Embryonic stem cell-derived cardiac, neuronal and pancreatic cells as model systems to study toxicological effects

Embryonic stem cell-derived cardiac, neuronal and pancreatic cells as model systems to study toxicological effects
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DOI:
10.1016/j.toxlet.2003.12.064
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发表时间:
2004-04-01
期刊:
影响因子:
3.5
通讯作者:
Wobus, AM
Wobus, AM
中科院分区:
医学3区
文献类型:
--
作者:
Rolletschek, A;Blyszczuk, P;Wobus, AM

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脊椎动物的原代培养物或已建立的细胞系通常用于体外分析化学因子、药物和异生物质的细胞毒性潜力。另一种方法是永久性的多能胚胎干细胞(ES),它能够在体外分化成专门的体细胞类型。在这里,我们证明了ES细胞产生功能性心脏,神经元和胰腺细胞的能力。我们表明,在ES细胞分化,组织特异性基因,蛋白质以及功能特性的表达在发育调控的方式重演早期胚胎发育的过程。我们目前的数据显示,使用ES衍生的心肌细胞和多巴胺能神经元的毒理学研究和ES衍生的胰腺β样细胞在未来的体外试验的潜力。将这些分化系统应用于人类ES细胞,为基础毒理学和应用毒理学开辟了新的前景。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Primary cultures or established cell lines of vertebrates are commonly used to analyse the cytotoxic potential of chemical factors, drugs and xenobiotics in vitro. An alternative approach will be provided by permanent lines of pluripotent embryonic stem (ES) cells, which are able to differentiate into specialised somatic cell types in vitro. Here, we demonstrate the capacity of ES cells to generate functional cardiac, neuronal and pancreatic cells. We show that during ES cell differentiation, tissue-specific genes, proteins as well as functional properties are expressed in a developmentally regulated manner recapitulating processes of early embryonic development. We present data that show the use of ES-derived cardiomyocytes and dopaminergic neurons in toxicological studies and the potential of ES-derived pancreatic beta-like cells in future in vitro assays. The application of these differentiation systems to human ES cells opens up new perspectives in basic and applied toxicology. (C) 2004 Elsevier Ireland Ltd. All rights reserved.