Assessment of drug induced developmental toxicity using human embryonic stem cells

Assessment of drug induced developmental toxicity using human embryonic stem cells
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DOI:
10.1016/j.cellbi.2008.08.012
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发表时间:
2008-11-01
影响因子:
3.9
通讯作者:
Majumdar, Anish S.
Majumdar, Anish S.
中科院分区:
生物学4区
文献类型:
--
作者:
Mehta, Ashish;Konala, Vijay Bhaskar R.;Majumdar, Anish S.

文献摘要

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胚胎干细胞(ES)是独一无二的,因为它们具有大量产生的潜力和通过胚状体(EB)形成分化成三个胚层的能力。这一特性可作为研究哺乳动物早期发育的指标。我们已经研究了一种全面表征的人ES(hES)细胞系(ReliCell(R)hES 1)用于使用细胞毒性试验测试化合物的胚胎毒性作用的效用。此外,我们进行了真实的时间基因表达分析,以检查药物治疗后胚层标志物表达的变化。结果表明,使用hES细胞的测定可以作为评估化合物的胚胎毒性潜力的可靠、灵敏和稳健的方法。他们还提供了一个概念的证据,hES细胞可以用作体外模型,以证明发育毒性,并检查胚层特异性的影响分化EB。(C)2008年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
Embryonic stem (ES) cells are unique as they have the potential to be generated in large numbers and the ability to differentiate into the three germ layers via embryoid body (EB) formation. This property could be utilized as an index to study initial mammalian development. We have investigated the utility of a comprehensively characterized human ES (hES) cell line (ReliCell (R) hES1) for testing the embryotoxic effects of compounds using cytotoxicity assays. Further, we performed real time gene expression analysis to check the alterations in germ layer markers expression upon drug treatment. The results show that assays using hES cells could serve as a reliable, sensitive and robust method to assess embryotoxic potential of compounds. They also provide a proof of concept that hES cells can be used as an in vitro model to demonstrate developmental toxicity, and to examine the germ layer-specific effects on differentiating EBs. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.