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  • Title: Hepatic differentiation of human pluripotent stem cells on human liver progenitor HepaRG-derived acellular matrix.
    Author: Kanninen LK, Porola P, Niklander J, Malinen MM, Corlu A, Guguen-Guillouzo C, Urtti A, Yliperttula ML, Lou YR.
    Journal: Exp Cell Res; 2016 Feb 15; 341(2):207-17. PubMed ID: 26854693.
    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.
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