title: Hepatic differentiation of human pluripotent stem cells on human liver progenitor HepaRG-derived acellular matrix.
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.
authors: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland.
authors: Liisa K
authors: LK
authors: Kanninen
authors: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland.
authors: Pauliina
authors: P
authors: Porola
authors: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland.
authors: Johanna
authors: J
authors: Niklander
authors: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland.
authors: Melina M
authors: MM
authors: Malinen
authors: Inserm UMR991, Liver Metabolisms and Cancer, Université de Rennes 1, F-35043 Rennes, France.
authors: Anne
authors: A
authors: Corlu
authors: Inserm UMR991, Liver Metabolisms and Cancer, Université de Rennes 1, F-35043 Rennes, France.
authors: Christiane
authors: C
authors: Guguen-Guillouzo
authors: 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.
authors: Arto
authors: A
authors: Urtti
authors: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland.
authors: Marjo L
authors: ML
authors: Yliperttula
authors: 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.
authors: Yan-Ru
authors: YR
authors: Lou
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D004707:Endoderm / Q000166:cytology; D022781:Hepatocytes / Q000166:cytology*; D000066449:Human Embryonic Stem Cells / Q000166:cytology; D006801:Humans; D008099:Liver / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*
keywords: Acellular matrix; Extracellular matrix; HepaRG; Hepatic differentiation; Human embryonic stem cell; Human induced pluripotent stem cell