Co-administration of Autologous Cardiac Stem Cells and Mesenchymal Stem Cells Reduces Infarct Size and is Superior to a Single Cell Type in Restoring Function in a Swine Model of Chronic Ischemic Cardiomyopathy

Introduction: While a cell combination of human mesenchymal stem cells (MSCs) and ckit+ cardiac stem cells (CSCs) improves left ventricular (LV) performance to a greater degree than MSCs alone in post myocardial infarction swine, the impact in heart failure remains unknown. Hypothesis: To advance the development of cell combination therapy, we tested the hypothesis that transendocardial autologous CSCs/MSCs produces greater improvement of performance than autologous MSCs in a rigorous model of heart failure. Methods: Mini-swine (n=28) underwent LAD coronary artery occlusion followed by reperfusion, and allowed to undergo LV remodeling for 90 days. Autologous MSCs were amplified from bone marrow and CSCs from heart biopsies in each swine, and injections of either CSC/MSC combo (1M/200M, n=7), MSCs (200M, n=6), or placebo (Plasmalyte, n=6) were injected to the infarct-border zone via the NOGA system. MRI and pressure volume loops were obtained. Results: Both cell groups had substantially reduced scar size (Combo –37.2± 5.4% vs MSCs –44.1±6.8% vs placebo -12±4.2, P Conclusions: Combination cell therapy and MSCs alone dramatically reduce scar size in swine with chronic ischemic cardiomyopathy. In contrast, combination therapy has much greater impact on functional recovery, increasing EF to [near normal] levels. These findings illustrate that interactions between ckit+ CSCs and MSCs result in substantial enhancement in cardiac performance, establish the safety of autologous cell combination strategies, and support the development of an advanced second generation cell therapeutic product.