The newly established human hepatocyte cell line: application for the bioartificial liver
The newly established human hepatocyte cell line: application for the bioartificial liver
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DOI：
10.1016/j.jhep.2004.11.038
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发表时间：
2005-04-01
影响因子：
25.7
通讯作者：
Maehara, Y
中科院分区：
文献类型：
--
作者：
Harimoto, N;Taketomi, A;Maehara, Y
背景/目标：据报道，人类肝细胞系在混合型人工肝支持系统（HALSS）中丧失了许多生化功能。方法：将HSV/tk基因转染人肝母细胞瘤细胞株HepG 2，观察其对肝癌细胞增殖的影响。当HepG 2/tk与组蛋白去乙酰化酶抑制剂（FR 228）和过氧化物酶体增殖物激活受体-γ配体（吡格列酮）一起培养时，评价白蛋白合成和氨去除活性。结果：建立了稳定表达HSV/tk的HepG 2/tk细胞系，并在体内外对更昔洛韦敏感。与FR 228和吡格列酮孵育3天的HepG 2/tk的白蛋白合成速率和氨去除速率均得到改善，这诱导了p21的核转运。与对照组相比，脾内注射用FR 228和吡格列酮预培养3天的HepG 2/tk的大鼠存活时间显著延长。试验组的氨和总胆红素浓度显著低于对照组。结论：HepG 2/tk是安全的，并能提高大鼠的肝功能。这将是一个潜在的细胞来源的霍尔斯在未来。(C)2005年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Human hepatocyte cell lines are reported to lose many of their biochemical functions in a hybrid artificial liver support system (HALSS). Differentiation therapy is useful to up-regulate liver function.Methods: The human hepatoblastoma cell line HepG2 was transfected with HSV/tk gene. Albumin synthesis and ammonia removal activity were evaluated when HepG2/tk was cultured with histone deacetylase inhibitor (FR228) and peroxisome proliferator activated receptor-gamma ligand (pioglitazone). To investigate the function of HepG2/tk in vivo, cell transplantation for 90% hepatectonized rats was conducted.Results: We established stable cell lines which expressed HSV/tk and were sensitive to gancyclovir in vitro and in vivo. Both albumin synthesis rate and ammonia removal rate improved for HepG2/tk incubated with FR228 and pioglitazone for 3 days, which induced nuclear transport of p21. Rats with intrasplenic injection of HepG2/tk precultured for 3 days with FR228 and pioglitazone survived significantly longer than the control rats. The ammonia and total bilirubin concentrations were significantly lower in the test group than in the control group. The injection of gancyclovir inhibited the prolonged survival of the rats with precultured HepG2/tk.Conclusions: HepG2/tk is safe as well as enhancing high levels of liver function. It will be a potential cell source for HALLS in the future. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.