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

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  • Takagi Yasuhiro
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Omura Takashi
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Yoshiyama Minoru
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Matsumoto Ryo
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Enomoto Soichiro
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Kusuyama Takanori
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Nishiya Daisuke
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Akioka Kaname
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Iwao Hiroshi
    Department of Pharmacology, Osaka City University Graduate School of Medical Sciences
  • Takeuchi Kazuhide
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences
  • Yoshikawa Junichi
    Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medical Sciences

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説明

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.<br>

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