Abstract

Micropatterned-Human Embryo (µ-HUE) Platform for Detection of Human Developmental Toxicity

Yi-Chin Toh, Assistant Professor, National University of Singapore

Unintended exposure to developmentally toxic compounds leads 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 developmentally-toxic 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 a circular multicellular pattern populated with Brachyuary+ cells. Developmentally toxic compounds 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 developmental toxic potential. We could not only measure dose-dependent effects but also correctly classify species-specific drug (Thalidomide) and false negative drug (D-Penicillamine) in mouse embryonic stem cell test. This model offers a scalable screening platform to mitigate the risk of developmentally toxic exposures in human.