European Heart Journal Advance Access originally published online on July 6, 2006
European Heart Journal 2006 27(15):1785-1792; doi:10.1093/eurheartj/ehl117
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Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease
1 Medical Department B, Cardiac Catheterization Laboratory 2014, The Heart Centre, University Hospital Rigshospitalet, DK-2100 Copenhagen Ø, Denmark
2 Department of Radiology, University Hospital Rigshospitalet, Copenhagen, Denmark
3 Department of Haematology, Aalborg University Hospital, Aalborg, Denmark
4 Department of Clinical Physiology, University Hospital Rigshospitalet, Copenhagen, Denmark
Received 11 December 2005; revised 22 May 2006; accepted 2 June 2006; online publish-ahead-of-print 6 July 2006.
* Corresponding author. Tel: +45 3545 2817; fax: +45 3545 2805. E-mail address: jkastrup{at}rh.dk
Aims To assess the safety and effects of combined treatment with vascular endothelial growth factor-A165 plasmid (VEGF-A165) and granulocyte- colony stimulating factor (G-CSF) mobilization of bone marrow stem cells in patients with severe chronic ischaemic heart disease (IHD).
Methods and results Sixteen patients with severe chronic IHD were treated with intramyocardial injections of VEGF-A165 plasmid followed 1 week later by G-CSF (10 µg/kg/day for 6 days). Two control groups included (i) sixteen patients treated with intramyocardial injections of VEGF-A165 plasmid and (ii) sixteen patients treated with intramyocardial injections of placebo. In the G-CSF group, circulating CD34+ stem cells increased almost 10-fold compared with the control groups (P<0.0001). After 3 months, there was no improvement in myocardial perfusion at single photon emission computerized tomography in the VEGF-A165 and G-CSF treated group, and clinical symptoms were unchanged. There were no side effects to the gene and G-CSF therapy.
Conclusion Intramyocardial VEGF-A165 gene transfer followed by bone marrow stem cell mobilization with G-CSF seemed safe. However, a significant increase in circulating stem cells did not lead to improved myocardial perfusion or clinical effects suggesting a neutral effect of the treatment. To improve homing of stem cells, higher doses of VEGF-A165 and/or use of SDF-1 transfer might be considered.
Key Words: Cardiovascular diseases • Gene therapy • Stem cell • Angiogenesis • G-CSF
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