Abstract 15359: Alterations in Ephrin A1/EphA2 Signaling Causes Defects in the Migration of Senescent Human Cardiac Stem Cells

The male human heart loses 64x10^6 myocytes per year indicating that the formation of new cells derived from the differentiation of human cardiac stem cells (hCSCs) is not sufficient to counteract the increase in myocyte death with aging. In this study, we raised the possibility that defective migration of hCSCs to sites of tissue damage contributes to myocardial aging and ventricular dysfunction. In an experimental model of acute infarct, guidance of hCSCs was found to be controlled by the EphA2 receptor tyrosine kinase. Activation of EphA2-positive hCSCs with ephrin A1 promoted the mobilization of hCSCs to the ischemic region enhancing myocardial regeneration. To study the effects of aging on hCSC migration, we have employed two models of cellular senescence: replicative senescence of serially-passaged hCSCs and stress-induced senescence of hCSCs exposed to doxorubicin. To validate our strategies, several parameters were evaluated. In both cases, hCSCs showed a flattened morphology and displayed nuclear...