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Adult Human Stem Cell-Derived Cardiomyocytes: An Alternative Model for Evaluating Chemical and Environmental Pollutant Cardiotoxicity
Citation:
Dreher, K., V. Long, K. Das, AND C. Lau. Adult Human Stem Cell-Derived Cardiomyocytes: An Alternative Model for Evaluating Chemical and Environmental Pollutant Cardiotoxicity. Society of Toxicology, San Antonio, TX, March 11 - 15, 2018.
Impact/Purpose:
no alternative or in vitro testing models exist to rapidly and accurately determine the cardiac effects of chemicals and/or pollutants. This research addresses this need by employing stem cell technology to evaluate the cardiotoxicity of chemicals and pollutants.
Description:
Heart disease is increasing globally with a significant percentage of the increase being attributed to chemical and pollution exposures. Currently, no alternative or in vitro testing models exist to rapidly and accurately determine the cardiac effects of chemicals and/or pollutants. This research addresses this need by employing stem cell technology to evaluate the cardiotoxicity of chemicals and pollutants. Adult human stem cell derived cardiomyocytes (SC-CM) were exposed to either saline, or DMSO vehicle, extracts derived from residual oil fly ash (ROFA) or diesel exhaust particles (DEP) at 1 – 20 µg/ml, suspension of Ag 10 nm nanoparticles (NP, 3 or 6 µg/ml), perfluoroalkyl substances (PFNA, PFOS, PFBS, PFHxS, 25 - 100 µM), or triclosan (TCS, 2.5 – 10 µM) and monitored for viability, beat rate (BR), beat amplitude (BAMP), and beat rate irregularity (BRI) at 0.5, 24, and 48 hr of exposure using the xCELLigence RTCA Cardio platform (ACEA Biosciences). All SC-CMs cultures were challenged with isoproterenol (ISO) after 48 hr of exposure. No chemical or pollutant examined affected SC-CM viability. ROFA and DEP extracts had no effect on SC-CM BR, BAMP, or BRI. ROFA and DEP extracts inhibited ISO stimulation of SC-CM BR and BAMP, respectively, in a dose-response manner. Ag 10 nm NP induced a sustained 15% and 30% decrease in SC-CM BR and BAMP at 3 µg/ml, respectively. PFNA exposure induced an immediate and significant dose-dependent change in SC-CM BR and increase in BRI up to 24 hr of exposure while inhibiting ISO stimulation of SC-CM in a dose-dependent manner. PFOS induced immediate and significant dose-dependent increase in SC-CM BRI over the 48 hr exposure period. TCS exposure induced an immediate increase in SC-CM BR and decrease in BAMP over 48 hr of exposure. TCS inhibited ISO stimulation of SC-CM in a dose-dependent manner. These data demonstrate that adult human SC derived CMs are a viable scalable alternative in vitro testing model to assess a variety of chemicals and environmental pollutants for cardiotoxicity at low concentrations. This model evaluates critical cardiac physiological endpoints that are easily translatable to animal and human studies. (This abstract does not represent EPA policy)