In Vivo Assessment of the Electrophysiological Integration and Arrhythmogenic Risk of Myocardial Cell Transplantation Strategies§

Authors

  • Lior Gepstein,

    Corresponding author
    1. The Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Institute, Technion-Israel Institute of Technology, Haifa, Israel
    • The Sohnis Family Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Institute, Technion-Israel Institute of Technology, POB 9649, Haifa 31096, Israel
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  • Chunhua Ding,

    1. Cardiology Division, Cardiac Electrophysiology and the Cardiovascular Research Institute, University of California, San Francisco, California
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  • Dolkun Rehemedula,

    1. Cardiology Division, Cardiac Electrophysiology and the Cardiovascular Research Institute, University of California, San Francisco, California
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  • Emily E. Wilson,

    1. Cardiology Division, Cardiac Electrophysiology and the Cardiovascular Research Institute, University of California, San Francisco, California
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  • Lior Yankelson,

    1. The Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Institute, Technion-Israel Institute of Technology, Haifa, Israel
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  • Oren Caspi,

    1. The Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Institute, Technion-Israel Institute of Technology, Haifa, Israel
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  • Amira Gepstein,

    1. The Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Institute, Technion-Israel Institute of Technology, Haifa, Israel
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  • Irit Huber,

    1. The Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Institute, Technion-Israel Institute of Technology, Haifa, Israel
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  • Jeffery E. Olgin

    1. Cardiology Division, Cardiac Electrophysiology and the Cardiovascular Research Institute, University of California, San Francisco, California
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Errata

This article is corrected by:

  1. Errata: Erratum to: In Vivo Assessment of the Electrophysiological Integration and Arrhythmogenic Risk of Myocardial Cell Transplantation Strategies Volume 29, Issue 9, 1475, Article first published online: 19 August 2011

  • Author contributions: L.G.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; C.D.: conception and design, collection and/or assembly of data, data analysis and interpretation, final approval of manuscript; D.R.: collection and/or assembly of data, provision of study material; E.E.W.: collection and/or assembly of data, data analysis and interpretation; L.Y.: collection and/or assembly of data, data analysis and interpretation; O.C.: collection and/or assembly of data, final approval of manuscript; A.G.: provision of study material, collection and/or assembly of data; I.H.: collection and/or assembly of data, data analysis and interpretation; J.E.O.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript. L.G. and C.D. are the joint first coauthors.

  • First published online in STEM CELLS EXPRESS October 19, 2010.

  • §

    Disclosure of potential conflicts of interest is found at the end of this article.

Abstract

Cell replacement strategies are promising interventions aiming to improve myocardial performance. Yet, the electrophysiological impact of these approaches has not been elucidated. We assessed the electrophysiological consequences of grafting of two candidate cell types, that is, skeletal myoblasts and human embryonic stem cell-derived cardiomyocytes (hESC-CMs). The fluorescently labeled (DiO) candidate cells were grafted into the rat's left ventricular myocardium. Two weeks later, optical mapping was performed using the Langendorff-perfused rat heart preparation. Images were obtained with appropriate filters to delineate the heart's anatomy, to identify the DiO-labeled cells, and to associate this information with the voltage-mapping data (using the voltage-sensitive dye PGH-I). Histological examination revealed the lack of gap junctions between grafted skeletal myotubes and host cardiomyocytes. In contrast, positive Cx43 immunostaining was observed between donor and host cardiomyocytes in the hESC-CMs-transplanted hearts. Optical mapping demonstrated either normal conduction (four of six) or minimal conduction slowing (two of six) at the hESC-CMs engraftment sites. In contrast, marked slowing of conduction or conduction block was seen (seven of eight) at the myoblast transplantation sites. Ventricular arrhythmias could not be induced in the hESC-CM hearts following programmed electrical stimulation but were inducible in 50% of the myoblast-engrafted hearts. In summary, a unique method for assessment of the electrophysiological impact of myocardial cell therapy is presented. Our results demonstrate the ability of hESC-CMs to functionally integrate with host tissue. In contrast, transplantation of cells that do not form gap junctions (skeletal myoblats) led to localized conduction disturbances and to the generation of a proarrhythmogenic substrate. STEM CELLS 2010;28:2151–2161

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