RRC ID 11961
Author Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H.
Title Differentiation of mouse hepatic progenitor cells induced by hepatocyte nuclear factor-4 and cell transplantation in mice with liver fibrosis.
Journal Transplantation
Abstract BACKGROUND:Hepatocyte nuclear factor-4 (HNF-4) plays a central role in the differentiation process of hepatic cells. We investigated the effects of an overexpression of HNF-4 on hepatic progenitor cells isolated from a fetal mouse liver and transplantation of the cells in a mouse model of liver fibrosis.
METHODS:Hepatic progenitor cells were isolated from the embryonic day 14.0 fetal mouse livers and were purified by magnetic cell sorting to remove the hematopoietic cells. We transfected adenovirus-mediated HNF-4 into the cells, and analyzed the expressions of the liver-specific functions using reverse-transcription polymerase chain reaction and Northern blotting. HNF-4-overexpressing hepatic progenitor cells were then injected into recipient mice, which were treated with dimethylnitrosamine and 30% partial hepatectomy.
RESULTS:After 5 days of culture, the cells located in the center of the aggregates were stained positive for albumin, but the peripheral cells for cytokeratin 19. Adenovirus-mediated HNF-4 gene transfer resulted in increases in the expressions of HNF-4, apolipoprotein (Apo)A1, ApoC3, and pregnane X receptor messenger RNA. The mice treated with HNF-4-transfected progenitor cells survived significantly longer than the control mice (P=0.004). The plasma levels of albumin, total cholesterol, and glucose were higher in the mice treated with cells transfected by HNF-4 than in the control mice.
CONCLUSIONS:These findings demonstrate that adenovirus-mediated HNF-4 transfection induces the differentiation from hepatic progenitor cells to hepatic parenchymal cells in vitro. These cells may be useful as a source for cell transplantation in liver diseases.
Volume 86(9)
Pages 1178-86
Published 2008-11-15
DOI 10.1097/TP.0b013e31818a8233
PII 00007890-200811150-00005
PMID 19005397
MeSH Adenoviridae Animals Apolipoprotein A-I / metabolism Apolipoprotein C-III / metabolism Cell Differentiation* Cells, Cultured Dimethylnitrosamine Disease Models, Animal Fetal Stem Cells / cytology* Fetal Stem Cells / metabolism Fetal Stem Cells / transplantation* Gene Transfer Techniques Genetic Therapy Hepatectomy Hepatocyte Nuclear Factor 4 / genetics Hepatocyte Nuclear Factor 4 / metabolism* Hepatocytes / metabolism Hepatocytes / pathology Liver / cytology* Liver Cirrhosis / chemically induced Liver Cirrhosis / metabolism Liver Cirrhosis / therapy* Mice Mice, Inbred C57BL Mice, Transgenic Pregnane X Receptor Receptors, Steroid / metabolism Stem Cell Transplantation* Transfection
IF 4.546
Times Cited 12
DNA material AxCALacZ Adex1CAlacZ (RDB02726)