A method for human teratogen detection by geometrically confined cell differentiation and migration
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 embryogenesi...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2015
|
| Online Access: | http://hdl.handle.net/1721.1/97223 https://orcid.org/0000-0002-0339-3685 |
| _version_ | 1826191539791986688 |
|---|---|
| author | Xing, Jiangwa Toh, Yi-Chin Xu, Shuoyu Yu, Hanry |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Xing, Jiangwa Toh, Yi-Chin Xu, Shuoyu Yu, Hanry |
| author_sort | Xing, Jiangwa |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:57:26Z |
| format | Article |
| id | mit-1721.1/97223 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:57:26Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/972232022-09-30T12:24:29Z A method for human teratogen detection by geometrically confined cell differentiation and migration Xing, Jiangwa Toh, Yi-Chin Xu, Shuoyu Yu, Hanry Massachusetts Institute of Technology. Department of Biological Engineering Yu, Hanry 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. Singapore. Agency for Science, Technology and Research Janssen Pharmaceutical Ltd. (Grant R-185-000-182-592) Janssen Pharmaceutical Ltd. (Grant R-185-000-228-592) Singapore-MIT Alliance Computational and Systems Biology Flagship Project (C-382-641-001-091) Mechanobiology Institute, Singapore (R-714-001-003-271) 2015-06-08T18:16:14Z 2015-06-08T18:16:14Z 2015-05 2014-11 Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/97223 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. https://orcid.org/0000-0002-0339-3685 en_US http://dx.doi.org/10.1038/srep10038 Scientific Reports Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Publishing Group |
| spellingShingle | Xing, Jiangwa Toh, Yi-Chin Xu, Shuoyu Yu, Hanry A method for human teratogen detection by geometrically confined cell differentiation and migration |
| title | A method for human teratogen detection by geometrically confined cell differentiation and migration |
| title_full | A method for human teratogen detection by geometrically confined cell differentiation and migration |
| title_fullStr | A method for human teratogen detection by geometrically confined cell differentiation and migration |
| title_full_unstemmed | A method for human teratogen detection by geometrically confined cell differentiation and migration |
| title_short | A method for human teratogen detection by geometrically confined cell differentiation and migration |
| title_sort | method for human teratogen detection by geometrically confined cell differentiation and migration |
| url | http://hdl.handle.net/1721.1/97223 https://orcid.org/0000-0002-0339-3685 |
| work_keys_str_mv | AT xingjiangwa amethodforhumanteratogendetectionbygeometricallyconfinedcelldifferentiationandmigration AT tohyichin amethodforhumanteratogendetectionbygeometricallyconfinedcelldifferentiationandmigration AT xushuoyu amethodforhumanteratogendetectionbygeometricallyconfinedcelldifferentiationandmigration AT yuhanry amethodforhumanteratogendetectionbygeometricallyconfinedcelldifferentiationandmigration AT xingjiangwa methodforhumanteratogendetectionbygeometricallyconfinedcelldifferentiationandmigration AT tohyichin methodforhumanteratogendetectionbygeometricallyconfinedcelldifferentiationandmigration AT xushuoyu methodforhumanteratogendetectionbygeometricallyconfinedcelldifferentiationandmigration AT yuhanry methodforhumanteratogendetectionbygeometricallyconfinedcelldifferentiationandmigration |