Novel Tissue Engineered Tubular Heart Tissue forIn VitroPharmaceutical Toxicity Testing

Abstract

A growing problem in cardiac drug toxicity has been blamed on the lack of adequate testing prior to authorization for prescription use. This study offers an effective alternative to the current method ofin vivopharmaceutical testing, which is time and cost prohibitive. We have accomplished this by developing the novel three-dimensional heart tube model. At the “heart” of our model lies our patented collagen scaffold that enables the cardiac myocytes to display anin vivo–like architecture. The cardiac myocytes were cocultured with the collagen tube for a period of 5 weeks, resulting in the heart tubes. Our heart tubes were treated with specific drugs (nifedipine, isoproterenol, and lidocaine) at varying concentrations. The percent of apoptotic cells was calculated based on observing the number of cells that labeled positive for caspase-3 via confocal microscopy. All three drugs exhibited negative effects at high concentrations in that the number of living cells decreased. Lidocaine showed an increase in apoptosis at concentrations of 75 μM and above. This may indicate that certain drugs have a minimum concentration level that must be reached before the cells experience apoptosis from the toxic levels.