Repairing damaged myocardium: evaluating cells used for cardiac regeneration

Cellular cardiomyoplasty has raised hopes of regenerating mechanical function in the heart. Several cell sources have been investigated for their ability to repair the damaged heart, providing reason for optimism. Multiple mechanisms have been proposed for the beneficial effects of the delivered cells; however, true reversal of cardiac damage implies the generation of new contractile myocytes. The assessment of a cell's ability to regenerate contractile cells requires a defined set of criteria that, if met, define success. Here we review data from the four primary players in cellular cardiomyoplasty (skeletal myoblasts, bone marrow cells, embryonic stem cells, and resident cardiac stem cells) and assess their potential to differentiate into contractile myocytes as indicated by their ability to meet such specified milestones. Both animal studies and clinical trials suggest that current experimental approaches to cellular cardiomyoplasty yield short-term improvement, although it may be independent of cell type used. However, the mechanisms underlying this salutary effect, as well as its persistence in the longer term, have remained elusive.