人类胚胎样体在畸形学中的应用

Anthony Flamier, Supriya Singh, Theodore P. Rasmussen
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引用次数: 2

摘要

人类出生缺陷是相对常见的,可能是由于暴露于环境致畸物或具有致畸活性的药物引起的。人类胚胎干细胞(hESCs)由于其多能性,为致畸原检测和风险评估提供了良好的细胞平台。本单元详细介绍了制备和验证高多能hESCs、生产由hESCs组成的大量聚集的多细胞球体以及这些球体分化为胚状体(EBs)的详细方案。EBs含有多种内胚层、外胚层和中胚层细胞,可以在体外进行复合暴露。因此,它们对检测具有致畸活性的化学物质是有用的。除了描述组装和培养EBs的协议之外,本单元详细介绍了利用EB系统进行致畸评估的方法。此外,还讨论了区分具有真正致畸活性的化合物与单纯毒性的化合物的策略。©2018 by John Wiley &儿子,Inc。
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Use of Human Embryoid Bodies for Teratology

Human birth defects are relatively common and can be caused by exposure to environmental teratogens or to pharmaceuticals with teratogenic activities. Human embryonic stem cells (hESCs), by virtue of their pluripotent nature, provide an excellent cellular platform for teratogen detection and risk assessment. This unit describes detailed protocols for the preparation and validation of highly pluripotent hESCs, the production of large quantities of aggregated multicellular spheroids composed of hESCs, and these spheroids’ differentiation into embryoid bodies (EBs). EBs contain a variety of cells of endodermal, ectodermal, and mesodermal origin and can be subjected to compound exposure in vitro. Hence, they are useful for the detection of chemicals with teratogenic activities. Beyond describing protocols to assemble and culture EBs, this unit details methods to exploit the EB system for teratological assessment. In addition, strategies to distinguish compounds with bona fide teratogenic activity versus simple toxicity are discussed. © 2018 by John Wiley & Sons, Inc.

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