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.
Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 30 DEC 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 12, pages 2151–2161, December 2010
How to Cite
Gepstein, L., Ding, C., Rehemedula, D., Wilson, E. E., Yankelson, L., Caspi, O., Gepstein, A., Huber, I. and Olgin, J. E. (2010), In Vivo Assessment of the Electrophysiological Integration and Arrhythmogenic Risk of Myocardial Cell Transplantation Strategies. STEM CELLS, 28: 2151–2161. doi: 10.1002/stem.545
First published online in STEM CELLS EXPRESS October 19, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 30 DEC 2010
- Article first published online: 30 DEC 2010
- Accepted manuscript online: 19 OCT 2010 10:15AM EST
- Manuscript Accepted: 30 SEP 2010
- Manuscript Received: 25 JUN 2008
- Nancy and Stephen Grand Philanthropic Fund
- Yad Hanadiv scholarship
- Israel Science Foundation. Grant Number: #1781/07
Vol. 29, Issue 9, 1475, Article first published online: 19 AUG 2011
- Human embryonic stem cells;
- Fluorescence microscope;
- Embryoid body
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