Establishment and Assessment of a New Human Embryonic Stem Cell Based Biomarker Assay for Developmental Toxicity Screening
Presented at the 11th International Conference on Environmental Mutagens (ICEM), March 2013, in Foz do Ignassu, Brazil.
Application of more predictive developmental toxicity screens would aid in reducing the prevalence of birth defects and increase pharmaceutical and chemical safety worldwide. Human embryonic stem (hES) cell technology provides an opportunity for innovative and robust alternative in vitro model systems. Previously, we used high resolution mass spectrometry (HRMS) based metabolomics to discover and test two biomarkers indicative of a metabolic perturbation detected in the culture media that could be used as an early signal for potential developmental toxicity. Here these biomarkers (ornithine and cystine) provide the foundation for the transition to a rapid exposure-based in vitro teratogenicity assay using hES cells. The teratogenic potential of a compound is associated with the level of exposure to the fetus and this approach takes into account the issue of compound exposure in predicting teratogenicity.View PDF