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Generation of functional ciliated cholangiocytes from human pluripotent stem

ABSTRACT: Generation of functional ciliated cholangiocytes from human pluripotent stem

PROVIDER: PRJNA732650 | ENA |

REPOSITORIES: ENA

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Generation of functional ciliated cholangiocytes from human pluripotent stem

Project description:We report on the successful generation of functional ciliated cholangoocytes from hPSCs that will provide new opportunities to study and treat diseases of the liver. Both monolayer- and organoid-derived cells are adaptable for further bioengineering approcahes to produce more complex hPSC-deived liver tissue with biliary ductal structures. Additionally, the successful engraftment of differentiated cholangiocytes in the liver of immune-imcompetent mice provides the basis for developing novel therapeutic strategies to treat cholangiopathies.

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Project description:The ever-increasing therapeutic and pharmaceutical demand for liver cells calls for systems that enable mass production of hepatic cells. Here we describe a large-scale suspension system that uses human endoderm stem cells (hEnSCs) as precursors to generate functional and transplantable hepatocytes (E-heps) or cholangiocytes (E-chos). hEnSC-derived hepatic populations are characterized by single-cell transcriptomic analyses and compared with hESC-derived counterparts, in-vitro-maintained or -expanded primary hepatocytes and adult cells, which reveals that hepatic differentiation of hEnSCs recapitulates in vivo development and that the heterogeneities of the resultant populations can be manipulated by regulating the EGF and MAPK signaling pathways. Functional assessments demonstrate that E-heps and E-chos possess properties comparable with adult counterparts and that, when transplanted intraperitoneally, encapsulated E-heps were able to rescue rats with acute liver failure. Our study lays the foundation for cell-based therapeutic agents and in vitro applications for liver diseases.

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