Electrical Coupling and/or Ventricular Tachycardia Risk of Cell Therapy

Abstract

Electromechanical coupling is crucial in the process of functional cardiomyocyte regeneration. Experimental and initial clinical studies have showed the high risk of arrhythmia in the animals and patients receiving cell transplantation from pluripotent stem cells. The mechanism underlying these arrhythmogenic properties is still unclear. The communications between the cells via gap junction formed by connexin proteins are essential for activating cardiac tissue, allowing propagation of electrical stimuli and related ionic currents. It has been shown that there is a functional gap junction between cardiomyocytes and most cells used for cell transplantation, such as human embryonic stem cells, human mesenchymal stem cells, bone marrow-derived mononuclear cells, and fibroblasts. Although it is still controversial, a recent study has shown that there are N-cadherin- and connexin-43-mediated junctions between skeletal myoblasts and cardiomyocytes, allowing them to induce synchronous beating. However, it should be emphasized that all of the cells mentioned above have been demonstrated to have pro-arrhythmogenic potentials. These factors must be weighed as we pursue the avenues of cell therapy for failed hearts. Experimental studies and initial clinical experience with cell transplantation has opened new perspectives for treatment of irreversibly injured myocardium. It must be pointed out that further studies, including experimental and clinical studies, are necessary to address the questions regarding the efficacy and long-term safety of cell transplantation.