Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease

Objective - Endothelial progenitor cells ( EPCs) that may repair vascular injury are reduced in patients with coronary artery disease ( CAD). We reasoned that EPC number and function may be increased by granulocyte colony- stimulating factor ( G- CSF) used to mobilize hematopoietic progenitor cells in healthy donors. Methods and Results - Sixteen CAD patients had reduced CD34(+)/CD133(+) ( 0.0224 +/- 0.0063% versus 0.121 +/- 0.038% mononuclear cells [ MNCs], P < 0.01) and CD133(+)/ VEGFR-2(+) cells, consistent with EPC phenotype ( 0.00033 +/- 0.00015% versus 0.0017 +/- 0.0006% MNCs, P < 0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out- growth consistent with mature endothelial phenotype ( 2 +/- 1/ well) compared with 16 healthy subjects at high risk ( 13 +/- 4/ well, P < 0.05) or 14 at low risk ( 22 +/- 3/ well, P < 0.001) for CAD. G- CSF 10 mug/ kg per day for 5 days increased CD34(+)/ CD133(+) cells from 0.5 +/- 0.2/muL to 59.5 +/- 10.6/muL and CD133(+)/ VEGFR-2(+) cells from 0.007 +/- 0.004/muL to 1.9 +/- 0.6/muL ( both P < 0.001). Also increased were CD133(+) cells that coexpressed the homing receptor CXCR4 ( 30.4 +/- 8.3/mu L, P < 0.05). Endothelial cell- forming clusters in 10 patients increased to 27 +/- 9/ well after treatment ( P < 0.05), with a decline to 9 +/- 4/ well at 2 weeks ( P = 0.06). Conclusions - Despite reduced EPCs compared with healthy controls, patients with CAD respond to G- CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out- growth in culture.