Document Detail


Generation of hepatocyte-like cells from in vitro transdifferentiated human fetal pancreas.
MedLine Citation:
PMID:  19499706     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although the appearance of hepatic foci in the pancreas has been described in animal experiments and in human pathology, evidence for the conversion of human pancreatic cells to liver cells is still lacking. We therefore investigated the developmental plasticity between human embryonic pancreatic cells and liver cells. Cells were isolated and expanded from 7-8-week-old human fetal pancreata (HFP) and were characterized for the absence and presence of pancreatic and hepatic markers. In vitro expanded HFP were treated with fibroblast growth factor 2 (FGF2) and dexamethasone (DX) to induce a liver phenotye in the cells. These treated cells in various passages were further studied for their capacity to be functional in hepatic parenchyma following retrorsine-induced injury in nude C57 black mice. Amylase- and EPCAM-positive-enriched cells isolated from HFP and treated with FGF2 and DX lost expression of pancreatic markers and gained a liver phenotype. Hepatic differentiation was based on the expression (both at the mRNA and protein level) of liver markers albumin and cytokeratin 19. When transplanted in vivo into nude mice treated with retrorsine, both cell types successfully engrafted and functionally differentiated into hepatic cells expressing human albumin, glycogen, dipeptidyl peptidase, and gamma-glutamyltranspeptidase. These data indicate that human fetal pancreatic cells have a capacity to alter their gene expression profile in response to exogenous treatment with FGF2 and DX. It may be possible to generate an unlimited supply of hepatocytes in vitro for cell therapy.
Authors:
Suchitra Sumitran-Holgersson; Greg Nowak; Shifaan Thowfeequ; Setara Begum; Meghnad Joshi; Marie Jaksch; Anders Kjaeldgaard; Carl Jorns; Bo-Göran Ericzon; David Tosh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell transplantation     Volume:  18     ISSN:  0963-6897     ISO Abbreviation:  Cell Transplant     Publication Date:  2009  
Date Detail:
Created Date:  2009-06-08     Completed Date:  2009-08-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9208854     Medline TA:  Cell Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  183-93     Citation Subset:  IM    
Affiliation:
Division of Transplantation Surgery, Karolinska University Hospital-Huddinge, Karolinska Institutet, Stockholm, Sweden. suchitra.holgersson@surgery.gu.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Differentiation / metabolism
Cell Differentiation*
Cell Transplantation
Cells, Cultured
Dexamethasone / pharmacology
Drug-Induced Liver Injury / etiology,  pathology,  therapy
Female
Fetus / cytology*,  metabolism
Fibroblast Growth Factor 2 / pharmacology
Hepatocytes / cytology*,  metabolism
Humans
Mice
Mice, Nude
Pancreas / cytology*,  metabolism
Pyrrolizidine Alkaloids
Grant Support
ID/Acronym/Agency:
K2005-06X-14004-02B//Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Antigens, Differentiation; 0/Pyrrolizidine Alkaloids; 103107-01-3/Fibroblast Growth Factor 2; 480-54-6/retrorsine; 50-02-2/Dexamethasone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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