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Cell Research

Cell Research

IF: 25.9
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Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells and their use for the study of hepatotropic pathogens

Published:25 October 2018 DOI: 10.1038/s41422-018-0103-x PMID: 30361550
Gong-Bo Fu, Wei-Jian Huang, Min Zeng, Xu Zhou, Hong-Ping Wu, Chang-Cheng Liu, Han Wu, Jun Weng, Hong-Dan Zhang, Yong-Chao Cai, Charles Ashton, Min Ding, Dan Tang, Bao-Hua Zhang, Yi Gao, Wei-Feng Yu, Bo Zhai, Zhi-Ying He, Hong-Yang Wang, He-Xin Yan

Abstract

The study of pathophysiological mechanisms in human liver disease has been constrained by the inability to expand primary hepatocytes in vitro while maintaining proliferative capacity and metabolic function. We and others have previously shown that mouse mature hepatocytes can be converted to liver progenitor-like cells in vitro with defined chemical factors. Here we describe a protocol achieving efficient conversion of human primary hepatocytes into liver progenitor-like cells (HepLPCs) through delivery of developmentally relevant cues, including NAD?+?-dependent deacetylase SIRT1 signaling. These HepLPCs could be expanded significantly during in vitro passage. The expanded cells can readily be converted back into metabolically functional hepatocytes in vitro and upon transplantation in vivo. Under three-dimensional culture conditions, differentiated cells generated from HepLPCs regained the ability to support infection or reactivation of hepatitis B virus (HBV). Our work demonstrates the utility of the conversion between hepatocyte and liver progenitor-like cells for studying HBV biology and antiviral therapies. These findings will facilitate the study of liver diseases and regenerative medicine.

Substances (14)

Materials
Procduct Name CAS Molecular Formula Supplier Price
CHIR-99021 252917-06-9 C22H18Cl2N8 340 suppliers $28.00-$4401.00
CHIR-99021 252917-06-9 C22H18Cl2N8 340 suppliers $28.00-$4401.00
CHIR-99021 252917-06-9 C22H18Cl2N8 340 suppliers $28.00-$4401.00
CHIR-99021 252917-06-9 C22H18Cl2N8 340 suppliers $28.00-$4401.00
Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O 226 suppliers $23.00-$5472.00
Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O 226 suppliers $23.00-$5472.00
Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O 226 suppliers $23.00-$5472.00
Y27632 (hydrochloride) 129830-38-2 C14H23Cl2N3O 226 suppliers $23.00-$5472.00
A-83-01 909910-43-6 C25H19N5S 168 suppliers $10.00-$3420.00
A-83-01 909910-43-6 C25H19N5S 168 suppliers $10.00-$3420.00

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