Granulocyte-colony stimulating factor augments neovascularization induced by bone marrow transplantation in rat hindlimb ischemia.
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 x 10(7) 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.
Takagi
Yasuhiro
Y
Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences, Osaka, Japan.
Omura
Takashi
T
Yoshiyama
Minoru
M
Matsumoto
Ryo
R
Enomoto
Soichiro
S
Kusuyama
Takanori
T
Nishiya
Daisuke
D
Akioka
Kaname
K
Iwao
Hiroshi
H
Takeuchi
Kazuhide
K
Yoshikawa
Junichi
J
D000469:Alkaline Phosphatase / Q000032:analysis; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000792:Angiography; D000818:Animals; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D017078:Laser-Doppler Flowmetry; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016179:Granulocyte Colony-Stimulating Factor; D000469:Alkaline Phosphatase