Susceptibility of chimeric mice with livers repopulated by serially subcultured human hepatocytes to hepatitis B virus
Susceptibility of chimeric mice with livers repopulated by serially subcultured human hepatocytes to hepatitis B virus
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连续传代培养人肝细胞肝脏嵌合小鼠对乙型肝炎病毒的敏感性
DOI：
10.1002/hep.22057
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发表时间：
2007
期刊：
影响因子：
13.5
通讯作者：
K. Yoshizato
中科院分区：
文献类型：
--
作者：
R. Utoh;C. Tateno;C. Yamasaki;N. Hiraga;M. Kataoka;T. Shimada;K. Chayama;K. Yoshizato
我们之前在成人实质肝细胞（PH）的长期培养物中以 0.01%‐0.09% 的频率识别出一小群复制性肝细胞。这些肝细胞能够通过连续传代培养作为集落形成实质肝细胞（CFPH）持续生长。在本研究中，我们生成了培养的 CFPH 的基因表达谱，发现它们表达细胞角蛋白 19、CD90 (Thy-1) 和 CD44，但不表达成熟肝细胞标记物，如色氨酸-2,3-双加氧酶 (TO) 和葡萄糖-6-磷酸酶 (G6P)，证实这些细胞是肝祖样细胞。培养的 CFPH 对人类乙型肝炎病毒 (HBV) 感染具有抵抗力。为了检查体内细胞的生长和分化能力，将连续传代培养的 CFPH 移植到白蛋白启动子/增强子驱动的尿激酶纤溶酶原激活剂转基因小鼠和严重联合免疫缺陷 (SCID) 小鼠杂交的后代中。这些细胞被植入肝脏并能够生长至少 10 周，最终达到 27% 的最大占用率。宿主肝脏中的CFPH表达分化标记物，例如TO、G6P和细胞色素P450亚型，并且可能感染HBV。具有相对较高替代率的 CFPH 嵌合小鼠表现出病毒血症，并且血清乙型肝炎表面抗原水平较高。结论：连续传代培养的来自出生后肝脏的人肝祖样细胞成功地重新填充了受损的肝脏，并表现出成熟肝细胞的多种表型，包括对 HBV 的易感性。体外扩增的 CFPH 可用于表征人肝祖样细胞的分化状态。 （肝病学 2008 年。）
We previously identified a small population of replicative hepatocytes in long‐term cultures of human adult parenchymal hepatocytes (PHs) at a frequency of 0.01%‐0.09%. These hepatocytes were able to grow continuously through serial subcultures as colony‐forming parenchymal hepatocytes (CFPHs). In the present study, we generated gene expression profiles for cultured CFPHs and found that they expressed cytokeratin 19, CD90 (Thy‐1), and CD44, but not mature hepatocyte markers such as tryptophan‐2,3‐dioxygenase (TO) and glucose‐6‐phosphatase (G6P), confirming that these cells are hepatic progenitor‐like cells. The cultured CFPHs were resistant to infection with human hepatitis B virus (HBV). To examine the growth and differentiation capacity of the cells in vivo, serially subcultured CFPHs were transplanted into the progeny of a cross between albumin promoter/enhancer‐driven urokinase plasminogen activator‐transgenic mice and severe combined immunodeficient (SCID) mice. The cells were engrafted into the liver and were able to grow for at least 10 weeks, ultimately reaching a maximum occupancy rate of 27%. The CFPHs in the host liver expressed differentiation markers such as TO, G6P, and cytochrome P450 subtypes and could be infected with HBV. CFPH‐chimeric mice with a relatively high replacement rate exhibited viremia and had high serum levels of hepatitis B surface antigen. Conclusion: Serially subcultured human hepatic progenitor‐like cells from postnatal livers successfully repopulated injured livers and exhibited several phenotypes of mature hepatocytes, including susceptibility to HBV. In vitro–expanded CFPHs can be used to characterize the differentiation state of human hepatic progenitor‐like cells. (HEPATOLOGY 2008.)
影响因子：
56.9
作者：
RHIM, JA;SANDGREN, EP;BRINSTER, RL
通讯作者：
BRINSTER, RL
影响因子：
4
作者：
H. Malhi;A. Irani;S. Gagandeep;Sanjeev Gupta
通讯作者：
H. Malhi;A. Irani;S. Gagandeep;Sanjeev Gupta