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


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.


CONCLUSIONS
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.
Gardiwal
Ajmal
A
Department of Cardiovascular Medicine, Hannover Medical School, Hannover, Germany.
Reissmann
Lara-Marie
LM
Kotlarz
Daniel
D
Oswald
Hanno
H
Korte
Thomas
T
Landmesser
Ulf
U
Klein
Gunnar
G
Templin
Christian
C
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D002460:Cell Line; D015716:Electrocardiography, Ambulatory; D022062:Electrophysiologic Techniques, Cardiac; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D013686:Telemetry; D051176:beta Catenin / Q000235:genetics*
C495270:CTNNB1 protein, human; D051176:beta Catenin