Granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow-derived cells into injured spinal cord and promotes functional recovery after compression-induced spinal cord injury in mice

Granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow-derived cells into injured spinal cord and promotes functional recovery after compression-induced spinal cord injury in mice
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DOI:
10.1016/j.brainres.2007.02.058
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发表时间:
2007-05-29
期刊:
影响因子:
2.9
通讯作者:
Yamazaki, Masashi
Yamazaki, Masashi
中科院分区:
医学3区
文献类型:
--
作者:
Koda, Masao;Nishio, Yutaka;Yamazaki, Masashi

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本研究的目的是阐明粒细胞集落刺激因子(G-CSF)介导的骨髓源性干细胞动员对损伤脊髓的作用。将绿色荧光蛋白(GFP)转基因小鼠的骨髓细胞移植到致死剂量照射的C57 BL/6小鼠中。骨髓移植后4周,在T8水平以20 g,5 min的静态负荷造成脊髓损伤。皮下注射G-CSF(200 μ g/kg/天),持续S天。对GFP和细胞谱系标记物进行免疫组织化学分析,以评估G-CSF介导的骨髓源性细胞动员进入受损脊髓的情况。评估后肢运动恢复6周。免疫组化结果显示,G-CSF可使损伤脊髓内GFP阳性细胞增多,提示骨髓源性细胞被动员并迁移到损伤脊髓内。GFP和胶质细胞标记物的双阳性细胞的数量在G-CSF处理的小鼠中比在对照小鼠中更大。Luxol固蓝染色显示G-CSF促进白色物质保留。与对照小鼠相比,G-CSF处理的小鼠显示出后肢功能的显著恢复。总之,G-CSF通过动员骨髓来源的细胞显示出对脊髓损伤治疗的有效性。(c)2007 Elsevier B. V.保留所有权利。
The aim of the present study was to elucidate the effects of granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of bone marrow-derived stem cells on the injured spinal cord. Bone marrow cells of green fluorescent protein (GFP) transgenic mice were transplanted into lethally irradiated C57BL/6 mice. Four weeks after bone marrow transplantation, spinal cord injury was produced by a static load (20 g, 5 min) at T8 level. G-CSF (200 mu g/kg/day) was injected subcutaneously for S days. Immunohistochemistry for GFP and cell lineage markers was performed to evaluate G-CSF-mediated mobilization of bone marrow-derived cells into injured spinal cord. Hind limb locomotor recovery was assessed for 6 weeks. Immunohistochemistry revealed that G-CSF increased the number of GFP-positive cells in injured spinal cord, indicating that bone marrow-derived cells were mobilized and migrated into injured spinal cord. The numbers of double positive cells for GFP and glial markers were larger in the G-CSF treated mice than in the control mice. Luxol Fast Blue staining revealed that G-CSF promoted white matter sparing. G-CSF treated mice showed significant recovery of hind limb function compared to that of the control mice. In conclusion, G-CSF showed efficacy for spinal cord injury treatment through mobilization of bone marrow-derived cells. (c) 2007 Elsevier B.V. All rights reserved.