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Versatile synthetic alternatives to Matrigel for vascular toxicity screening and stem cell expansion.
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2017-07-11 , DOI: 10.1038/s41551-017-0096
Eric H Nguyen 1, 2, 3 , William T Daly 1, 2, 4 , Ngoc Nhi T Le 5 , Mitra Farnoodian 3 , David G Belair 1, 6 , Michael P Schwartz 1, 7 , Connie S Lebakken 8 , Gene E Ananiev 9 , Mohammad Ali Saghiri 3 , Thomas B Knudsen 6 , Nader Sheibani 1, 2, 3 , William L Murphy 1, 2, 4, 5
Affiliation  

The physiological relevance of Matrigel as a cell-culture substrate and in angiogenesis assays is often called into question. Here, we describe an array-based method for the identification of synthetic hydrogels that promote the formation of robust in vitro vascular networks for the detection of putative vascular disruptors, and that support human embryonic stem cell expansion and pluripotency. We identified hydrogel substrates that promoted endothelial-network formation by primary human umbilical vein endothelial cells and by endothelial cells derived from human induced pluripotent stem cells, and used the hydrogels with endothelial networks to identify angiogenesis inhibitors. The synthetic hydrogels show superior sensitivity and reproducibility over Matrigel when evaluating known inhibitors, as well as in a blinded screen of a subset of 38 chemicals, selected according to predicted vascular disruption potential, from the Toxicity ForeCaster library of the US Environmental Protection Agency. The identified synthetic hydrogels should be suitable alternatives to Matrigel for common cell-culture applications.

中文翻译:

Matrigel的多功能合成替代品,可用于血管毒性筛查和干细胞扩增。

基质胶作为细胞培养底物和在血管生成测定中的生理相关性经常被质疑。在这里,我们描述了一种基于阵列的合成水凝胶鉴定方法,该凝胶可促进强大的体外血管网络的形成,以检测假定的血管干扰物,并支持人胚胎干细胞的扩增和多能性。我们确定了水凝胶底物,该底物可通过人脐静脉内皮细胞和人诱导的多能干细胞衍生的内皮细胞促进内皮网络的形成,并使用具有内皮网络的水凝胶来鉴定血管生成抑制剂。当评估已知抑制剂时,合成水凝胶显示出比Matrigel更高的灵敏度和可重复性,以及根据预期的血管破坏潜能从美国环境保护署的Toecity ForeCaster库中选择的38种化学物质的子集的盲屏中。对于常见的细胞培养应用,已鉴定出的合成水凝胶应该是Matrigel的合适替代品。
更新日期:2017-07-11
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