Stem cell therapy for heart failure.

Heart failure (HF) is a chronic disease and a significant global public health concern. Current medical treatment for HF can reduce symptoms but does little to decrease mortality and the need for cardiac transplantation. Novel therapies are needed to further decrease mortality and limit or eliminate the need for cardiac transplantation. Recently, several basic science and clinical trials have suggested that enhancing endogenous regeneration (repair) and exogenous cell therapy might be an approach to improve the function of the failing heart. This article reviews cell therapy clinical trials in patients with chronic HF. The three major subgroups of cells being studied in phase 1 and beginning phase 2 trials are skeletal myoblasts, bone marrow-derived mononuclear cells, and enriched subpopulations of bone marrow and cardiac stem cells. Techniques for stimulating upregulation of endogenous bone marrow progenitor cells in the circulating blood have raised serious safety issues and need to be carefully evaluated. Intracoronary infusion and both transepicardial and transendocardial direct injection of stem cells have been tested clinically and shown to be safe. Skeletal myoblast implantation has led to improved cardiac function, but studies show formation of skeletal muscle in the heart and a lack of electrical integration with surrounding myocardium, a cause for concern. Bone marrow-derived mononuclear cells and enriched subpopulations of cardiac and bone marrow stem cells have been studied extensively in animals and in recent clinical trials, with both controversy and success. There is still much room for improvement, but animal and human studies of enriched subpopulations of cardiac and bone marrow stem cells have shown that these cells are safe, have significant capability for cardiac repair, and offer the best chance for legitimate medical therapy for patients with chronic HF.