Regeneration of spinal cord with cell and gene therapy.
OBJECTIVE
Transplantation of fetal spinal cord cells (FSCC) can promote regeneration of injured spinal cord, while Schwann cells (SC) and some growth factors have a similar effect. However, the synergistic effects and optimal combination of these modalities have not yet been evaluated. In the current study, the efficiency of cell therapy of FSCC and/or SC, with/without growth factors (nerve growth factor [NGF] and brain-derived neurotrophic factor [BDNF]) was examined, with the aim of establishing an optimized protocol for spinal cord injury.


METHODS
One hundred and twenty adult rats were randomly divided into six groups with 20 rats in each group. One week after the thoracic spinal cord injury model had been created, the rats were treated with different therapeutic modalities: Dulbecco's modified Eagles medium (DMEM) in Group I, FSCC in Group II, FSCC plus SC in Group III, FSCC plus SC over-expressing NGF in Group IV, FSCC plus SC over-expressing BDNF in Group V, and FSCC plus SC over-expressing both NGF and BDNF in Group VI. Subsequently, the rats were subjected to behavioral tests once a week after injury, while histology, immunohistochemistry and electron microscopy were performed at one and three month post-operation.


RESULTS
Both SC and FSCC promoted regeneration of spinal cord injury when used separately, while a combination of the two types of cell resulted in better recovery than either alone. Both growth factors (NGF and BDNF) enhanced the outcomes of cell therapy, while synergistic effects meant that a combination of each individual component (group VI) achieved the best results according to locomotion scale, histology and immunoreactivity in the injured cords.


CONCLUSIONS
SC, NGF and BDNF can enhance the outcome of FSCC therapy, while the combination of FSC with SC, NGF and BDNF is possibly the optimal protocol for clinical treatment of acute spinal cord injury.
Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, China. fengsq@hotmail.com
Shi-qing
SQ
Feng
Xiao-hong
XH
Kong
Yang
Y
Liu
De-xiang
DX
Ban
Guang-zhi
GZ
Ning
Jia-tong
JT
Chen
Shi-fu
SF
Guo
Pei
P
Wang
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009416:Nerve Regeneration; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000637:transplantation* / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013904:Thoracic Vertebrae
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors