Pacing the heart with genes: Biological pacing as an alternative to electronic devices

The mammalian heart beats spontaneously without conscious input from the brain. Each heartbeat starts from a minuscule region, called the sinoatrial node (SA node or SAN). The SA node is a small highly-specialized structure containing just a few thousand genuine pacemaker cells. In contrast, the vast majority of the myocardium is populated by the ~5 billion working cardiomyocytes which remain quiescent until the electrical signal propagated from the SAN stimulates them. When the SAN fails, it could lead to circulatory collapse, requiring implantation of electronic pacemaker devices. These electronic devices generally work quite well. However, problems such as lead failure/repositioning, pediatric patients outgrowing the device, finite battery life, and infection call for biologics that are free from all hardware. Toward this goal, we and others have tested the concept of biological pacing. This article focuses on recent breakthroughs in the engineering of biological pacemakers. Combined with efforts to create clinically-relevant, large animal models of biological pacing, the field is moving beyond a conceptual novelty toward a future with clinical reality.