Genes, stem cells and biological pacemakers

The advent of gene therapy and cell therapy has led to reconsideration of standard therapies for cardiac disease. One such area of reconsideration is that of the cardiac pacemaker, which has been the mainstay of treatment for high-degree heart block and sinoatrial node dysfunction. Over the past five years, gene therapy has been used to explore the overexpression of beta(2)-adrenergic receptors, the down-regulation of inward rectifier current, and the overexpression of pacemaker current as potential sources of biological pacemakers. Cell therapy approaches have explored the "forcing" of embryonic stem cells to evolve along cardiac (and specifically pacemaker) cell lines and the use of adult mesenchymal stem cells as platforms for delivery of specific gene therapies. This review considers the strengths and weaknesses of each of the approaches used to date and attempts to look to the future of biological alternatives to electronic pacemakers. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.