Adeno-associated virus-mediated human acidic fibroblast growth factor expression promotes functional recovery of spinal cord-contused rats
| Autor: | Yi Lo Lin, Meng-Jen Lee, May Jywan Tsai, Pei Teh Chang, Henrich Cheng, Chuan Wen Chiu, Huai Sheng Kuo, Jiang Chuan Liu, Wen Cheng Huang, Wen Chun Kuo, Lin Hsue Yang, Ming Chao Huang, Hsu Ma |
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| Rok vydání: | 2011 |
| Předmět: |
Nervous system
medicine.medical_specialty viruses Genetic Vectors Biology medicine.disease_cause PC12 Cells Green fluorescent protein Rats Sprague-Dawley Dorsal root ganglion Transduction Genetic Neurotrophic factors Internal medicine Drug Discovery Genetics medicine Animals Humans Transgenes Molecular Biology Spinal cord injury Adeno-associated virus Spinal Cord Injuries Genetics (clinical) Neurons Regeneration (biology) Gene Transfer Techniques Recovery of Function Anatomy Dependovirus medicine.disease Spinal cord Rats HEK293 Cells Endocrinology medicine.anatomical_structure Gene Expression Regulation Astrocytes Fibroblast Growth Factor 1 Molecular Medicine Female |
| Zdroj: | The Journal of Gene Medicine. 13:283-289 |
| ISSN: | 1099-498X |
| Popis: | Background Following spinal cord injury, the delivery of neurotrophic factors to the injured spinal cord has been shown to promote axonal regeneration and functional recovery. In previous studies, we showed that acidic fibroblast growth factor (aFGF) is a potent neurotrophic factor that promotes the regeneration of axotomized spinal cord or dorsal root ganglion neurones. Methods We constructed a recombinant adeno-associated virus (AAV) vector to express human aFGF and evaluated aFGF expression and function in AAV-aFGF-infected PC12 cells. We analyzed AAV-green fluorescent protein (GFP) tropism and AAV-mediated aFGF expression in contused spinal cords. Animals received behavioural testing to evaluate the functional recovery. Results Overexpression of aFGF was shown in AAV-aFGF-infected PC12 cells in a dose-dependent manner. Concurrently, neurite extension and cell number were significantly increased in AAV-aFGF infected cells. AAV-mediated GFP expression persisted for at least 5 weeks in contused spinal cords, and the most prominently transduced cells were neurones. Contusive injury reduced endogenous aFGF expression in spinal cords. Overexpression of aFGF was demonstrated in AAV-aFGF transduced spinal cords compared to AAV-GFP transduced spinal cords at 3 and 14 days post-injury. Evaluation of motor function revealed that the improvement of AAV-aFGF-treated rats was prominent. Both AAV-aFGF- and recombinant human aFGF-treated rats revealed significantly better recovery at 5 weeks post-injury, compared to vehicle- and AAV-GFP-treated rats. Conclusions These data suggest that supplement of aFGF improve the functional recovery of spinal cord-contused rats and that AAV-aFGF-mediated gene transfer could be a clinically feasible therapeutic approach for patients after nervous system injuries. Copyright © 2011 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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