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

Abstract

Objectives. 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. Design. 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.

• Chronic myocardial ischemia
• gene therapy
• stem cell
• angiogenesis
• G-CSF