Combined NgR vaccination and neural stem cell transplantation promote functional recovery after spinal cord injury in adult rats.
OBJECTIVE
after spinal cord injury (SCI), there are many adverse factors at the lesion site such as glial scar, myelin-derived inhibitors, cell loss and deficiency of neurotrophins that impair axonal regeneration. Therefore, combination therapeutic strategies might be more effective than a single strategy for promoting functional recovery after SCI. In the present study, we investigated whether a Nogo66 receptor (NgR) vaccine, combined with neural stem cell (NSC) transplantation, could promote better functional recovery than when NgR vaccine or NSCs were used alone.


METHODS
adult rats were immunized with NgR vaccine at 1 week after a contusive SCI at the thoracic level, and the NSCs, obtained from green fluorescent protein transgenic rats, were transplanted into the injury site at 8 weeks post injury. The functional recovery of the animals under various treatments was evaluated by three independent behavioural tests, that is, Basso, Beattie and Bresnahan locomotor rating scale, footprint analysis and grid walking.


RESULTS
the combined therapy with NgR vaccination and NSC transplantation protected more ventral horn motor neurones in the injured spinal cord and greater functional recovery than when they were used alone. Furthermore, NgR vaccination promoted migration of engrafted NSCs along the rostral-caudal axis of the injured spinal cords, and induced their differentiation into neurones and oligodendrocytes in vivo.


CONCLUSIONS
the combination therapy of NgR vaccine and NSC transplantation exhibited significant advantages over any single therapy alone in this study. It may represent a potential new therapy for SCI.
Xu
C-J
CJ
Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xu
L
L
Huang
L-D
LD
Li
Y
Y
Yu
P-P
PP
Hang
Q
Q
Xu
X-M
XM
Lu
P-H
PH
D000375:Aging; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007150:Immunohistochemistry; D009185:Myelin Proteins; D058953:Neural Stem Cells / Q000637:transplantation*; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D014611:Vaccination / Q000379:methods*
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D011994:Recombinant Proteins; C486581:Rtn4r protein, rat