Abstract 13079: Synergistic Effect of Human Cardiac Stem Cells and Bone Marrow Mesenchymal Stem Cells to Reduce Infarct Size and Restore Cardiac Function
Background: Based upon observations that mesenchymal stem cells (MSCs) induce proliferation and differentiation of c-kit+ cardiac stem cells (CSCs), we hypothesized that co-injection of human c-kit+ (h)CSCs with (h)MSCs produces greater scar size reduction than either cell administered alone in post-MI swine.
Methods: Yorkshire swine (n=20), immunosuppressed with cyclosporine and methylprednisolone, underwent 90-minute occlusion of the LAD coronary artery followed by reperfusion. At 14 days post-MI, thoracoscopic guided intramyocardial injection of either: combination hCSCs / hMSCs (1M/200M, n=5), hCSCs alone (1M, n=5), hMSCs alone (200M, n=5), or placebo (PBS, n=5) were administered to the infarct border zone. Cardiac MRI and pressure volume loops were obtained before and after therapy.
Results: While each cell therapy group had reduced MI size relative to placebo (p<0.05), the MI size reduction was 2-fold greater in combination vs. either cell alone (p<0.05, Fig 1A). Accompanying this enhanced MI size reduction was substantial improvement in LV chamber compliance as assessed by the end-diastolic pressure volume relationship (p<0.01) and improved contractility (preload recruitable stroke work and dP/dtmax, p<0.05) in combination treated swine. Interestingly, EF was restored to baseline in all cell treated pigs, while placebo injected pigs had persistently depressed LV function (p<0.05, Fig 1B). Immunohistochemistry showed robust engraftment of human stem cells in the combination therapy group.
Conclusions: Co-injection of hCSCs with hMSCs produces greater scar size reduction than either cell administered alone, and this combination therapy dramatically improves diastolic function and LV contractility. Taken together these findings illustrate the important biological interactions between c-kit+ CSCs and MSCs that result in substantial enhancement to cell-based therapy; as such these findings have important clinical implications.
- © 2011 by American Heart Association, Inc.