Implantation of dendritic cells in injured adult spinal cord results in activation of endogenous neural stem/progenitor cells leading to de novo neurogenesis and functional recovery.
We report a treatment for spinal cord injury involving implantation of dendritic cells (DCs), which act as antigen-presenting cells in the immune system. The novel mechanisms underlying this treatment produce functional recovery. Among the immune cells tested, DCs showed the strongest activity inducing proliferation and survival of neural stem/progenitor cells (NSPCs) in vitro. Furthermore, in DC-implanted adult mice, endogenous NSPCs in the injured spinal cord were activated for mitotic de novo neurogenesis. These DCs produced neurotrophin-3 and activated endogenous microglia in the injured spinal cord. Behavioral analysis revealed the locomotor functions of DC-implanted mice to have recovered significantly as compared to those of control mice. Our results suggest that DC-implantation exerts trophic effects, including activation of endogenous NSPCs, leading to repair of the injured adult spinal cord.
Mikami
Yuji
Y
Neuroimmunology Research Group, Keio University School of Medicine, Tokyo, Japan.
Okano
Hideyuki
H
Sakaguchi
Masanori
M
Nakamura
Masaya
M
Shimazaki
Takuya
T
Okano
Hirotaka James
HJ
Kawakami
Yutaka
Y
Toyama
Yoshiaki
Y
Toda
Masahiro
M
D000818:Animals; D001522:Behavior, Animal; D001710:Biotin / Q000031:analogs & derivatives* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002470:Cell Survival; D003713:Dendritic Cells / Q000637:transplantation*; D003911:Dextrans / Q000378:metabolism; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007124:Immunoenzyme Techniques / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007381:Intermediate Filament Proteins / Q000235:genetics; D008124:Locomotion / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D009474:Neurons / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013119:Spinal Cord Injuries / Q000628:therapy*; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors
D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D008164:Luminescent Proteins; D016177:Macrophage-1 Antigen; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D020933:Neurotrophin 3; D012333:RNA, Messenger; C076397:biotinylated dextran amine; D049452:Green Fluorescent Proteins; D001710:Biotin; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine