VALIDATION OF MECHANOBIOLOGICAL MARKERS FOR TERATOGEN SCREENING IN DRUG DEVELOPMENT

Abstract

It has been widely reported that teratogen exposure can lead to various birth defects. Compared with other existing models, the micropatterned human pluripotent stem cell model (μP-hPSC) could not only recapitulate spatially controlled differentiation but also collective cell migration. Preliminary testing results showed that the μP-hPSC model was quite sensitive to five known teratogens. However, without a systematic validation of the model using a larger number of compounds, its application in drug safety would be limited. In this study, 18 compounds were tested using our μP-hPSC model, including 10 known human teratogens and 8 non-teratogens. Validation results here show a competitive accuracy, which is over 94% with only one false positive case (Thiamine) while the highest accuracy of other models is around 91%. Together with high prediction accuracy, operational optimization methods proposed in this study will make μP-hPSC model be a more practical screening application.