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bioRxiv · 10.1101/2021.03.23.436530

Generation of functional ciliates cholangiocytes from human pluripotent stem cells

Ogawa, M.·Jiang, J.-X.·Xia, S.·Yang, D.·Ding, A.·Laselva, O.·Chin, S.·Hernandez, M.·Cui, C.·Higuchi, Y.·Suemizu, H.·Dorrell, C.·Grompe, M.·Bear, C.·Keller, G.·Ogawa, S.
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Abstract

The derivation of mature functional cholangiocytes from human pluripotent stem cells (hPSCs) would provide a model for studying the pathogenesis of cholangiopathies and for developing novel therapies to treat them. Current differentiation protocols are not efficient and give rise to cholangiocytes that are not fully mature, limiting their therapeutic applications. Here, we describe a new strategy to generate functional hPSC-derived cholangiocytes that display many characteristics of mature bile duct cells including high levels of CFTR and the presence of primary cilia capable of sensing flow. With this level of maturation, these cholangiocytes are amenable for testing the efficacy of new cystic fibrosis drugs and for studying the role of cilia in cholangiocyte development and function. Transplantation studies showed that the mature cholangiocytes generate ductal structures in the liver of immunocompromised mice providing the first indication that it may be possible to develop cell-based therapies to restore bile duct function in patients with biliary disease.

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Ogawa, M., Jiang, J.-X., Xia, S., Yang, D., Ding, A., Laselva, O., Chin, S., Hernandez, M., Cui, C., Higuchi, Y., Suemizu, H., Dorrell, C., Grompe, M., Bear, C., Keller, G., Ogawa, S.. 2021-03-23. Generation of functional ciliates cholangiocytes from human pluripotent stem cells. https://doi.org/10.1101/2021.03.23.436530

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