G-CSF and HGF: Combination of vasculogenesis and angiogenesis synergistically improves recovery in murine hind limb ischemia
G-CSF and HGF: Combination of vasculogenesis and angiogenesis synergistically improves recovery in murine hind limb ischemia
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DOI：
10.1016/j.yjmcc.2006.11.015
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发表时间：
2007-03-01
影响因子：
5
通讯作者：
Fukuda, Kelichi
中科院分区：
文献类型：
--
作者：
Ieda, Yasuyo;Fujita, Jun;Fukuda, Kelichi
已知粒细胞集落刺激因子(G-CSF)能动员骨髓干细胞进入外周循环。本研究旨在探讨粒细胞集落刺激因子(G-CSF)单独或联合肝细胞生长因子(HGF)对小鼠后肢缺血血管生成和血管生成的促进作用。将绿色荧光蛋白(GFP)转基因小鼠骨髓移植至BALB/c裸鼠或C57/BL6小鼠，造成小鼠后肢缺血。HGF组：缺血肌注射hHGF表达载体。G-CSF组给予G-CSF皮下注射，连续10天。G-CSF+HGF组同时给予G-CSF和HGF治疗，对照组不给予治疗。所有疗效均在4周时得到确认。G-CSF+HGF组的激光多普勒血流灌注指数、微血管密度、后肢坏死率均低于其他组。激光共聚焦显微镜显示缺血区血管内可见大量GFP阳性细胞。部分GFP阳性细胞与α-平滑肌肌动蛋白和von Willebrand因子共同免疫染色。G-CSF动员的干细胞共表达CD49d和CD34，这将促进它们与表达HGF诱导的血管细胞黏附分子-1的缺血肌肉中的细胞的黏附。联合应用G-CSF和HGF有显著的协同作用，提示干细胞从骨髓向外周循环的动员和向缺血区的募集可能促进血管生成和血管生成。(C)2006 Elsevier Inc.保留所有权利。
Granulocyte colony-stimulating factor (G-CSF) is known to mobilize bone marrow stein cells into the peripheral circulation. This study was designed to investigate whether G-CSF by itself or in combination with hepatocyte growth factor (HGF) can promote vasculogenesis and angiogenesis in murine hind limb ischemia. Hind limb ischemia was induced in BALB/c nude or C57/BL6 mice that received bone marrow transplantation from green fluorescent protein (GFP)-transgenic mice. In the HGF group, hHGF expression plasmid was injected into the ischemic muscles. In the G-CSF group, G-CSF was administered subcutaneously for 10 days. The G-CSF+HGF group was concomitantly treated with G-CSF and HGF, and the control group received no treatment. All effects were confirmed at 4 weeks. The G-CSF+HGF group had a higher laser Doppler blood perfusion index, higher microvessel density, and a lower incidence of hind limb necrosis than the other groups. Confocal laser microscopy revealed that a number of GFP-positive cells infiltrated to the vasculature of the ischemic area. Some of the GFP positive cells were clearly co-immunostained with alpha-smooth muscle actin as well as von Willebrand factor. G-CSF-mobilized stem cells co-expressed CD49d and CD34, which would have promoted their adhesion to cells in the ischemic muscle that expressed HGF-induced vascular cell adhesion molecule-1. The combination of G-CSF and HGF had a significant synergistic effect, suggesting that the combination of mobilization of stem cells from bone marrow to peripheral circulation and their recruitment to the ischemic area might potentiate angiogenesis and vasculogenesis. (c) 2006 Elsevier Inc. All rights reserved.