TY - JOUR
T1 - Activation of dendritic-like cells and neural stem/progenitor cells in injured spinal cord by GM-CSF
AU - Hayashi, Kaori
AU - Ohta, Shigeki
AU - Kawakami, Yutaka
AU - Toda, Masahiro
N1 - Funding Information:
We thank Dr. H. Okano for providing the nestin-EGFP transgenic mice. We also thank Dr. H.J. Okano for providing Hu antibody. This work was partly supported by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) and the Keio Gijuku Academic Development Funds.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - Dendritic cells
KW - Immune cells
KW - Neural stem cells
KW - Regeneration
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U2 - 10.1016/j.neures.2009.01.018
DO - 10.1016/j.neures.2009.01.018
M3 - Article
C2 - 19428687
AN - SCOPUS:64249102516
SN - 0168-0102
VL - 64
SP - 96
EP - 103
JO - Neuroscience Research
JF - Neuroscience Research
IS - 1
ER -