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


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

SUBMITTER: Lai X 

PROVIDER: S-EPMC9669405 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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

Lai Xinyuan X   Li Chuanyun C   Xiang Chengang C   Pan Zihang Z   Zhang Kai K   Wang Lei L   Xie Bingqing B   Cao Junning J   Shi Jihang J   Deng Juan J   Lu Shichun S   Deng Hongkui H   Zhuang Hui H   Li Tong T   Shi Yan Y   Xiang Kuanhui K  

Stem cell reports 20221020 11


The detailed understanding of fibrogenesis has been hampered by a lack of important functional quiescence characteristics and an in vitro model to recapitulate hepatic stellate cell (HSC) activation. In our study, we establish robust endoderm- and mesoderm-sourced quiescent-like induced HSCs (iHSCs) derived from human pluripotent stem cells. Notably, iHSCs present features of mature HSCs, including accumulation of vitamin A in the lipid droplets and maintained quiescent features. In addition, iH  ...[more]

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