title: A method for human teratogen detection by geometrically confined cell differentiation and migration.
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.
authors.affiliation: 1] Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore [2] Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore.
authors.forename: Jiangwa
authors.initials: J
authors.lastname: Xing
authors.affiliation: 1] Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore [2] Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1 EA #03-12, Singapore 117575.
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Toh
authors.affiliation: 1] Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore [2] Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #10-01 CREATE Tower, Singapore 138602, Singapore.
authors.forename: Shuoyu
authors.initials: S
authors.lastname: Xu
authors.affiliation: 1] Institute ofBioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore [2] Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore [3] Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #10-01 CREATE Tower, Singapore 138602, Singapore [4] Department of Physiology, Yong Loo Lin School of Medicine, MD9-04-11, 2 Medical Drive, Singapore 117597, Singapore [5] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Hanry
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D013723:Teratogens / Q000032:analysis / Q000494:pharmacology
chemical_list: D013723:Teratogens