title: Engineered electrical conduction tract restores conduction in complete heart block: from in vitro to in vivo proof of concept.
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 sought to create a new modality for treating these disorders by engineering electrical conduction tracts designed to propagate electrical impulses.
  
  
  OBJECTIVE
  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.
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Cingolani
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California; University of Rome "La Sapienza," Rome, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Ionta
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.affiliation: University of Rome "La Sapienza," Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giacomello
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California. Electronic address: heecheol.cho@emory.edu.
authors.forename: Hee Cheol
authors.initials: HC
authors.lastname: Cho
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California. Electronic address: eduardo.marban@cshs.org.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
mesh_terms: D000818:Animals; D054537:Atrioventricular Block / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004574:Electromagnetic Fields; D006329:Heart Conduction System / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D006352:Heart Ventricles / Q000473:pathology*; D018796:Immunoconjugates / Q000494:pharmacology; D066298:In Vitro Techniques; D059346:Magnets; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049031:Sarcoglycans / Q000276:immunology / Q000494:pharmacology; D023822:Tissue Engineering
chemical_list: D018796:Immunoconjugates; D049031:Sarcoglycans
keywords: arrhythmias; cardiac tissue engineering; gap junctions; heart conduction system