Stem Cells and Myocardial Regeneration

Antagonism between stem cells is not new. Competitive mechanisms are known to be critical for the modulation of organ homeostasis and regeneration. Competitive interaction within the niches results in survival of the fittest stem cells and death of the more vulnerable cells. An upregulation of c-myc transforms cells into supercompetitors capable of clonal expansion. The cluster of supercompetitors influences the behavior of the weakest surrounding cells, which are at a growth disadvantage.1 The presence of supercompetitors within niches regulates niche function, and the absence of supercompetitors may alter the preservation of stem cell self-renewal, leading to the generation of old dysfunctional niches.2 However, supercompetitor stem cells may fail to trigger apoptosis in the neighboring aging cells, promoting uncontrolled growth arrest and cellular senescence. This process may become excessive, favoring the formation of crowded niches where old stem cells predominate, opposing the activation of young functionally-competent stem cells. Thus, cooperative cell-to-cell communication may regulate more effectively the fate of stem cells within the niches, because the supporting cells transmit growth signals to stem cells according to the need of the organ and organism.Article see p 213 The concept of cooperation between stem cells and cardiomyocytes, functioning as supporting cells within the myocardial niches, has previously been documented,3 but the study by Williams et al4 in this issue of Circulation reports the cooperation between human mesenchymal stromal cells (MSCs) and human c-kit–positive cardiac stem cells (CSCs) after myocardial infarction in the swine heart. This clever approach has combined the regenerative potential of CSCs with the powerful secretory phenotype of MSCs. The low efficiency of transdifferentiation of MSCs has been overcome by the ability of the delivered CSCs to expand locally and create a large myocyte progeny, together with the required coronary microcirculation.Despite the significant growth reserve …