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

在本研究中，我们分析了影响间祖细胞增殖和分化的相关因素。我们获得了以下新发现。1)肝内的导管反应（DR）被认为是祖细胞增殖的结果。我们分析了人肝脏亚块状肝坏死（SHN）的DR。DR细胞高水平表达c-met、NCAM、β-1、α 6整合素，这些细胞还特异性表达CD133和DLK。DR总是驻留在富含层粘连蛋白的基质中，并与SMA阳性细胞密切接触。细胞向肝细胞分化的区域含有高水平的TGF a和TGF β 1，向肝细胞分化的细胞强烈表达这些受体。这些结果表明微环境决定了祖细胞分化的命运。2)骨髓细胞（BMCs）在肝再生和癌变中的作用尚不清楚。我们分析了胆碱缺乏、补充乙硫氨酸（CDE）的饮食大鼠模型中卵形细胞是否来源于BMCs，以及瘤前结节或hcc是否来源于BMCs。为了阐明肝脏中组成细胞的来源，我们将绿色荧光蛋白（GFP）转基因雌性大鼠的bmc移植到雄性大鼠体内，然后将其暴露于CDE饮食中诱导肝癌发生。一些卵形细胞显示供体来源的GFP表达和受体特异性的Y染色体，表明供体骨髓细胞与受体卵形细胞融合。CDE治疗诱导了几个肿瘤前结节（癌前病变）。然而，这些瘤前结节并非gfp阳性。总之，这项研究产生了两个主要发现。首先，bmc与一些卵形细胞融合。其次，在cde处理的大鼠模型中，bmmc融合的卵形细胞和bmmc可能没有恶性潜能。

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.