Combined sustained delivery of basic fibroblast growth factor and administration of granulocyte colony-stimulating factor: synergistic effect on angiogenesis in mouse ischemic limbs.
OBJECTIVE
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).


CONCLUSIONS
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.
Jeon
Oju
O
Department of Chemical Engineering, Hanyang University, Seoul, Korea.
Hwang
Ki-Chul
KC
Yoo
Kyung-Jong
KJ
Kim
Byung-Soo
BS
D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000494:pharmacology; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011897:Random Allocation; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016179:Granulocyte Colony-Stimulating Factor