Experimental molecular and stem cell therapies in cardiac electrophysiology

One of the most exciting fields in cardiovascular research today involves the possible use of stem cells, cell and gene therapies, and tissue engineering for the treatment of a variety of cardiovascular disorders. Here, we review on the possible applications of these emerging strategies in the field of cardiac electrophysiology. Initially, the elegant cell and gene therapy approaches proposed for the treatment of bradyarrhythmias are described. These gene therapy approaches are mainly focused on the generation of biological pacemakers either by altering the neurohumoral control of existing pacemaking cells (by overexpressing the beta-adrenergic receptor) or by converting quiescent cardiomyocytes into pacemaking cells by shifting the balance between diastolic repolarization and depolarization currents. An alternative approach explores the possibility of grafting pacemaking cells, which were either derived directly during the differentiation of human embryonic stem cells or engineered from mesenchymal stem cells, into the myocardium as a cell therapy strategy for biological pacemaking. We then describe the possible applications of similar strategies for the treatment of common tachyarrhythmias by overexpression of different ion channels, or their modifiers, either directly in host cardiomyocytes or ex vivo in cells that will be eventually transplanted into the heart. Next, we discuss the electrophysiological implications of cardiac stem cell therapy for heart failure. Finally, we address the obstacles, challenges, and avenues for further research required to make these novel strategies a clinical reality.