| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
We have reported that glomerular mesangial cells in kidney and microglial cells and perivascular-pericyte-like cells in infracted brain are derived from hematopoietic stem cells (HSCs) using chimeric mice generated by transplantation of single enhanced green fluorescent protein (EGFP) -marked lineage negative (Lin^-) Sca-1^+ c-kit^+ CD34^- cells (single cell transplanted mice). It has been reported that oval cells in the liver may differentiate into several lineages including hepatocytes, biliary cells, endocrine and exocrine pancreatic cells, and intestinal epithelial cells. Moreover, oval cells express CD34, Thy-1, c-kit and flt-3 receptor, all of which are also found in HSCs. From these findings, we hypothesized that endocrine pancreatic cells are of HSC origin. To test this hypothesis, we established chronic liver injury model in transplanted mice induced by carbon tetrachloride (CCl4) ; CCl4 was injected into single cell transplanted mice intraperitoneally twice a week for 3 months. We examined the presence of oval cells in the liver and found a lot of EGFP^+ cells in injured liver especially in sinusoid. However, these cells were not oval cells. We tried to clarify the nature of these EGFP^+ cells using the indirect immunofluorescence method. Majority of EGFP^+ cells were negative for CD45 antigen and some cells were stained with oil-red O. Moreover, some other cells were positive for α-smooth muscle actin and glial fibrillary acidic protein. These findings suggest that the phenotype of EGFP^+ cells is consistent with that of hepatic stellate cells and that hepatic stellate cells might be from HSCs. Because hepatic stellate cells play an important role in pathogenesis of liver fibrosis, portal hypertension and fulminant hepatitis, we expect that the results from our examination can contribute to make new treatment strategies for these disorders.
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