Mechanisms of Myocardial Regeneration

The plasticity of bone marrow-derived progenitor cells (BMPCs) and their ability to acquire the myocyte lineage and regenerate dead myocardium after infarction has been challenged. Similarly, although several laboratories have identified cardiac progenitor cells (CPCs), the controversy concerning myocyte regeneration in the adult heart has not been resolved. The therapeutic efficacy of these 2 classes of progenitor cells depends on their ability to (1) survive in the hostile milieu of the damaged heart, (2) engraft within the myocardium and (3) grow and differentiate. BMPCs may have a growth potential that is superior to that of CPCs, but transdifferentiation could affect this characteristic and CPCs may constitute a more powerful form of therapy for cardiac repair. The process of transdifferentiation may alter the growth behavior of BMPCs, which may result in losing part of their capability of dividing through alterations of the telomere-telomerase system, premature cellular senescence and apoptosis. Moreover, myocytes derived from BMPCs may possess inherent limitations in the acquisition of the adult phenotype. The opposite may also be true and BMPCs may retain a stronger regenerative capacity than CPCs, representing the most appropriate cells for the damaged heart even after transdifferentiation. Ultimately, the question to be addressed is whether BMPCs are superior, equal or inferior to CPCs for the regeneration of cardiomyocytes and coronary vessels in acute and chronic ischemic heart failure. (Circ J 2010; 74: 13-17)