lderitification and analysis of the factors related to the proliferation and differentiation of the adult liver progeritor cells

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Infra present study, we analyzed the factors related to the proliferation and differentiation of the Inter progenitor cells.We obtained the following new findings.1) Ductular reaction (DR) in the liver are thought to be result from progenitor cell proliferation. We analyzed the DR in submassive hepatic necrosis (SHN) in human livers. Cells in DR expressed high level of c-met, NCAM, β-1, α 6 integrin, These cells also specifically expressed CD133 and DLK. DR always resided in a laminin rich matrix and closely contacted with o SMA positive cells. The area in which the cell differentiated toward hepatocytes contained high level of TGF a and TGF β 1 and the cell differentiated toward hepatocytes strongly expressed these receptors. These results indicated microenvironment determine the fate of progenitor cell differentiation.2) The roles of bone marrow cells (BMCs) in hepatic regeneration and carcinogenesis are still unknown. We analyzed whether oval cells are derived from BMCs and whether preneoplastic nodules or HCCs originate from BMCs in the choline-deficient, ethionine-supplemented (CDE) diet rat model. To clarify the origin of constituent cells in the liver, we transplanted BMCs from green fluorescent protein (GFP)-transgenic female rats into male rats, which were then exposed to a CDE diet to induce hepatocarcinogenesis. Some oval cells showed both donor-derived GFP expression and the recipient-specific Y chromosome, indicating that donor BMCs fused with recipient oval cells. Several preneoplastic nodules (precancerous lesions) were induced by CDE treatment. However, these preneoplastic nodules were not GFP-positive. In conclusion, this study has produced two major findings. First, BMCs fuse with some oval cells. Second, BMC-fused oval cells and BMCs might not have malignant potential in the CDE-treated rat model.