Cardiovascular Research Advance Access first published online on April 23, 2008
This version [Corrected Proof] published online on May 2, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn097
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Colony-stimulating factor-1 transfection of myoblasts improves the repair of failing myocardium following autologous myoblast transplantation
1 Department of Cardio-Thoracic Surgery, Medical University of Vienna, Waehringerguertel 18–20, A-1090 Vienna, Austria
2 Laboratory for Cardiovascular Research, Department of Anatomy and Cell Biology, Medical University of Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria
3 Department of Cardiology, Medical University of Vienna, Waehringerguertel 18–20, A-1090 Vienna, Austria
4 Center for Biomedical Research, Medical University of Vienna, Währingerguertel 18–20, A-1090, Vienna, Austria
5 Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461, USA
* Corresponding author. Tel: +431 4277 61119; fax: +431 4277 61120. E-mail address: seyedhossein.aharinejad{at}meduniwien.ac.at
Aims: Skeletal myoblasts are used in repair of ischaemic myocardium. However, a large fraction of grafted myoblasts degenerate upon engraftment. Colony-stimulating factor-1 (CSF-1) accelerates myoblast proliferation and angiogenesis. We hypothesized that CSF-1 overexpression improves myoblast survival and cardiac function in ischaemia-induced heart failure.
Methods and results: Three weeks following myocardial infarction, rats developed heart failure and received intramyocardial injections of mouse CSF-1-transfected or untransfected primary autologous rat myoblasts, recombinant human CSF-1, mouse CSF-1 expressing plasmids, or culture medium. Tissue gene and protein expression was measured by quantitative RT–PCR (reverse transcription–polymerase chain reaction) and western blotting. Fluorescence imaging and immunocytochemistry were used to analyse myoblasts, endothelial cells, macrophages, and infarct wall thickening. Electrocardiograms were recorded online using a telemetry system. Left ventricular function was assessed by echocardiography over time, and improved significantly only in the CSF-1-overexpressing myoblast group. CSF-1-overexpression enhanced myoblast numbers and was associated with an increased infarct wall thickness, enhanced angiogenesis, increased macrophage recruitment and upregulated matrix metalloproteases (MMP)-2 and -12 in the zone bordering the infarction. Transplantation of CSF-1-overexpressing myoblasts did not result in major arrhythmias.
Conclusion: Autologous intramyocardial transplantation of CSF-1 overexpressing myoblasts might be a novel strategy in the treatment of ischaemia-induced heart failure.
KEYWORDS Heart failure; Myoblasts; Growth factor; Gene therapy
Time for primary review: 15 days
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Cardiovasc Res 2008 79: 355-356.