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Functional Activity of Human Hepatoma Cells Transfected With Adenovirus-Mediated Hepatocyte Nuclear Factor (HNF)-4 Gene

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Abstract:

Fulminant hepatic failure (FHF) is still associated with high mortality despite recent advances in medical management. There is need of an effective and safe bioartificial liver (BAL) support to help keep patients with FHF alive until an organ becomes available for transplantation or the native liver recovers. The aim of this study was to establish highly functional liver cells by means of transfecting hepatocyte nuclear factor (HNF)-4 gene for the development of BAL. We constructed adenovirus vector carrying rat HNF-4 cDNA, and transfected to hepatoma-derived cell lines, HepG2 and HuH-7, to enforce expression of the exogenous HNF-4 gene. We analyzed expression of HNF-4, HNF-1, and liver-specific genes in cells infected by the adenovirus vector expressing HNF-4. Adenovirus-mediated HNF-4 gene transfer resulted in increases in expressions of HNF-4, HNF-1, and liver-specific genes such as apolipoproteins, α1-antitrypsin (α1-AT), phosphoenolpyruvate carboxy-kinase, cytochrome P450 families, and glutamine synthetase in transfected hepatoma cells. Cells overexpressing HNF-4 removed ammonia from medium supplemented with NH4Cl to a greater extent than control cells. These findings demonstrated that transfected cell lines restored differentiated gene expressions and liver-specific function by the overproduction of HNF-4. HNF-4-overexpressing hepatocyte cell lines are useful for bioreactor of BAL systems.

Keywords: Adenovirus; Bioartificial liver; Fulminant hepatic failure; Hepatocyte nuclear factor-4; Transcription factor

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000004783983855

Affiliations: 1: *First Department of Internal Medicine, Gifu University School of Medicine, Gifu 501-1194, Japan 2: †Laboratory of Cellular Biochemistry, Siebold University of Nagasaki, Nagayo, Nagasaki 851-2195, Japan 3: ‡Department of Neurology and Psychiatry, Gifu University School of Medicine, Gifu 501-1194, Japan

Publication date: January 1, 2004

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
cog/ct/2004/00000013/00000004/art00009
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