| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Research Abstract |
We transfected adenovirus-mediated HNF-4 into hepatic progenitor cells, and analyzed the expressions of the liver-specific functions. Adenovirus-mediated HNF-4 gene transfer resulted in increases in the expressions of HNF-4, apolipoprotein (Apo) A1 ApoC3, and pregnane X receptor (PXR) mRNA. HNF-4-overexpressing hepatic progenitor cells were then injected into recipient mice, which were treated with dimethylnitrosamine and 30% partial hepatectomy. The treated mice survived significantly longer than the control mice. 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. Male Wistar rats were administered 2-acetylaminofluorene subcutaneously. Seven days later, they received 70% partial hepatectomy and infected with a recombinant adenovirus carrying the cDNA for HNF-4 or Lac-Z. The total numbers of oval cells significantly decreased in the HNF-4 treated rats. At this point, HNF-4-treated rats experienced an inhibition of liver cell proliferation, while mRNA expressions of HNF-4, apolipoprotein CIII, tyrosine amino transferase and albumin, markers for the differentiation of hepatocytes, increased. In contrast, mRNA expression of cytokeratin-19, a marker for the differentiation of biliary epithelial cells, decreased in the livers of HNF-4 transferred rats. These findings demonstrate that adenovirus-mediated HNF-4 transfection induces the differentiation from hepatic progenitor cells to hepatic parenchymal cells in vitro and that these cells may be useful as a source for cell transplantation in liver diseases. The transfer of HNF-4 gene could accelerate the differentiation of hepatic oval cells to hepatocytes.
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