Abstract 18314: Aging, Diabetes and Ischemic Cardiomyopathy Do Not Deplete the Pool of Cardiac Stem Cells in the Human Heart
The recognition that the heart contains a pool of cardiac stem cells (CSCs) which are self-renewing, clonogenic and multipotent in vitro and in vivo has raised the unique opportunity to employ these cells for the treatment of heart failure. However, a fundamental question concerns whether a pool of functionally competent CSCs with significant growth reserve can be harvested from all patients independently from age, sex, co-morbidities, and type and duration of cardiac disease. Surgical specimens were collected from the atrial or ventricular myocardium of 21 patients and the attempt was made to isolate and expand CSCs to a clinically relevant number. This cohort of patients included 12 women and 9 men affected mostly by ischemic cardiomyopathy; 11 patients also had diabetes. Age was comparable in women, 65±9 years, and men, 65±10 years. Myocardial samples were dissociated, small cardiac cells amplified, and c-kit-positive CSCs collected by immunosorting. Nearly 20% more CSCs were obtained from female than male hearts and this difference was statistically significant. The yield of CSCs harvested from each sample did not vary with age or diabetes. In all cases, CSCs were found to possess the IGF-1-IGF-1R system and all the components of the renin-angiotensin system. Activation of IGF-1R increased CSC proliferation and their resistance to apoptosis, while stimulation of AT1 receptors accelerated cellular senescence and enhanced cell death. Telomeres were significantly longer in IGF-1R-positive CSCs, 8.5 kbp, than in cells expressing AT1R, 4.1 kbp. Additionally, telomerase activity was higher in IGF-1R-positive than AT1R-positive CSCs. Chronological aging was coupled with a 0.6% decrease and a 0.4% increase per year in the fraction of CSCs positive for IGF-1R and AT1R, respectively. Diabetes positively correlated with the expression of AT1R but did not affect IGF-1R expression. Thus, the female heart possesses a larger pool of CSCs, and age and/or diabetes lead to CSCs with shorter telomeres, lower telomerase activity and reduced growth reserve. However, the old and diseased myocardium retains a population of young fully functional CSCs, suggesting that cell therapy by autologous progenitor cells may be feasible in the senescent decompensated human heart.
- © 2010 by American Heart Association, Inc.