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.
OBJECTIVE
To assess the safety and effects of combined treatment with vascular endothelial growth factor-A(165) plasmid (VEGF-A(165)) and granulocyte- colony stimulating factor (G-CSF) mobilization of bone marrow stem cells in patients with severe chronic ischaemic heart disease (IHD).


RESULTS
Sixteen patients with severe chronic IHD were treated with intramyocardial injections of VEGF-A(165) plasmid followed 1 week later by G-CSF (10 microg/kg/day for 6 days). Two control groups included (i) sixteen patients treated with intramyocardial injections of VEGF-A(165) 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-A(165) and G-CSF treated group, and clinical symptoms were unchanged. There were no side effects to the gene and G-CSF therapy.


CONCLUSIONS
Intramyocardial VEGF-A(165) 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-A(165) and/or use of SDF-1 transfer might be considered.
Ripa
Rasmus Sejersten
RS
Medical Department B, Cardiac Catheterization Laboratory 2014, The Heart Centre, University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark.
Wang
Yongzhong
Y
Jørgensen
Erik
E
Johnsen
Hans Erik
HE
Hesse
Birger
B
Kastrup
Jens
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D015552:Injections, Intralesional; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011446:Prospective Studies; D011994:Recombinant Proteins; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000009:adverse effects
D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor