Activation of dendritic-like cells and neural stem/progenitor cells in injured spinal cord by GM-CSF
Activation of dendritic-like cells and neural stem/progenitor cells in injured spinal cord by GM-CSF
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DOI：
10.1016/j.neures.2009.01.018
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发表时间：
2009-05-01
影响因子：
2.9
通讯作者：
Toda, Masahiro
中科院分区：
文献类型：
--
作者：
Hayashi, Kaori;Ohta, Shigeki;Toda, Masahiro
在此之前，我们证明了在成年小鼠损伤的脊髓中植入树突状细胞（DC）发挥神经营养作用，导致内源性神经干/祖细胞（NSPCs）的激活和神经发生。粒细胞-巨噬细胞集落刺激因子（GM-CSF）是造血祖细胞生成DC的必需细胞因子，已被证明对脊髓损伤（SCI）的治疗有益。在本研究中，为了评估GM-CSF治疗效果的机制，我们研究了GM-CSF对损伤脊髓中DC样细胞和NSPCs的影响。当GM-CSF注入小鼠损伤的脊髓时，病变部位周围的DC样细胞和活化的小胶质细胞/巨噬细胞的数量增加，伴随着BDNF表达的增加。与对照组相比，GM-CSF治疗组小鼠病变部位周围的内源性NSPCs显著增加。神经球形成实验表明，GM-CSF还能诱导体外培养的NSPCs增殖。此外，脊髓损伤后立即注射GM-CSF可使损伤小鼠的运动功能早期恢复。总之，GM-CSF激活损伤脊髓中的DC样细胞和NSPCs，这可能与其在脊髓损伤病例中的有益作用有关。(C)2009年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Previously, we demonstrated that implanted dendritic cells (DCs) in the injured spinal cord of adult mice exert a neurotrophic effect, resulting in the activation of endogenous neural stem/progenitor cells (NSPCs) and neurogenesis. Granulocyte-macrophage colony stimulating factor (GM-CSF), which is an essential cytokine for the generation of DCs from haematopoietic progenitor cells, has been shown to be beneficial for the treatment of spinal cord injury (SCI). In the present study, to evaluate the mechanisms underlying this therapeutic efficacy of GM-CSF, we investigated the effects of GM-CSF on the DC-like cells and NSPCs in the injured spinal cord. When GM-CSF was injected into the injured spinal cords of mice, the numbers of DC-like cells and activated microglia/macrophages around the lesion site increased, accompanied by an increase in BDNF expression. A significant increase in endogenous NSPCs was observed around the lesion site in the GM-CSF-treated mice compared with that in the controls. A neurosphere forming assay revealed that GM-CSF also induced the proliferation of NSPCs in vitro. Moreover, injection of GM-CSF into the lesion immediately after the SCI resulted in early recovery of the locomotor function of the injured mice. In conclusion, GM-CSF activated DC-like cells and NSPCs in the injured spinal cord, which was probably involved in its beneficial effects in cases of spinal cord injury. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.