Arrhythmia susceptibility in mice after therapy with beta-catenin-transduced hematopoietic progenitor cells after myocardial ischemia/reperfusion

Cardiology. 2009;114(3):199-207. doi: 10.1159/000228644. Epub 2009 Jul 15.

Abstract

Background: Hematopoietic progenitor cells (HPCs) can improve cardiac function after myocardial infarction. However, occurrence of arrhythmias is a potential limitation of cell therapy. In this study, we investigated the cardiac electrophysiological properties of ex vivo expanded HPCs, generated by beta-catenin gene transfer, after transcoronary delivery in a murine model of ischemia/reperfusion (I/R) injury.

Methods and results: To assess arrhythmia inducibility of ex vivo expanded HPCs, mice were subjected to I/R and assigned to sham operation (n = 8), I/R (n = 21) and HPC (n = 15) treatment. Six weeks later, mice were subjected to long-term electrocardiogram recording and in vivo transvenous electrophysiological study. After I/R, mice showed a significant prolongation of conduction and repolarization compared with sham-operated mice. There was a marked increase in ventricular ectopic activity in infarcted mice as compared with sham-operated mice. Cardiac electrophysiological parameters and ventricular ectopic activity were not altered in mice treated with HPCs in comparison with control I/R mice.

Conclusion: Transcoronary delivery of genetically ex vivoexpanded HPCs did not alter the electrophysiological properties in mice after I/R. Therefore, ex vivo beta-catenin-mediated HPC expansion may represent an attractive therapeutic option for cell transplantation treatment of myocardial infarction without electrophysiological side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / etiology*
  • Cell Line
  • Electrocardiography, Ambulatory
  • Electrophysiologic Techniques, Cardiac
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / therapy*
  • Myocardium / pathology
  • Telemetry
  • beta Catenin / genetics*

Substances

  • CTNNB1 protein, human
  • beta Catenin