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THE STUDY OF INTRASPINAL IMPLANTATION OF NEUROTROPHIN-3 MODIFIED OLFACTORY ENSHEATHING GLIA IN THE R |
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Saturday, 24 December 2005 |
Tian-Sheng Sun
The Department of Orthopedics, Beijing Army General Hospital, 5 Nancanmen, Dongcheng District, Beijing 100700, China.
Objectives: The present study combines olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin-3 (NT-3) gene therapy in an attempt to enhance regeneration after thoracic spinal cord injury of rat. At the same time, we observe the results of functional restoration after the OEG transplantation to patients with SCI.
Methods: (1) Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pEGFP-NT3 and subsequently implanted into adult Wistar rats directly after contusion of the thoracic spinal cord (T9). Implanted animals received a total of 4?05 OEG that were subjected to transfection with pEGFP-NT3, pEGFP, or no plasmid, respectively. The survival and gene expression of OEG ex vivo and in vivo was observed, and the locomotion was evaluated. (2) Patients with SCI were performed OEG transplantation according to enrolment standard and were followed up.
Results: (1) The basic experiment showed that locomotion behaviour had improved 12 weeks postoperatively. The BBB locomotion score of NT-3 transfected group is higher than that of other groups during all period. The number of nerve fiber of lesion region in NT-3 transfected group was the largest among all groups. A great number of OEG expressing GFP were observed around spinal injury area through the fluorescence microscope. Gene expression of OEG ex vivo and in vivo was proven. (2) The clinical study revealed sensory function of patients had improvement while locomotion function had little change.
Conclusion: (1) OEG may be better candidates for neurotrophic factor delivery since they can reduce the problem of regenerating axons to re-enter the distal part of the spinal cord and have advantages over the use of Schwann cells and fibroblasts. In current study, our results demonstrate that genetic engineering of OEG not only resulted in a cell that was more effective in promoting axonal outgrowth but could also lead to enhanced recovery after injury. (2) For spinal cord contusion, OEG can cause little recovery of locomotion function in our clinical study.
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