and drug metabolism capacity in iPS-HLCs were increased by culturing with hepatocyte-CM. It was thus clarified that iPS-HLCs acquire zone 1 hepatocyte-like properties by culturing with cholangiocyte-CM and that iPS-HLCs acquire zone 3 hepatocyte-like properties by culturing with hepatocyte-CM. In addition, we found that WNT inhibitory factor-1 secreted from cholangiocytes, and WNT7B and WNT8B secreted from hepatocytes play important roles in the zone-specific conversion of iPS-HLCs. We hope ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research

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