Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block

Yu Feng Hu, James Frederick Dawkins, Hee Cheol Cho, Eduardo Marbán, Eugenio Cingolani

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


Somatic reprogramming by reexpression of the embryonic transcription factor T-box 18 (TBX18) converts cardiomyocytes into pacemaker cells. We hypothesized that this could be a viable therapeutic avenue for pacemakerdependent patients afflicted with device-related complications, and therefore tested whether adenoviral TBX18 gene transfer could create biological pacemaker activity in vivo in a large-animal model of complete heart block. Biological pacemaker activity, originating from the intramyocardial injection site, was evident in TBX18-transduced animals starting at day 2 and persisted for the duration of the study (14 days) with minimal backup electronic pacemaker use. Relative to controls transduced with a reporter gene, TBX18-transduced animals exhibited enhanced autonomic responses and physiologically superior chronotropic support of physical activity. Induced sinoatrial node cells could be identified by their distinctive morphology at the site of injection in TBX18-transduced animals, but not in controls. No local or systemic safety concerns arose. Thus, minimally invasive TBX18 gene transfer creates physiologically relevant pacemaker activity in complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically relevant disease model.

Original languageEnglish (US)
Article number245ra94
JournalScience translational medicine
Issue number245
StatePublished - Jul 16 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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