Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury.
The well regulated activities of microglia and T cells specific to central nervous system (CNS) antigens can contribute to the protection of CNS neural cells and their renewal from adult neural stem/progenitor cells (aNPCs). Here we report that T cell-based vaccination of mice with a myelin-derived peptide, when combined with transplantation of aNPCs into the cerebrospinal fluid (CSF), synergistically promoted functional recovery after spinal cord injury. The synergistic effect was correlated with modulation of the nature and intensity of the local T cell and microglial response, expression of brain-derived neurotrophic factor and noggin protein, and appearance of newly formed neurons from endogenous precursor-cell pools. These results substantiate the contention that the local immune response plays a crucial role in recruitment of aNPCs to the lesion site, and suggest that similar immunological manipulations might also serve as a therapeutic means for controlled migration of stem/progenitor cells to other acutely injured CNS sites.
Ziv
Yaniv
Y
Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel.
Avidan
Hila
H
Pluchino
Stefano
S
Martino
Gianvito
G
Schwartz
Michal
M
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D002454:Cell Differentiation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009474:Neurons / Q000166:cytology*; D013116:Spinal Cord / Q000166:cytology; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014945:Wound Healing; D000099176:Noggin Protein
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D049452:Green Fluorescent Proteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000099176:Noggin Protein; C571327:Mog protein, mouse