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Human Stem Cell-Derived Cardiomyocytes: An Alternative Model to Evaluate Environmental Chemical Cardiac Safety and Development of Predictive Adverse Outcome Pathways
Citation:
Dreher, K. Human Stem Cell-Derived Cardiomyocytes: An Alternative Model to Evaluate Environmental Chemical Cardiac Safety and Development of Predictive Adverse Outcome Pathways. Workshop: ¿The Use of Cardiomyocytes for the Assessment of Proarrhythmic Risk¿, Arlington, VA, October 25 - 26, 2016.
Impact/Purpose:
Assess the impact of chemicals on human heart cells
Description:
Biomonitoring over the last 14 years has shown human exposure to environmental chemicals has increased ~10-fold (1). In addition, mortality and morbidity related cardiovascular disease continues to be the leading national and global public health issue (2, 3). The association between environmental chemical exposure and cardiovascular disease remains uncertain. However, reports on the global composite impact of chemicals exposures on health indicated a 16% of the burden on cardiovascular disease (4, 5). This estimate is consistent with numerous epidemiology, clinical, and toxicological reports indicating the cardiovascular system, at all its various developmental and life stages, is a critical target that can be adversely affected by environmental chemical exposures (6 - 10). The ability to rapidly and accurately assess the cardiac risk of chemicals remains a challenge due to the number of chemicals in the market and emerging chemicals being developed. Human stem cell derived cardiomyocytes provide a potential alternative model to evaluate environmental chemical cardiac toxicity at the physiological, cellular, and molecular levels while providing key information for the development of predictive adverse outcomes pathways (AOP). The presentation will describe preliminary results from various platforms evaluating the effects of chemicals on cardiac: cytotoxicity, physiology, and adult stem cell differentiation using adult human stem cell derived cardiomyocytes. It will also provide a path forward for the development of AOPs predictive of environmental chemical cardiotoxicity. (This abstract does not represent EPA policy)References:1. Centers for Disease Control, NHANES, National Reports on Human Exposure to Environmental Chemicals, 2001 and 2015, www.cdc.gov/exposurereport/.2. www.who.int/mediacentre/factsheets/fs310/en/ 3. www.cdc.gov/nchs/fastats/leading-causes-of-death.htm 4. B. Weinhold, Environ. Health Perspect. 119(4), 2011.5. Prüss-Üstün and Corvalán. WHO Report, PREVENTING DISEASE THROUGH HEALTHY ENVIRONMENTS: Towards an estimate of the environmental burden of disease, 2006.6. Kopf and Walker, J. Environ. Sci. Health C Enviorn. Carcinog. Ecotoxicol. Rev. 27(4), 2009. 7. Navas-Acien et al., Amr. Jour. Epidemiol. 162(1), 2005. 8. Abdou and el-Mazoudy, J. Hazard. Mater. 182(1-3), 2010. 9. Saldana et al., Environ. Health Perspect. 117(9), 2009. 10. Pelclova et al., Hum. Exp. Toxicol. 26(9), 2007.