Generation of functional ciliated cholangiocytes from human pluripotent stem cells

Mina Ogawa, Jia-Xin Jiang, Sunny Xia, Donghe Yang, Avrilynn Ding, Onofrio Laselva, Marcela Hernandez, Changyi Cui, Yuichiro Higuchi, Hiroshi Suemizu, Craig Dorrell, Markus Grompe, Christine E. Bear and Shinichiro Ogawa ()
Additional contact information
Mina Ogawa: University Health Network
Jia-Xin Jiang: Programme in Molecular Medicine, Research Institute, Hospital for Sick Children
Sunny Xia: Programme in Molecular Medicine, Research Institute, Hospital for Sick Children
Donghe Yang: University Health Network
Avrilynn Ding: University Health Network
Onofrio Laselva: Programme in Molecular Medicine, Research Institute, Hospital for Sick Children
Marcela Hernandez: University Health Network
Changyi Cui: University Health Network
Yuichiro Higuchi: Central Institute for Experimental Animals
Hiroshi Suemizu: Central Institute for Experimental Animals
Craig Dorrell: Oregon Health and Science University
Markus Grompe: Oregon Health and Science University
Christine E. Bear: Programme in Molecular Medicine, Research Institute, Hospital for Sick Children
Shinichiro Ogawa: University Health Network

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract The derivation of mature functional cholangiocytes from human pluripotent stem cells (hPSCs) provides a model for studying the pathogenesis of cholangiopathies and for developing 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 generate functional hPSC-derived cholangiocytes that display many characteristics of mature bile duct cells including high levels of cystic fibrosis transmembrane conductance regulator (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 cystic fibrosis drugs and for studying the role of cilia in cholangiocyte development and function. Transplantation studies show that the mature cholangiocytes generate ductal structures in the liver of immunocompromised mice indicating that it may be possible to develop cell-based therapies to restore bile duct function in patients with biliary disease.

Date: 2021
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DOI: 10.1038/s41467-021-26764-0

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