Utilizing granulocyte colony-stimulating factor to enhance vascular graft endothelialization from circulating blood cells

Cells in the blood circulating through a vascular graft can contribute to endothelialization of its flow surface. We hypothesized that granulocyte colony-stimulating factor (G-CSF) could enhance this process by increasing circulating bone marrow progenitor cells. Ten dogs received composite grafts that were shielded from any source of endothelialization other than the circulating blood. On the seventh postoperative day and for 7 days thereafter, five dogs were injected subcutaneously with 10 mug/kg/day of human G-CSF. The additional five dogs, used as controls, received no G-CSF. Grafts were retrieved at 4 weeks. All dogs recovered promptly postoperatively. White cell counts in G-CSF dogs increased by an average of 9.5-fold at the end of treatment, and had returned to normal before retrieval. All grafts remained patent. G-CSF grafts had significantly higher endothelialization than the controls (82.2 +/- 9.2% vs. 23.7 +/- 4.4%, p = 0.0004), with extensive flow surface neointima, covered with a single layer of endothelium verified by FVIII/vWF and CD34 staining. Control grafts had virtually no neointima and were covered with a thin layer of fibrin coagulum. Significantly more endothelial-lined microvessels were also found in the G-CSF grafts than in the controls. Dogs treated with G-CSF have increased endothelialization of synthetic vascular grafts due to increased circulating bone marrow progenitor cells.