[Generation of Zone-specific Hepatocyte-like Cells from Human Induced Pluripotent Stem Cells for Accurate Prediction of Drug-induced Hepatotoxicity].
Yakugaku Zasshi
; 139(12): 1509-1512, 2019.
Article
in Ja
| MEDLINE
| ID: mdl-31787637
ABSTRACT
Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) are expected to be applicable to large-scale in vitro hepatotoxicity screening systems. Accordingly, methods for generating HLCs from human iPS cells have been improved over the past decade. However, although human hepatocytes have zone-specific characteristics in vivo, there is currently no technique to generate zone-specific HLCs from human iPS cells. Therefore, to generate HLCs with zone-specific properties from human iPS cells, we cultured iPS-HLCs using a parenchymal or nonparenchymal cell-conditioned medium (CM). The results showed that urea production and gluconeogenesis capacity in iPS-HLCs were increased by culturing with cholangiocyte-CM, and glutamine production and drug metabolism capacity in iPS-HLCs were increased by culturing with hepatocyte-CM. It was thus clarified that iPS-HLCs acquire zone 1 hepatocyte-like properties by culturing with cholangiocyte-CM and that iPS-HLCs acquire zone 3 hepatocyte-like properties by culturing with hepatocyte-CM. In addition, we found that WNT inhibitory factor-1 secreted from cholangiocytes, and WNT7B and WNT8B secreted from hepatocytes play important roles in the zone-specific conversion of iPS-HLCs. We hope that our findings will facilitate the application of iPS-HLCs to drug discovery research.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatocytes
/
Drug Discovery
/
Induced Pluripotent Stem Cells
/
Chemical and Drug Induced Liver Injury
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
Ja
Journal:
Yakugaku Zasshi
Year:
2019
Document type:
Article