Journal
EXPERIMENTAL CELL RESEARCH
Volume 341, Issue 2, Pages 207-217Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2016.02.006
Keywords
Extracellular matrix; Acellular matrix; Human embryonic stem cell; Human induced pluripotent stem cell; Hepatic differentiation; HepaRG
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Funding
- EU-FP7 (LIV-ES Project) [HEALTH-F5-2008-223317]
- Academy of Finland [259990, 294193, 294194]
- Tekes-The Finnish Funding Agency for Technology and Innovation [40206/08, 40050/09]
- Doctoral Programme in Materials Research and Nanosciences
- National Doctoral Programme in Nanoscience
- Academy of Finland (AKA) [259990, 294193, 294194, 294194, 294193, 259990] Funding Source: Academy of Finland (AKA)
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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. (C) 2016 Elsevier Inc. All rights reserved.
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