RRC ID 11934
Author Haque A, Hexig B, Meng Q, Hossain S, Nagaoka M, Akaike T.
Title The effect of recombinant E-cadherin substratum on the differentiation of endoderm-derived hepatocyte-like cells from embryonic stem cells.
Journal Biomaterials
Abstract Generation of specific lineages of cells from embryonic stem (ES) cells is pre-requisite to use these cells in pre-clinical applications. Here, we developed a recombinant E-cadherin substratum for generation of hepatic progenitor populations at single cell level. This artificial acellular feeder layer supports the stepwise differentiation of ES cells to cells with characteristics of definitive endoderm, hepatic progenitor cells, and finally cells with phenotypic and functional characteristics of hepatocytes. The efficient differentiation of hepatic endoderm cells (approximately 55%) together with the absence of neuroectoderm and mesoderm markers suggests the selective induction of endoderm differentiation. The co-expression of E-cahderin and alpha-fetoprotein (approximately 98%) suggests the important role of E-cadherin as a surface marker for the enrichment of hepatic progenitor cells. With extensive expansion, approximately 92% albumin expressing cells can be achieved without any enzymatic stress and cell sorting. Furthermore, these mouse ES cell-derived hepatocyte-like cells showed higher morphological similarities to primary hepatocytes. In conclusion, we demonstrated that E-cadherin substratum can guide differentiation of ES cells into endoderm-derived hepatocyte-like cells. This recombinant extracellular matrix could be effectively used as an in vitro model for studying the mechanisms of early stages of liver development even at single cell level.
Volume 32(8)
Pages 2032-42
Published 2011-3-1
DOI 10.1016/j.biomaterials.2010.11.045
PII S0142-9612(10)01484-5
PMID 21163520
MeSH Activins / metabolism Animals Biomarkers / metabolism Cadherins / genetics Cadherins / metabolism* Cell Culture Techniques Cell Differentiation / physiology* Cell Lineage Cells, Cultured Embryonic Stem Cells / cytology Embryonic Stem Cells / physiology* Endoderm / cytology* Endoderm / physiology Extracellular Matrix / chemistry* Gene Expression Regulation Hepatocytes / cytology Hepatocytes / physiology* Male Materials Testing Mice Recombinant Proteins / genetics Recombinant Proteins / metabolism*
IF 10.273
Times Cited 31
DNA material Mouse E-cadherin full length cDNA Mouse E-cadherin cDNA (RDB01184)