Development of In Vitro Toxicology Assays using Human Pluripotent Stem Cells and Targeted Metabolomics
There is an immediate need to develop predictive, inexpensive, and high throughput toxicity assays that reduce or replace animal use in chemical safety screening for multiple industries, as well as to support ongoing initiatives to determine the toxicity profile for chemicals currently in use. Establishing predictive human cell-based assays to aid in the early discovery-phase detection of potential toxicants is strongly warranted as these tests could reduce product development time and costs. Assays developed should allow selection and prioritization of the most promising chemicals for further development and reduce the number animals required for toxicity testing. Stemina Biomarker Discovery, Inc. has developed two in vitro toxicology assays, devTOX quickPredict and Cardio quickPredict, that utilize human pluripotent stem (hPS) cells or their derivatives and targeted metabolomics to address these needs. The devTOX quickPredict assay predicts a chemical’s developmental toxicity potential based on the metabolic perturbation of two biomarkers, ornithine and cystine, in hPS cells. The assay predicted the developmental toxicity potential across a diverse set of more than 100 chemicals with 86% accuracy. The second assay, Cardio quickPredict, predicts a chemical’s cardiovascular liability based on changes in human iPSC-derived cardiomyocytes (iPSC-CM) metabolism and cell viability and can identify both functional and structural cardiotoxicants. The assay’s prediction model (PM) is based on the response of three metabolite ratios (viability (VIA)/lactate (LAC), thymidine (THY)/arachidonic acid (ARA), and N-acetylaspartate (NAA)/2’-deoxycytidine (2DC)) and predicts the concentration a chemical exhibits cardiotoxicity potential. The PM classified 78 chemicals with known outcomes (49 cardiotoxic, 29 non-cardiotoxic) with 87% accuracy. This webinar will discuss the development process for these assays and describe their application in toxicology testing.
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