Research ArticleGene Therapy

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

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Science Translational Medicine  16 Jul 2014:
Vol. 6, Issue 245, pp. 245ra94
DOI: 10.1126/scitranslmed.3008681

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Reprogrammed Heart Cells Set the Pace

Pacemakers have revolutionized the care of patients with slow or abnormal heart rhythms. But these devices can fail by becoming infected or nonfunctional. For these patients, Hu and colleagues created biological pacemakers to serve as a “bridge to device,” providing temporary, hardware-free rhythmic support. Gene transfer of the human embryonic transcription factor T-box 18 (TBX18) to ventricular cardiomyocytes converted, or “reprogrammed,” these cells into pacemaker cells—cells that fire electrical impulses and therefore determine an individual’s heart rate. The authors previously demonstrated TBX18 gene transfer in mice but, in this study, showed that it is feasible in a large-animal model by restoring normal heart rate in pigs with complete heart block. Because the pig’s heartbeat and size are similar to humans, this study represents an important step in translation of this genetic reprogramming approach to the clinic.