Getting to the Heart of Myocardial Stem Cells and Cell Therapy

Heart disease is both common and deadly. Cardiovascular disease is a global epidemic, because it is the number 1 cause of death worldwide, and it is estimated that 1 in 3 adults in the United States have cardiovascular disease.1 Although a number of pioneering initiatives have transformed our treatment of cardiovascular disease, new therapies are required to further address the growing incidence of this deadly disease. Intense interest has focused on regenerative medicine as an emerging strategy for chronic diseases such as cardiovascular disease. A number of human tissues, including skin,2 gut, liver,3,–,6 and skeletal muscle3,7 have a tremendous regenerative capacity. For example, skeletal muscle is able to completely restore its cellular architecture and function after an injury that destroys >80% of the muscle.7,8 This regenerative response lacks a fibroproliferative response (ie, formation of scar) and is associated with restoration of the vasculature, myofibers, and extracellular matrix. Compared with skeletal muscle, the regenerative capacity of the adult heart is more limited. Recent studies suggest that the adult heart is capable of cellular turnover and limited regeneration after injury, although the networks that govern this process are ill defined. The use of genetic mouse models and molecular biological techniques is unveiling cell populations, pathways, and extracellular cues that may direct cardiac regeneration and provide a platform for further investigation. The goal of the present review is to examine the endogenous regenerative capacity of the adult heart and highlight new experimental regenerative therapies aimed at restoring myocardial architecture and function. Previous studies have demonstrated that metazoans such as the newt and zebrafish are capable of cardiac regeneration in response to a significant injury.9,–,12 This myocardial regenerative response is complex, and occurs over a 2-month …