Scientists injected a genetically-modified virus into guinea pigs to turn part of their heart into a new, working pacemaker. The heartbeat originates within the sinoatrial node (SAN), a small structure containing <10,000 genuine pacemaker cells. If the SAN fails, the ~5 billion working cardiomyocytes downstream of it become quiescent, leading to circulatory collapse in the absence of electronic pacemaker therapy.
The scientists demonstrated the conversion of rodent cardiomyocytes to SAN cells in vitro and in vivo by expression of Tbx18, a gene critical for early SAN specification. Within days of in vivo Tbx18 transduction, 9.2% of transduced, ventricular cardiomyocytes developed spontaneous electrical firing physiologically indistinguishable from that of SAN cells, along with morphological and epigenetic features characteristic of SAN cells. In vivo, focal Tbx18 gene transfer in the guinea-pig ventricle yielded ectopic pacemaker activity, correcting a bradycardic disease phenotype. Myocytes transduced in vivo acquired the cardinal tapering morphology and physiological automaticity of native SAN pacemaker cells.
The creation of induced SAN pacemaker (iSAN) cells opens new prospects for bioengineered pacemakers.