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Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes

Authors :
Takeshi Katsuda
Juntaro Matsuzaki
Tomoko Yamaguchi
Yasuhiro Yamada
Marta Prieto-Vila
Kazunori Hosaka
Atsuko Takeuchi
Yoshimasa Saito
Takahiro Ochiya
Source :
eLife, Vol 8 (2019)
Publication Year :
2019
Publisher :
eLife Sciences Publications Ltd, 2019.

Abstract

Hepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into progenitor-like cells with a repopulative capacity using small molecule inhibitors. Here, we demonstrate that hepatic progenitor cells can be obtained from human infant hepatocytes using the same strategy. These cells, named human chemically induced liver progenitors (hCLiPs), had a significant repopulative capacity in injured mouse livers following transplantation. hCLiPs redifferentiated into mature hepatocytes in vitro upon treatment with hepatic maturation-inducing factors. These redifferentiated cells exhibited cytochrome P450 (CYP) enzymatic activities in response to CYP-inducing molecules and these activities were comparable with those in primary human hepatocytes. These findings will facilitate liver cell transplantation therapy and drug discovery studies.

Details

Language :
English
ISSN :
2050084X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.3adfae0cfa1f4d23b2d2a3673219199e
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.47313