Abstract 9633: Human Blood and Cardiac Stem Cells Synergize to Enhance Cardiac Repair When Co-transplanted Into Ischemic Myocardium
Blood-derived circulatory angiogenic cells (CACs) and resident cardiac stem cells (CSCs) have both been shown to improve cardiac function after myocardial infarction (MI). However, whether one cell type is superior has long been an area of speculation with no head-to-head trial. In this study, we compared the effect of human CACs and CSCs, alone or in combination, on myocardial function in an immunodeficient mouse model of MI. Methods and Results- CACs and CSCs were cultured from left atrial appendages and blood samples obtained from patients undergoing clinically-indicated heart surgery. In hypoxic culture conditions designed to mirror ischemic myocardium, protein arrays demonstrated that CACs expressed a broader cytokine profile than CSCs (36 vs. 5, respectively; p<0.05) with 3 cytokines in common. Co-culture of CACs and CSCs further enhanced the production of stromal cell derived factor-1α and vascular endothelial growth factor (p<0.05). Conditioned media promoted equivalent vascular networks and endothelial progenitors recruitment with superior effects using co-cultured conditioned media (p<0.05 vs. single cell cultures). Intramyocardial injection of CACs or CSCs alone improved left ventricular ejection fraction (LVEF) when injected one week after MI (p<0.05 vs. vehicle (PBS) or normal human dermal fibroblasts (NHDF); Figure). Co-transplantation of CACs and CSCs together improved LVEF to a greater extent than either stem cell therapy alone (p<0.05 vs. CAC or CSC injection alone). Conclusions- CACs and CSCs provide unique paracrine repertoires with equivalent effects on angiogenesis, stem cell migration and myocardial repair. Combination therapy with both cell types synergistically improves post infarct myocardial function greater than either therapy alone. This synergy is likely mediated by the complimentary paracrine signatures that promote revascularization and the growth of new myocardium.
- © 2012 by American Heart Association, Inc.