Cor.At® mouse stem cell-derived cardiomyocytes provide a predictive, standardized, and reproducible cell system for the in vitro assessment of structural carditoxicity (e.g. viability, metabolic impairment). After incubation with test compounds, end points such as neutral red uptake can be used to determine effects which directly affect the viability and integrity of cardiac cells when compared to a non-specific reference cell type, e.g. mouse fibroblasts (see Cor.At@ Tox Neutral Red Uptake assay).
Since cardiac Troponin is considered to be the gold standard biomarker for cardiac injury [1,2], e.g. after myocardial infarction, we have established a cardiac toxicity assay using Cor.At® cardiomyocytes in our standard Cor.At® Tox set-up, but with Troponin release as read-out. After compound treatment, supernatant is collected at various time points (e.g. after 24h, 48h, and 72h), and the amount of Troponin is quantified using a high sensitiviy mouse cardiiac troponin I ELISA kit (e.g. Life Diagnostics, Inc., Cat. No. 2010 1 HS). Troponin release from treated wells is then compared to vehicle-treated, time-mached controls.
[1] Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in laboratory animals
P J O’Brien1, D E C Smith1, T J Knechtel2, M A Marchak2, I Pruimboom-Brees3, D J Brees3, D P Spratt4, F J Archer4, P Butler5, A N Potter1, J P Provost6, J Richard6, P A Snyder3 and W J Reagan3
Laboratory Animals Ltd. Laboratory Animals (2006) 40, 153–171
[2] Serum Troponins as Biomarkers of Drug-Induced Cardiac Toxicity
Kendall B. Wallace, Elizabeth Hausner, Eugene Herman, Gordon D. Holt, James T. Macgregor, Alan L. Metz, Elizabeth Murphy, I.Y. Rosenblum, Frank D. Sistare and Malcolm J. York
Toxicol Pathol 2004; 32; 106