Differentiation of liver epithelial (stem-like) cells into hepatocytes induced by coculture with hepatic stellate cells

Differentiation of liver epithelial (stem-like) cells into hepatocytes induced by coculture with hepatic stellate cells
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DOI:
10.1016/s0006-291x(02)00406-0
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发表时间:
2002-05-24
影响因子:
3.1
通讯作者:
Sugiyama, T
Sugiyama, T
中科院分区:
生物学4区
文献类型:
--
作者:
Nagai, H;Terada, K;Sugiyama, T

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肝脏被认为含有可以分化成肝细胞或胆管上皮细胞的干细胞。在本研究中,我们建立了一个非肝细胞上皮细胞系从正常的成年大鼠肝脏。建立的细胞,指定HSL细胞,甲胎蛋白,但既不白蛋白,也不细胞角蛋白19的免疫反应。为了证明HSL细胞在体外的分化潜力,将细胞与肝星状细胞作为混合物或单独使用插入威尔斯孔共培养。因此,尽管与肝星状细胞共培养使HSL细胞能够产生白蛋白,但模拟肝脏环境的混合共培养系统比分离的共培养系统更有效地引起这种现象。总之,HSL细胞具有未成熟的特性和分化为成熟细胞的潜力。不仅细胞外基质,而且可溶性因子,这是由肝星状细胞产生的,诱导这种成熟,表明肝细胞分化的肝环境的重要性。(C)2002 Elsevier Science(美国)。All rights reserved.
The liver is believed to contain stem cells that can differentiate into either hepatocytes or biliary epithelial cells. In the present study, we established a nonhepatocytic epithelial cell line from the normal livers of adult rats. The established cells, designated HSL cells, were immunoreactive against alpha-fetoprotein, but neither albumin nor cytokeratin 19. To demonstrate the differentiation potential of HSL cells in vitro, the cells were cocultured with hepatic stellate cells as a mixture or separately using insert wells. Consequently, although coculture with hepatic stellate cells rendered HSL cells able to produce albumin, the mixed coculture system mimicking the hepatic environment elicited this phenomenon more effectively than the separated coculture system. In conclusion, HSL cells have immature properties and the potential to differentiate into mature cells. Not only the extracellular matrices but also soluble factors, which are produced by hepatic stellate cells, induce this maturation, demonstrating the importance of the hepatic environment for hepatocyte differentiation. (C) 2002 Elsevier Science (USA). All rights reserved.