Mobilization of haematopoietic and non-haematopoietic cells by granulocyte-colony stimulating factor and vascular endothelial growth factor gene therapy in patients with stable severe coronary artery disease.
OBJECTIVE
To investigate the mobilization of non-haematopoietic and haematopoietic cells from the bone marrow induced by intramyocardial VEGF gene therapy and G-CSF treatment alone or in combination in patients with chronic ischemic heart disease (IHD). Secondly, we tested the hypothesis that the quantity of circulating stem cells correlated with improvement in symptoms.


METHODS
We treated I) 16 patients with intramyocardial placebo injections, II) 16 patients with intramyocardial VEGF-A165 gene injections, III) 13 patients with low dose G-CSF, and IV) 16 patients with intramyocardial VEGF-A165 gene followed by high dose G-CSF.


RESULTS
Circulating CD34+ cells and CD45 CD34 -cells increased by G-CSF in a dose-dependent manner, but did not increase with VEGF gene therapy. The CD45/CD34- cells subgroups increased in both G-CSF treated groups. No association was found between the concentration of mobilized stem cells in the circulation and improvement in symptoms.


CONCLUSIONS
G-CSF mobilized both haematopoietic and non-haematopoietic cells from the bone marrow in a dose-dependent manner in patients with chronic IHD. However, even high levels of circulating stem cells did not improve symptoms of IHD.
Wang
Yongzhong
Y
Cardiac Catheterization Laboratory, The Heart Centre, Copenhagen, Denmark.
Ripa
Rasmus S
RS
Jørgensen
Erik
E
Hesse
Birger
B
Mortensen
Steen
S
Kastrup
Jens
J
D000368:Aged; D018952:Antigens, CD34 / Q000502:physiology; D003324:Coronary Artery Disease / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D017493:Leukocyte Common Antigens / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor; D017493:Leukocyte Common Antigens