Generation of functionally competent hepatic stellate cells from human stem cells to model liver fibrosis in vitro

• DOI: 10.1016/j.stemcr.2022.09.010
• Publication Date: 2022-10-20T14:59:26Z
• Authors: Xinyuan Lai; Chuanyun Li; Chengang Xiang; Zihang Pan; Kai Zhang; Lei Wang; Bingqing Xie; Junning Cao; Jihang Shi; Juan Deng; Shichun Lu; Hongkui Deng; Hui Zhuang; Tong Li; Yan Shi; Kuanhui Xiang
• Keywords: Hepatic stellate cell; Thioacetamide

The detailed understanding of fibrogenesis has been hampered by a lack important functional quiescence characteristics and an in vitro model to recapitulate hepatic stellate cell (HSC) activation. In our study, we establish robust endoderm- mesoderm-sourced quiescent-like induced HSCs (iHSCs) derived from human pluripotent stem cells. Notably, iHSCs present features mature HSCs, including accumulation vitamin A the lipid droplets maintained quiescent features. addition, display fibrogenic response secrete collagen I hepatoxicity caused thioacetamide, acetaminophen, hepatitis B C virus infection. Antiviral therapy attenuated virally iHSC Interestingly, mesoderm-derived showed similar phenotypes. Therefore, provide novel method efficiently generate hESC iPSC differentiation, which could be used as for hepatocyte toxicity prediction, anti-liver-fibrosis drug screening, viral hepatitis-induced liver fibrosis.