Granulocyte-colony stimulating factor augments neovascularization induced by bone marrow transplantation in rat hindlimb ischemia
Granulocyte-colony stimulating factor augments neovascularization induced by bone marrow transplantation in rat hindlimb ischemia
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DOI：
10.1254/jphs.fp0040966
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发表时间：
2005-09-01
影响因子：
3.5
通讯作者：
Yoshikawa, J
中科院分区：
文献类型：
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作者：
Takagi, Y;Omura, T;Yoshikawa, J
由于粒细胞集落刺激因子（G-CSF）动员骨髓细胞，包括内皮祖细胞，我们研究了G-CSF是否增强骨髓单核细胞移植（BMT）诱导的血管生成和侧支血管形成。在刘易斯大鼠中手术诱导单侧后肢缺血。术后1周，每天给予100 mg/kg G-CSF显著增加了激光多普勒血液灌注指数（LDBPI）、血管造影可检测的侧支血管数量（血管造影评分）和通过碱性磷酸酶染色测定的毛细血管密度。在BMT组（1 × 10（7）个细胞/大鼠）和G-CSF联合BMT治疗组中，LDBPI与溶剂治疗组相比显著增加。在BMT组中，与溶剂处理组相比，血管造影评分和毛细血管密度证明新血管形成显著增加。此外，G-CSF治疗和BMT的组合增强了新生血管形成与BMT单独相比，证明了血管造影评分和毛细血管密度。此外，G-CSF显著增加后肢肌肉中血管内皮生长因子mRNA和成纤维细胞生长因子-2 mRNA。总之，G-CSF被发现增加大鼠后肢缺血的新血管形成。联合使用G-CSF治疗和骨髓移植可能是治疗缺血组织新生血管的有效策略。
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.