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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cell Differentiation / physiology*
  • Endoderm / cytology
  • Hepatocytes / cytology*
  • Human Embryonic Stem Cells / cytology
  • Humans
  • Liver / cytology*
  • Pluripotent Stem Cells / cytology*