Objective

Due to the increasing prevalence of neurological and cardiovascular disorders possibly related to exposure to environmental toxicants, there is a pressing need to develop reliable and efficient screening tools to identify environmental chemicals that could potentially affect human health. There is a great interest in using stem cell derived cell models for in vitro high-throughput quantitative assays that would allow for detecting the potential hazard of chemicals and prioritizing them for further testing.

 We developed several phenotypic screening assays testing neuronal and cardiac toxicity. Human iPSC-derived cardiomyocytes and neurons were exposed to several known toxic compounds using concentration-responses and various lengths of time. We tested a representative set of compounds that have been known to be associated with neurotoxicity or cardiotoxicity including pesticides, polycyclic aromatic hydrocarbons, and flame retardants. The compound effects were assessed by high-throughput automated imaging and image analysis. The effects on the development of neuronal networks were assessed by quantifying total neurite outgrowth, number of branches and processes, as well as cell viability. The effects on cardiomyocyte cellular and mitochondrial toxicity were assessed by using viability readouts and mitochondrial depolarization probes. We characterized several phenotypic readouts that can be used to determine effective toxic concen