SBIR Phase I: Metabolomics of Human Embryonic Stem Cells to Predict Teratogenicity: An Alternative Developmental Toxicity Model

This Small Business Innovation Research (SBIR) Phase I project proposes to develop a highly predictive model for assessing the potential of compounds to cause birth defects in the developing human embryo using human embryonic stem (hES) cells as the test substrate. The project proposes to use hES cells and metabolomics to understand the impact of drugs and other chemicals on the development of the human embryo. These cells have the ability to differentiate into any cell in the body and as such, offer the opportunity to study defects in development in a way never available prior to the isolation of hES cells from an embryo. The broader impacts of this research are to increase the safety of compounds and to prevent birth defects resulting from exposure to drugs or other chemicals during pregnancy by more accurately predicting the potential for compounds to cause birth defects. Compound exposure is responsible for 4-5% of all birth defects, yet this is the most preventable type of birth defect. Currently, animal models are used to predict birth defects, however these tests are costly, time-consuming, and are only 60% predictive of the effect on human development. These animal models are the same tests that have been used for more than fifty years to predict the effect of drugs like Thalidomide and Accutane which have caused numerous birth defects in humans. More accurate screens are needed to predict if exposure to specific environmental chemicals or drugs will be hazardous to development.