Abstract 17153: Effects of Age, Sex and Diabetes on Cardiac Stem Cells Characteristics and Left Ventricular Remodeling in Patients with Ischemic Heart Disease
Cardiac stem cells(CSCs) have been utilized in the phase I SCIPIO trial reporting benefits of unexpected magnitude. However, a key question concerns whether a pool of functionally competent CSCs with relevant growth reserve can be harvested from patients independently from age, sex, co-morbidities. Samples were collected from the right atrial appendages of 50 patients undergoing CABG and c-kit-positive CSCs sorted and expanded. This cohort of patients included 34 men and 16 women, 26 had diabetes. Echocardiogram was performed at time of surgery and 6 months later. Age was comparable in men (66±9 years) and women, (72±10 years). 18% more CSCs were obtained from female than male (p =0.006). The yield of CSCs did not vary with age or diabetes. CSC Population Doubling Time (PDT) was higher in men (29±6 hours vs 25±4 hours p<0.05) and in diabetic patients (28.3±7 hours vs 24.3±5 hours p<0.05). Consistently BrdU incorporation was lower in men than in women (9.1±1.2% vs 11.2±2.4%, p<0.05) and in diabetic (7.7±1.8% vs 11.9±3.1%, p<0.05) than in non diabetic. In all cases, CSCs were found to possess the IGF-1-IGF 1R system and 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 death. Regardless of gender and diabetes, telomeres were significantly longer in IGF-1R-positive CSCs, 8.1 kbp, than in cells expressing AT1R, 5.1 kbp. Age 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 (p=0.03). Moreover CSCs telomere length and BrdU incorporation were the only significant predictors of LVR, at multivariate analysis (OR 0.10, CI 0.01-0.94, p=0.02 and OR 0.21, CI 0.05-0.89, p=0.03, respectively). This was not the case when considering IGF-1R positive CSCs. Thus, women possess a larger pool of CSCs, while age and/or diabetes are associated with CSCs characterized by shorter telomeres and reduced growth reserve. Yet, even the old and diabetic myocardium retains a population of fully functional CSCs characterized by the expression of IGF-1R, suggesting that cell therapy may be feasible in the senescent and diabetic human heart.
- © 2012 by American Heart Association, Inc.