Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia

Wilhelm Roell, Thorsten Lewalter, Philipp Sasse, Yvonne N. Tallini, Bum-Rak Choi, Martin Breitbach, Robert Doran, Ulrich M. Becher, Seong-Min Hwang, Toktam Bostani, Julia von Maltzahn, Andreas Hofmann, Shaun Reining, Britta Eiberger, Bethann Gabris, Alexander Pfeifer, Armin Welz, Klaus Willecke, Guy Salama, Jan W. Schrickel, Michael I. Kotlikoff () and Bernd K. Fleischmann ()
Additional contact information
Wilhelm Roell: Institute of Physiology I, Life and Brain Center,
Thorsten Lewalter: Department of Internal Medicine II,
Philipp Sasse: Institute of Physiology I, Life and Brain Center,
Yvonne N. Tallini: College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401, USA
Bum-Rak Choi: Cardiovascular Research Center, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island 02903, USA
Martin Breitbach: Institute of Physiology I, Life and Brain Center,
Robert Doran: College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401, USA
Ulrich M. Becher: Institute of Physiology I, Life and Brain Center,
Seong-Min Hwang: University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA
Toktam Bostani: Institute of Physiology I, Life and Brain Center,
Julia von Maltzahn: Institute of Genetics,
Andreas Hofmann: Institute of Pharmacology, University of Bonn, Bonn 53105, Germany
Shaun Reining: College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401, USA
Britta Eiberger: Institute of Genetics,
Bethann Gabris: University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA
Alexander Pfeifer: Institute of Pharmacology, University of Bonn, Bonn 53105, Germany
Armin Welz: Department of Cardiac Surgery,
Klaus Willecke: Institute of Genetics,
Guy Salama: University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA
Jan W. Schrickel: Institute of Physiology I, Life and Brain Center,
Michael I. Kotlikoff: College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401, USA
Bernd K. Fleischmann: Institute of Physiology I, Life and Brain Center,

Nature, 2007, vol. 450, issue 7171, 819-824

Abstract: Abstract Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy.

Date: 2007
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DOI: 10.1038/nature06321

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