Engineered electrical conduction tract restores conduction in complete heart block: From in vitro to in vivo proof of concept

Eugenio Cingolani, Vittoria Ionta, Ke Cheng, Alessandro Giacomello, Hee Cheol Cho, Eduardo Marbán

Research output: Contribution to journalArticlepeer-review

Abstract

Background Cardiac electrical conduction delays and blocks cause rhythm disturbances such as complete heart block, which can be fatal. Standard of care relies on electronic devices to artificially restore synchrony. We s ought to create a new modality for treating these disorders by engineering electrical conduction tracts designed to propagate electrical impulses.

Objectives This study sought to create a new approach for treating cardiac conduction disorders by using engineered electrical conduction tracts (EECTs).

Methods Paramagnetic beads were conjugated with an antibody to gamma-sarcoglycan, a cardiomyocyte cell surface antigen, and mixed with freshly isolated neonatal rat ventricular cardiomyocytes. A magnetic field was used to pattern a linear EECT. Results In an in vitro model of conduction block, the EECT was patterned so that it connected 2 independently beating neonatal rat ventricular cardiomyocyte monolayers; it achieved coordinated electrical activity, with action potentials propagating from 1 region to the other via EECT. Spiking the EECT with heart-derived stromal cells yielded stable structures with highly reproducible conduction velocities. Transplantation of EECTs in vivo restored atrioventricular conduction in a rat model of complete heart block.

Conclusions An EECT can re-establish electrical conduction in the heart. This novel approach could, in principle, be used not only to treat cardiac arrhythmias but also to repair other organs.

Original languageEnglish (US)
Pages (from-to)2575-2585
Number of pages11
JournalJournal of the American College of Cardiology
Volume64
Issue number24
DOIs
StatePublished - Dec 23 2014
Externally publishedYes

Keywords

  • arrhythmias
  • cardiac tissue engineering
  • gap junctions
  • heart conduction system

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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