The human hepatic cell line HepaRG as a possible cell source for the generation of humanized liver TK-NOG mice.
The human hepatic cell line HepaRG as a possible cell source for the generation of humanized liver TK-NOG mice.
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DOI：
10.3109/00498254.2013.836257
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Suemizu H
中科院分区：
文献类型：
--
作者：
Higuchi Y;Kawai K;Yamazaki H;Nakamura M;Bree F;Guguen-Guillouzo C;Suemizu H
人源化肝脏小鼠，其中肝脏已经用人肝细胞重新填充，已经用于研究人类肝脏生理学的各个方面，例如药物代谢、毒理学和肝炎感染。然而，由于患者源性资源的有限性，人肝细胞的采购是生产人源化肝小鼠的主要问题。为了克服这一限制，将人肝细胞系HepaRG®评估为用于TK-NOG小鼠模型中肝脏重建的有希望的供体细胞。我们证明，在体内，移植的汇合培养物或分化的HepaRG®细胞在受体肝脏内增殖并向肝细胞样细胞和胆汁样细胞分化。相反，增殖的HepaRG®细胞可以移植TK-NOG小鼠肝脏，但只能向胆汁样细胞分化。通过检测受体小鼠血清中的人白蛋白来表征向肝细胞样细胞的分化，并通过人白细胞抗原、人白蛋白、细胞色素P450 3A 4和多药耐药相关蛋白2的免疫组织化学染色来证实。胆管样细胞的特征为细胞角蛋白-19染色阳性。这些结果表明，分化的HepaRG®细胞是用于产生人源化肝脏小鼠的可能的细胞来源，人源化肝脏小鼠是用于肝脏生理学的体内研究的有用模型。
Humanized-liver mice, in which the liver has been repopulated with human hepatocytes, have been used to study aspects of human liver physiology such as drug metabolism, toxicology and hepatitis infection. However, the procurement of human hepatocytes is a major problem in producing humanized-liver mice because of the finite nature of the patient-derived resource. In order to overcome this limitation, the human hepatic cell line HepaRG® were evaluated as promising donor cells for liver reconstitution in the TK-NOG mouse model. We demonstrate that, in vivo, transplanted confluent culture or differentiated HepaRG® cells proliferated and differentiated toward both hepatocyte-like and biliary-like cells within the recipient liver. In contrast, proliferative HepaRG® cells could engraft TK-NOG mouse liver but could differentiate only toward biliary-like cells. The differentiation to hepatocyte-like cells was characterized by the detection of human albumin in the recipient mouse serum and was confirmed by immunohistochemical staining for human leukocyte antigen, human albumin, cytochrome P450 3A4, and multidrug resistance-associated protein 2. Biliary-like cells were characterized by positive staining for cytokeratin-19. These results indicated that the differentiated HepaRG® cells are a possible cell source for generating humanized-liver mice, which are a useful model for in vivo studies of liver physiology.
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影响因子：
46.9
作者：
Azuma, Hisaya;Paulk, Nicole;Grompe, Markus
通讯作者：
Grompe, Markus
影响因子：
29.4
作者：
Parent, R;Marion, MJ;Petit, MA
通讯作者：
Petit, MA
影响因子：
5.8
作者：
YANG, HYL;NAMKUNG, MJ;JUCHAU, MR
通讯作者：
JUCHAU, MR
DOI：
10.1016/j.bbrc.2011.01.042
发表时间：
2011-02-18
影响因子：
3.1
作者：
Hasegawa M;Kawai K;Mitsui T;Taniguchi K;Monnai M;Wakui M;Ito M;Suematsu M;Peltz G;Nakamura M;Suemizu H
通讯作者：
Suemizu H
影响因子：
2
作者：
Machida, Kazuhiko;Suemizu, Hiroshi;Tsuchiya, Toshie
通讯作者：
Tsuchiya, Toshie