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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
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01274218
Contributor : Laurent Jonchère <>
Submitted on : Monday, February 15, 2016 - 4:03:52 PM
Last modification on : Tuesday, March 10, 2020 - 4:33:58 PM

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Liisa K. Kanninen, Pauliina Porola, Johanna Niklander, Melina M. Malinen, Anne Corlu, et al.. Hepatic differentiation of human pluripotent stem cells on human liver progenitor HepaRG-derived acellular matrix. Experimental Cell Research, Elsevier, 2016, 341 (2), pp.207-217. ⟨10.1016/j.yexcr.2016.02.006⟩. ⟨hal-01274218⟩

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