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.