Stem Cell Therapy for Cardiac Diseases

Abstract

Even successfully revascularized hearts undergo ventricular remodeling, a process of neurohormonal imbalance and apoptosis that leads to ischemic heart failure. Until recently, cardiologists believed that ventricular remodeling was irreversible and that the heart had no capacity for self-renewal. It now appears that the injured heart may be repaired by resident cardiac stem cells and by stem cells that originate from bone marrow. Stem cells have a capacity for self-renewal and can sustain, generate, and replace any terminally differentiated cell in the body. The adult bone marrow is a reservoir of stem cells that have enormous plasticity. By promoting angiogenesis, stem cell therapy may improve left ventricular function or relieve angina in patients with acute or chronic coronary artery disease. At present, research and clinical interest is largely devoted to skeletal myoblasts and autologous bone-marrow mononuclear cells (ABMMNCs). Skeletal myoblasts offer myocyte replacement therapy for scarred myocardial segments, and ABMMNCs offer neoangiogenesis and regenerative therapy for acute and chronic ischemic heart disease involving viable myocardial tissue. Early clinical trials using these cells have yielded promising initial results regarding safety and efficacy. Stem cells may be delivered through coronary arteries, through coronary veins, or by means of peripheral-vein infusion. Alternatively, direct intramyocardial injection may be performed, utilizing a surgical, transendocardial, or transvenous approach. Also, a delivery strategy may involve mobilization of stem cells from the bone marrow by means of cytokine therapy, with or without peripheral harvesting. Intracoronary infusion is the most widely used cell delivery method in the clinical setting, especially after an acute myocardial infarction (AMI). Stem cells delivered 4 to 9 days after an AMI have been associated with a good safety profile. The technique is similar to that used for coronary angioplasty. Intramyocardial injection is the preferred delivery route in patients with chronic total occlusion of coronary arteries or chronic congestive heart failure. Intramyocardial injection can be performed as a transepicardial, transendocardial, or transcoronary venous injection. The transendocardial route allows therapy to be precisely targeted. Targeted therapy is gaining importance as the ineffectiveness of injecting ABMMNCs into scar tissue becomes increasingly evident. Skeletal myoblast therapy is used for ischemic heart failure with areas of nonviable myocardium or scar tissue and compromised systolic left ventricular function. The recent release of the 1-year results of the TOPCAREAMI trial confirmed the overall safety of stem cell therapy after an AMI. Although ventricular arrhythmias are a potential concern with skeletal myoblasts, this complication has not been observed with ABMMNCs. Nevertheless, the latter cells may cause accelerated atherogenesis or myocardial calcification. Investigations are underway at the molecular level to elucidate the mechanisms of stem cell therapy, which are attributed to transdifferentiation versus cell fusion. In animal models of ischemic heart disease, stem cell therapy appears to increase neovascularization. Clinically, the next step in cardiac cell therapy is to answer basic questions, such as whom should be treated, when treatment should be initiated, and what products are ideal in each clinical scenario. KeywordsMesenchymal Stem CellLeft Ventricular Ejection FractionAcute Myocardial InfarctionEndothelial Progenitor CellStem Cell TherapyThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.