CM attach to one another through specialized portions of the membrane termed intercalated discs. ĬM organization is a critical factor for the coordination of cardiac contractile function. After this period, CM exit the cell cycle, transition to hypertrophic growth, and terminally differentiate, all of which coincides with CM binucleation. In humans, postnatal CM growth is primarily hyperplastic for the first few months after birth as the heart continues to develop. The majority of CM are terminally differentiated due to irreversible cell cycle arrest. CM are constantly subjected to physical stretching as a result of the contractile activity of the heart and contain a large number of mitochondria due to high levels of physiological activity. Sarcomeres are flanked by Z disks, which form a transverse sarcomeric scaffold to efficiently propagate force transmission. CM striations are the result of bundles of myofibrils divided into contractile units, or sarcomeres, comprised of several contractile proteins including actin (thin myofilament) and myosin (thick myofilament). CM are a highly specialized, force-generating, rod-shaped cell type with characteristic striations. Ĭardiac muscle is composed of interconnected cardiomyocytes (CM) layered in an end-to-end pattern forming bundles, termed myofibers, which are adjacent to interstitial fibroblasts, blood vessels and extracellular matrix components. CM toxicity models are critically important because cardiotoxicity is a primary reason drugs fail pre-clinical studies or clinical trials and accounts for the majority of drug recalls. Thus, novel approaches and techniques to improve or restore cardiac function must be developed, including the development of cardiomyocyte (CM) models for in vitro disease modeling, drug screening, cell-based therapies, and toxicity studies. Treatment modalities have been hampered by the fact that the maintenance and repair mechanisms of the heart are limited. The risk of cardiovascular disease also increases with age due to diminished cardiac function associated with age-related morphological and structural changes and loss of cardiomyocytes. Although the death rates of heart disease have declined in the last decade, the disease burden remains high. Despite recent advances in medical and device therapies, there are no effective treatment strategies for heart failure. Over time, coronary heart disease weakens the heart muscle and can lead to heart failure a condition where the heart muscle can no longer generate enough force to efficiently deliver blood to the body. The most common form of heart disease, coronary heart disease, results from a narrowing of the blood vessels due to the buildup of plaque in the arteries. Cardiovascular disease continues to be the leading cause of morbidity and mortality in the United States and the costs associated with the management of these diseases exceeds 300 billion dollars.