Activation of dendritic-like cells and neural stem/progenitor cells in injured spinal cord by GM-CSF.
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.
Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan.
Kaori
K
Hayashi
Shigeki
S
Ohta
Yutaka
Y
Kawakami
Masahiro
M
Toda
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D039521:CD11c Antigen; D018696:Neuroprotective Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor