A Biomarker Based Developmental Toxicity Screen Using Human Induced Pluripotent Stem Cells For Compound Prioritization
Presented at the Society of Toxicology 53rd Annual Meeting, March 2014, in Phoenix, Arizona.
Development of innovative in vitro toxicity screening assays aimed at reducing or replacing the use of animal models in compound safety testing is critical to meet the safety requirements for multiple industries. The current initiatives in Europe (Registration, Evaluation, and Authorization of Chemicals, REACH) and the United States (Tox21) to screen thousands of chemicals currently in use for toxicity require inexpensive and innovative in vitro models to meet their goals. We have created a predictive developmental toxicity screen that can reduce costs, animal use, and can increase pharmaceutical and chemical safety. A small molecule biomarker-based in vitro assay was developed using human induced pluripotent stem (iPS) cells and two metabolites (ornithine and cystine), previously identified as biomarkers of teratogenicity in human embryonic stem (hES) cells (Palmer et al., 2013). The assay uses the ratio of the two metabolites (o/c ratio) to indicate the concentration at which a test compound may perturb cellular metabolism in a manner indicative of teratogenicity.View PDF