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Cardiovascular disease continues to bear a significant and increasing burden on global healthcare resources. Despite significant advances in medical and interventional therapies, cardiovascular disease remains the major cause of death worldwide. Beyond this, chronic congestive heart failure (CHF) affects more than 5 million Americans, only half of whom will survive the next five years. These outcomes data have spawned aggressive research efforts searching for novel therapies and treatments of both ischemic heart disease and CHF. Numerous preclinical studies over the past decade have demonstrated the benefit of stem cell therapies with respect to improvement in cardiac function. More recently, research efforts have shifted towards clinical randomized trials examining the role of stem cell therapy in a variety of cardiac conditions. This review focuses on the current status of cardiac cell based therapy while examining the most recent randomized trials including both ischemic and nonischemic cardiomyopathies with an emphasis on current and future application of these novel therapies. Despite ongoing advancements, a variety of obstacles exists and must be addressed prior to widespread clinical implementation of cell-based therapies for the treatment of cardiovascular diseases. regeneration has become an area of intense focus for nearly a decade. Cardiomyocytes, once considered terminally differentiated, have recently been shown capable of limited repair. However, endogenous cardiomyocytes turn over very slowly and cannot efficiently replace damaged myocardium following an ischemic insult [5]. Transplantation of exogenous stem cells into the heart offers the potential to increase the number of cardiomyocytes that are electromechanically coupled and appropriately perfused by newly formed blood vessels [6]. Studies performed to date demonstrate scar size reduction and improved contractility in patients with ischemic cardiomyopathy treated with stem cells with ongoing randomized control trials currently in progress [7]. Cell Sources and Clinical Implications Stem cells are defined as having the capacity to self-renew and to differentiate into specialized cell lines including cardiomyocytes. Numerous human cell populations have been studied experimentally, including induced pluripotent cells, bone marrow derived mononuclear cells, mesenchymal stem cells, mobilized CD34+ cells and more recently, cardiac derived c-kit+ stem cells. Many of these lineages show promise in early cardiac stem cell trials in humans [8]. Embryonic stem cells and induced pluripotent stem cells Embryonic stem cells possess the innate characteristic of pluripotency, the ability to differentiate into all three germ layers while retaining the property of self-renewal or infinite expansion. In animal models, the use of embryonic stem cells in experimentally induced myocardial infarction and nonischemic cardiomyopathies has demonstrated significant improvement in cardiac function and cellular structure with preservation of electrical integration [9,10]. However, their use in the clinical realm has been largely limited not only by ethical concerns related to cell harvesting from early embryonic blastocytes, but also by potential immunologic reactions and the teratogenic potential of infinitely self-renewing cells [6]. Artificially produced induced pluripotent stem (IPS) cells possess many of the beneficial properties of embryonic stem cells and have been refined by reprogramming protocols with the use of microRNAs or recombinant proteins to facilitate differentiation directed toward Rebecca Napier*, Neal L. Weintraub and Adam E. Berman Division of Cardiology, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA *Address for Correspondence Rebecca Napier, MD, Division of Cardiology, Department of Medicine, Medical College of Georgia, Georgia Regents University, 1120 15th Street BBR 6518A, Augusta, GA 30912, E-mail: rnapier@gru.edu Submission: 04 November, 2014 Accepted: 08 December, 2014 Published: 13 December, 2014 Reviewed & Approved by: Dr. Aleksandar Jovanović, Professor of Experimental Medicine, University of Dundee, UK Review Article Open Access

Stem Cell Therapy and the Heart: A Contemporary Review of the Literature