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原代肝细胞永生化的策略。

Strategies for immortalization of primary hepatocytes.

作者信息

Ramboer Eva, De Craene Bram, De Kock Joery, Vanhaecke Tamara, Berx Geert, Rogiers Vera, Vinken Mathieu

机构信息

Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussel, Belgium.

Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, Technologiepark 927, 9052 Zwijnaarde, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.

出版信息

J Hepatol. 2014 Oct;61(4):925-43. doi: 10.1016/j.jhep.2014.05.046. Epub 2014 Jun 6.

DOI:10.1016/j.jhep.2014.05.046
PMID:24911463
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4169710/
Abstract

The liver has the unique capacity to regenerate in response to a damaging event. Liver regeneration is hereby largely driven by hepatocyte proliferation, which in turn relies on cell cycling. The hepatocyte cell cycle is a complex process that is tightly regulated by several well-established mechanisms. In vitro, isolated hepatocytes do not longer retain this proliferative capacity. However, in vitro cell growth can be boosted by immortalization of hepatocytes. Well-defined immortalization genes can be artificially overexpressed in hepatocytes or the cells can be conditionally immortalized leading to controlled cell proliferation. This paper discusses the current immortalization techniques and provides a state-of-the-art overview of the actually available immortalized hepatocyte-derived cell lines and their applications.

摘要

肝脏具有在受到损伤时进行再生的独特能力。肝脏再生在很大程度上由肝细胞增殖驱动,而肝细胞增殖又依赖于细胞周期循环。肝细胞的细胞周期是一个复杂的过程,受到多种成熟机制的严格调控。在体外,分离的肝细胞不再保留这种增殖能力。然而,通过使肝细胞永生化可以促进体外细胞生长。明确的永生化基因可以在肝细胞中人工过度表达,或者细胞可以被条件性永生化,从而导致可控的细胞增殖。本文讨论了当前的永生化技术,并对实际可用的永生化肝细胞系及其应用提供了最新概述。

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本文引用的文献

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Stem cells, immortalized cells and primary cells in ADMET assays.药物代谢和毒性(ADMET)试验中的干细胞、永生化细胞和原代细胞。
Drug Discov Today Technol. 2006 Spring;3(1):79-85. doi: 10.1016/j.ddtec.2006.03.006.
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FAT10, an ubiquitin-like protein, confers malignant properties in non-tumorigenic and tumorigenic cells.FAT10,一种泛素样蛋白,赋予非致瘤性和致瘤性细胞恶性特性。
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PLoS One. 2013 Apr 23;8(4):e61412. doi: 10.1371/journal.pone.0061412. Print 2013.
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Gene therapy on demand: site specific regulation of gene therapy.按需基因治疗:基因治疗的位点特异性调控。
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Comparison of human hepatoma HepaRG cells with human and rat hepatocytes in uptake transport assays in order to predict a risk of drug induced hepatotoxicity.比较人肝癌 HepaRG 细胞与人及大鼠肝细胞在摄取转运试验中的差异,以预测药物诱导肝毒性的风险。
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