Origin and characterization of a human bipotent liver progenitor cell line
Origin and characterization of a human bipotent liver progenitor cell line
复制标题
DOI：
10.1053/j.gastro.2004.01.002
复制
发表时间：
2004-04-01
期刊：
影响因子：
29.4
通讯作者：
Petit, MA
中科院分区：
文献类型：
--
作者：
Parent, R;Marion, MJ;Petit, MA
背景与目的：肝祖细胞可能在人类慢性肝病的癌变过程中起重要作用。HepaRG细胞系已从与慢性丙型肝炎相关的肝肿瘤中建立。我们观察到，这些细胞表现出明显的形态异质性，显示肝细胞样和胆汁样上皮表型。我们的目标是确定它们是否可以与肝脏祖细胞共享一些特征。方法：采用免疫荧光、免疫印迹和流式细胞术在不同培养阶段进行表型研究。结果：HepaRG细胞在特定条件下逐渐表现出极化和功能性肝细胞和胆管样细胞特征。然而，细胞角蛋白18和19的共表达，观察所有沿着的成熟过程与卵圆细胞特异性标志物（M2-PK，OV-1，OV-6，和CD 34）;动力学和表达谱依赖于细胞群体。此外，在表皮生长因子的存在下，可以观察到对肝细胞谱系的强烈承诺。纤维化肝脏的免疫组织化学显示HepaRG细胞起源的非典型小管反应，显示出特异性限于胆汁肿瘤的可比免疫表型。结论：HepaRG细胞构成了第一个描述的人肝双能祖细胞系的表型和组织学起源。
Background & Aims: Liver progenitor cells may be important in carcinogenesis resulting from human chronic liver diseases. The HepaRG cell line has been established from a liver tumor associated with chronic hepatitis C. We observed that these cells showed an evident morphological heterogeneity, displaying both hepatocyte-like and biliary-like epithelial phenotypes. Our goal was to determine whether they could share some features with liver progenitor cells. Methods: Phenotypic studies using immunofluorescence, immunoblotting, and flow cytometry were performed at different culture stages. Results: HepaRG cells progressively exhibited polarized and functional hepatocytes and bile duct-like cell features under defined conditions. Cytokeratin 18 and 19 coexpression was, however, observed all along the maturation process together with oval cell-specific markers (M2-PK, OV-1, OV-6, and CD34); kinetics and expression profiles were dependent on the cell population. In addition, a strong commitment toward the hepatocytic lineage could be observed in the presence of epidermal growth factor. Immunohistochemistry on the fibrotic liver showing the atypical ductular reaction from which HepaRG cells originated displayed a comparable immunophenotype specifically restricted to bile neoductules. Conclusions: HepaRG cells constitute the first described human hepatic bipotent progenitor cell line regarding phenotype and histological origin.