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Exp Cell Res. 2016 Feb 15;341(2):207-17. doi: 10.1016/j.yexcr.2016.02.006. Epub 2016 Feb 8.

Hepatic differentiation of human pluripotent stem cells on human liver progenitor HepaRG-derived acellular matrix.

Author information

1
Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland.
2
Inserm UMR991, Liver Metabolisms and Cancer, Université de Rennes 1, F-35043 Rennes, France.
3
Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland; School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
4
Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland. Electronic address: yan-ru.lou@helsinki.fi.

Abstract

Human hepatocytes are extensively needed in drug discovery and development. Stem cell-derived hepatocytes are expected to be an improved and continuous model of human liver to study drug candidates. Generation of endoderm-derived hepatocytes from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, is a complex, challenging process requiring specific signals from soluble factors and insoluble matrices at each developmental stage. In this study, we used human liver progenitor HepaRG-derived acellular matrix (ACM) as a hepatic progenitor-specific matrix to induce hepatic commitment of hPSC-derived definitive endoderm (DE) cells. The DE cells showed much better attachment to the HepaRG ACM than other matrices tested and then differentiated towards hepatic cells, which expressed hepatocyte-specific makers. We demonstrate that Matrigel overlay induced hepatocyte phenotype and inhibited biliary epithelial differentiation in two hPSC lines studied. In conclusion, our study demonstrates that the HepaRG ACM, a hepatic progenitor-specific matrix, plays an important role in the hepatic differentiation of hPSCs.

KEYWORDS:

Acellular matrix; Extracellular matrix; HepaRG; Hepatic differentiation; Human embryonic stem cell; Human induced pluripotent stem cell

PMID:
26854693
DOI:
10.1016/j.yexcr.2016.02.006
[Indexed for MEDLINE]

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