TY - JOUR
T1 - Engineered electrical conduction tract restores conduction in complete heart block
T2 - From in vitro to in vivo proof of concept
AU - Cingolani, Eugenio
AU - Ionta, Vittoria
AU - Cheng, Ke
AU - Giacomello, Alessandro
AU - Cho, Hee Cheol
AU - Marbán, Eduardo
N1 - Funding Information:
The Cedars-Sinai Medical Center Board of Governors Heart Stem Cell Center supported this study. Dr. Cingolani was supported by a National Institutes of Health / National Center for Advancing Translational Science UCLA CTSI grant ( UL1TR000124 ). Dr. Cho is supported by grants from the American Heart Association ( 12SDG9020030 ) and the National Heart, Lung, and Blood Institute ( 1R01HL111646-01A1 ). Dr. Cheng is supported by a grant from the American Heart Association ( 12BGIA12040477 ). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Cingolani and Ionta contributed equally to this work. Dr. Cho's current address is: Departments of Biomedical Engineering and Pediatrics, Emory University, Atlanta, Georgia.
Publisher Copyright:
© 2014 American College of Cardiology Foundation.
PY - 2014/12/23
Y1 - 2014/12/23
N2 - 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.
AB - 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.
KW - arrhythmias
KW - cardiac tissue engineering
KW - gap junctions
KW - heart conduction system
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U2 - 10.1016/j.jacc.2014.09.056
DO - 10.1016/j.jacc.2014.09.056
M3 - Article
C2 - 25524335
AN - SCOPUS:84917708945
SN - 0735-1097
VL - 64
SP - 2575
EP - 2585
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 24
ER -