Recreating the Sinus Node by Somatic Reprogramming: A Dream Come True?

Electronic pacemakers have been the standard of care for over 50 years for patients with symptomatic bradycardia caused by conditions such as sick sinus syndrome, complete heart block, and congenital heart block. Effective, electronic devices are subject to hardware malfunction, recalls of generators and leads, implantrelated complications and infections. Although the incidence is not high, device-related infections continue to rise, affecting over 2% of device implants and often requiring complete hardware removal and treatment with systemic antibiotics, hospitalization, and placement of a backup temporary pacemaker wire in pacemaker-dependent patients. Another important at-risk population that could benefit from biological pacemakers are fetuses with congenital heart block (frequently related to maternal antiRo/SSA antibodies). Those patients cannot receive intra-uterine electronic devices and frequently develop fatal hydrops-fetalis because of their inability to maintain an adequate heart rate to support the circulation. As an alternative to electronic devices, our group and others have been working for over a decade to develop biological alternatives to electronic pacemakers. Many important contributions have been made to the field, and, despite positive popular press (eg, Briggs), skeptical opinions have been expressed by experts in the field about the prospects of clinical application. The purpose of the present editorial is to review the different biological pacemaker strategies focusing on the potential for human translation.