Nature Biotechnology
22, 1282 - 1289 (2004)
Published online: 26 September 2004; | doi:10.1038/nbt1014
Electromechanical integration of cardiomyocytes derived from human embryonic stem cellsIzhak Kehat1, 3, Leonid Khimovich1, Oren Caspi1, Amira Gepstein1, Rona Shofti1, Gil Arbel1, Irit Huber1, Jonathan Satin5, Joseph Itskovitz-Eldor4
& Lior Gepstein1, 2, 31
The Sohnis Family Research Laboratory for the Regeneration of Functional Myocardium, Department of Biophysics and Physiology, the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa, Israel. 2
The Rappaport Family Institute for Research in the Medical Sciences. 3
Department of Cardiology, Rambam Medical Center, Haifa, 31096 Israel. 4
Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, 31096 Israel. 5
Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky, 40536-0298, USA.
Correspondence should be addressed to Lior Gepstein mdlior@tx.technion.ac.ilCell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell−derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies.
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