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European Heart Journal Advance Access originally published online on May 23, 2008
European Heart Journal 2008 29(14):1772-1782; doi:10.1093/eurheartj/ehn216
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Published by Oxford University Press on behalf of the European Society of Cardiology 2008

Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction

Ranil de Silva1,*, Amish N. Raval1, Mohiuddin Hadi2, Karena M. Gildea1, Aylin C. Bonifacino3, Zu-Xi Yu4, Yu Ying Yau5, Susan F. Leitman5, Stephen L. Bacharach2, Robert E. Donahue3, Elizabeth J. Read5 and Robert J. Lederman1

1 Cardiovascular Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, USA
2 Department of Nuclear Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA
3 Haematology Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, USA
4 Pathology Core, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, USA
5 Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

Received 29 September 2007; revised 6 April 2008; accepted 6 May 2008; online publish-ahead-of-print 23 May 2008.

* Corresponding author: NHLI, Imperial College London, Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, UK. Tel: +44 20 73518626, Fax: +44 20 73518629. Email: r.desilva{at}imperial.ac.uk

Aims: In a blinded, placebo-controlled study, we investigated whether intracoronary infusion of autologous mononuclear cells from granulocyte colony-stimulating factor (G-CSF)-mobilized apheresis product or bone marrow (BM) improved sensitive outcome measures in a swine model of large myocardial infarction (MI).

Methods and results: Four days after left anterior descending (LAD) occlusion and reperfusion, cells from BM or apheresis product of saline- (placebo) or G-CSF-injected animals were infused into the LAD. Large infarcts were created: baseline ejection fraction (EF) by magnetic resonance imaging (MRI) of 35.3 ± 8.5%, no difference between the placebo, G-CSF, and BM groups (P = 0.16 by ANOVA). At 6 weeks, EF fell to a similar degree in the placebo, G-CSF, and BM groups (–7.9 ± 6.0, –8.5 ± 8.8, and –10.9 ± 7.6%, P = 0.78 by ANOVA). Left ventricular volumes and infarct size by MRI deteriorated similarly in all three groups. Quantitative positron emission tomography (PET) demonstrated significant decline in fluorodeoxyglucose uptake rate in the LAD territory at follow-up, with no histological, angiographic, or PET perfusion evidence of functional neovascularization. Immunofluorescence failed to demonstrate transdifferentiation of infused cells.

Conclusion: Intracoronary infusion of mononuclear cells from either BM or G-CSF-mobilized apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size, or perfusion in a swine model of large MI.

Key Words: Angiogenesis • Imaging • Myocardial infarction • Myogenesis • Stem cell


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