Molecular and cellular prospects for repair, augmentation, and replacement of the failing heart

Molecular and cellular biology offer the promise of new approaches to the treatment of heart failure. This article discusses the basic science background, the current state of investigation, and the potential for therapeutic application of these new sciences. It also emphasizes the limitations and unknowns in this frontier. Three approaches are presented: First, increasing the number of myocytes in the heart, previously held to be untenable because postnatal cardiomyocytes do not divide, may be possible by regulating the cell cycle to reinduce cardiac growth. Also, nonmyocytes extant in the heart may be coaxed into differentiating into cardiomyocytes, or exogenous muscle cells may be grafted into the myocardium. Second, cardiac function may be augmented by molecular therapies that increase contractile protein function or regulate beta-adrenergic receptors or Ca++ channels. Third, improved prospects for transplantation of the failed heart may occur by genetic modification of a xenograft donor heart that reduces the chance of immune rejection by the human recipient. The formulation for the successful application of any of these therapies depends on not only the creativity of scientists but also the wisdom of physicians.