Combined Sustained Delivery of Basic Fibroblast Growth Factor and Administration of Granulocyte Colony-Stimulationg Factor

Abstract

Purpose: To investigate whether the efficacy of a single angiogenic therapy (sustained delivery of basic fibroblast growth factor [bFGF] or administration of granulocyte colony-stimulating factor [G-CSF]) can be enhanced further by combining the therapies.

Methods: One day after surgical induction of hind-limb ischemia, groups of 6 mice were randomized to receive either no treatment, sustained delivery (SD) of bFGF, endothelial progenitor cell (EPC) mobilization with G-CSF administration, or a combination of bFGF SD+G-CSF administration.

Results: G-CSF administration increased significantly (p<0.05) the number of EPC lineages (CD34+/AC133+ cells) in both peripheral blood and bone marrow compared to no G-CSF administration. The bFGF SD and G-CSF administration individually increased the capillary and arteriole densities significantly versus no treatment (capillary density: 659±48/mm2 and 385±59/mm2, respectively, versus 280±28/mm2; p<0.05; arteriole density: 34±9/mm2 and 41±6/mm2, respectively, versus 15±2/mm2; p<0.05). Importantly, bFGF SD+G-CSF further increased the capillary and arteriole densities compared to either strategy alone (capillary density: 786±40/mm2 versus 659±48/mm2 and 385±59/mm2, respectively, p<0.05; arteriole density: 55±10/mm2 versus 34±9/mm2 and 41±6/mm2, respectively, p<0.05).

Conclusion: This study demonstrates that the combined therapy of sustained bFGF delivery and G-CSF administration potentiates the angiogenic efficacy of either single therapy in mouse hind-limb ischemia models.