Granulocyte-Colony Stimulating Factor Augments Neovascularization Induced by Bone Marrow Transplantation in Rat Hindlimb Ischemia

• Published in: Journal of Pharmacological Sciences Vol. 99; no. 1; pp. 45 - 51
• Main Authors: Takagi, Yasuhiro, Omura, Takashi, Yoshiyama, Minoru, Matsumoto, Ryo, Enomoto, Soichiro, Kusuyama, Takanori, Nishiya, Daisuke, Akioka, Kaname, Iwao, Hiroshi, Takeuchi, Kazuhide, Yoshikawa, Junichi
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 2005; The Japanese Pharmacological Society; Elsevier
• Subjects: Alkaline Phosphatase - analysis; angiogenesis; Angiogenesis Inducing Agents - pharmacology; Angiography; Animals; Bone Marrow Transplantation; bone marrow-mononuclear cell transplantation; Cell Proliferation - drug effects; endothelial progenitor cell; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Granulocyte Colony-Stimulating Factor - pharmacology; granulocyte-colony stimulating factor; Hindlimb - blood supply; Hindlimb - drug effects; Hindlimb - metabolism; hindlimb ischemia; Ischemia - physiopathology; Ischemia - therapy; Laser-Doppler Flowmetry; Male; Muscle, Skeletal - blood supply; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Neovascularization, Physiologic - drug effects; Rats; Rats, Inbred Lew; Regional Blood Flow - drug effects; RNA, Messenger - analysis; Time Factors; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; endothelial progenitor cell; granulocyte-colony stimulating factor; bone marrow-mononuclear cell transplantation; angiogenesis; hindlimb ischemia
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.fp0040966

Because granulocyte-colony stimulating factor (G-CSF) mobilizes bone marrow cells including endothelial progenitor cells, we examined whether G-CSF augments angiogenesis and collateral vessel formation induced by bone marrow-mononuclear cells transplantation (BMT). Unilateral hindlimb ischemia was surgically induced in Lewis rats. One week after surgery, administration of 100 mg/kg per day G-CSF significantly increased the laser Doppler blood perfusion index (LDBPI), number of angiographically detectable collateral vessels (angiographic score), and capillary density determined by alkaline phosphatase staining. In the BMT group (1 × 107 cells/rat) and the group with combined G-CSF treatment and BMT, LDBPI was significantly increased compared with that in the vehicle-treated group. In the BMT group, neovascularization was significantly increased as evidenced by the angiographic score and capillary density compared with the vehicle-treated group. Furthermore, the combination of G-CSF treatment and BMT augmented neovascularization compared with BMT alone, as evidenced by the angiographic score and capillary density. Moreover, G-CSF significantly increased vascular endothelial growth factor mRNA and fibroblast growth factor-2 mRNA in hindlimb muscle. In conclusion, G-CSF was found to augment neovascularization in rat hindlimb ischemia. Combined use of G-CSF treatment and BMT may be a useful strategy for therapeutic neovascularization in ischemic tissues.