Stem cells as biological heart pacemakers.
Abnormalities in the pacemaker function of the heart or in cardiac impulse conduction may result in the appearance of a slow heart rate, traditionally requiring the implantation of a permanent electronic pacemaker. In recent years, a number of experimental approaches have been developed in an attempt to generate biological alternatives to implantable electronic devices. These strategies include, initially, a number of gene therapy approaches (aiming to manipulate the expression of ionic currents or their modulators and thereby convert quiescent cardiomyocytes into pacemaking cells) and, more recently, the use of cell therapy and tissue engineering. The latter approach explored the possibility of grafting pacemaking cells, either derived directly during the differentiation of human embryonic stem cells or engineered from mesenchymal stem cells, into the myocardium. This review will describe each of these approaches, focusing mainly on the stem cell strategies, their possible advantages and shortcomings, as well as the avenues required to make biological pacemaking a clinical reality.
Gepstein
Lior
L
Technion-Israel Institute of Technology, The Rappaport Family Institute for Research in the Medical Sciences, Department of Biophysics and Physiology, Bruce Rappaport Faculty of Medicine, 31096 Haifa, Israel. mdlior@tx.technion.ac.il
D001683:Biological Clocks / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000235:genetics / Q000473:pathology / Q000601:surgery; D006801:Humans; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D013234:Stem Cells / Q000502:physiology*