45. Cardiovascular Cell Therapy

The concept of the heart as a terminally differentiated organ incapable of replacing damaged myocytes has been at the center of cardiovascular research and therapeutic development for the last 50 years. The progressive decline in myocyte number as a function of age and the formation of scarred tissue following myocardial infarction have been interpreted as irrefutable proofs of the postmitotic characteristic of the heart. Emerging evidence supports a more dynamic view of the heart, in which cell death and renewal are vital components of the remodeling process that governs cardiac homeostasis, aging, and disease. In a recent study, myocyte regeneration in the physiologically aging heart was found to occur at previously unexpected levels. From 20 to 100 years of age, the myocyte compartment is replaced completely 15 times in women and 11 times in men, and essentially none of the myocytes present at birth is preserved in the young adult, middle-aged, and senescent heart. The identification of dividing myocytes raises the important question concerning the origin of the newly formed cells. In vitro and in vivo findings strongly suggest that replicating myocytes correspond to transit-amplifying cells derived from the lineage determination of primitive cells, supporting the notion that cardiomyogenesis is controlled by activation and differentiation of stem cells. Investigators in several laboratories concur with the notion that the myocardium is an organ permissive for tissue regeneration mediated by exogenous and/or endogenous progenitors. In this chapter, we will focus on the cell classes that are currently employed in clinical studies for the treatment of cardiac diseases.