Citation:

Nguyen, E., W. Daly, N. Le, M. Farnoodian, D. Belair, M. Schwartz, C. Lebakken, G. Ananiev, M. Saghiri, T. Knudsen, N. Sheibani, AND W. Murphy. Versatile synthetic alternatives to Matrigel for vascular toxicity screening and stem cell expansion. Nature Communications. Nature Publishing Group, London, Uk, 1(0096):1-34, (2018). https://doi.org/10.1038/s41551-017-0096

Impact/Purpose:

This publication will enhance the reproducibility and consistency of in vitro assays for angiogenesis in the application of predictive toxicology.

Description:

We describe the identification of synthetic hydrogels that promote robust in vitro network formation by human endothelial cells for detecting putative vascular disrupting chemicals. A hydrogel array format identified substrates that promoted endothelial network formation by primary human umbilical vein endothelial cells and endothelial cells derived from human induced pluripotent stem cells. Endothelial networks formed on synthetic hydrogels were used as a screening platform to identify angiogenesis inhibitors and showed superior sensitivity and reproducibility when evaluating known inhibitors. The increased sensitivity of synthetic hydrogels over Matrigel was also observed in a blinded screen of a subset of 38 chemicals from the EPA ToxCast™ library selected by predicted vascular disruption potential. The versatility of the hydrogel array format enabled the identification of synthetic hydrogels that supported human embryonic stem cell expansion and pluripotency. In particular, selected synthetic hydrogels maintained greater or equal expression levels of pluripotency marker NANOG in human embryonic stem cells compared to Matrigel. Despite their relative simplicity and synthetic origin, the synthetic hydrogels identified in the current study are suitable alternatives to Matrigel for multiple common cell culture applications.

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