A method for human teratogen detection by geometrically confined cell differentiation and migration
Name
Xing-2015-Method for human.pdf
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2.23 MB
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Author(s)
Xing, Jiangwa
Toh, Yi-Chin
Xu, Shuoyu
Yu, Hanry
Date Issued
May 2015
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Xing, Jiangwa, Yi-Chin Toh, Shuoyu Xu, and Hanry Yu. “A Method for Human Teratogen Detection by Geometrically Confined Cell Differentiation and Migration.” Sci. Rep. 5 (May 12, 2015): 10038.
Version
Final published version
Abstract
Unintended exposure to teratogenic compounds can lead to various birth defects; however current animal-based testing is limited by time, cost and high inter-species variability. Here, we developed a human-relevant in vitro model, which recapitulated two cellular events characteristic of embryogenesis, to identify potentially teratogenic compounds. We spatially directed mesoendoderm differentiation, epithelial-mesenchymal transition and the ensuing cell migration in micropatterned human pluripotent stem cell (hPSC) colonies to collectively form an annular mesoendoderm pattern. Teratogens could disrupt the two cellular processes to alter the morphology of the mesoendoderm pattern. Image processing and statistical algorithms were developed to quantify and classify the compounds’ teratogenic potential. We not only could measure dose-dependent effects but also correctly classify species-specific drug (Thalidomide) and false negative drug (D-penicillamine) in the conventional mouse embryonic stem cell test. This model offers a scalable screening platform to mitigate the risks of teratogen exposures in human.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1038/srep10038
