title: Adeno-associated virus-mediated human acidic fibroblast growth factor expression promotes functional recovery of spinal cord-contused rats.
abstract: 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.
authors.affiliation: Centre for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.forename: Huai-Sheng
authors.initials: HS
authors.lastname: Kuo
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Hsu
authors.initials: H
authors.lastname: Ma
authors.forename: Chuan-Wen
authors.initials: CW
authors.lastname: Chiu
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Huang
authors.forename: Lin-Hsue
authors.initials: LH
authors.lastname: Yang
authors.forename: Pei-Teh
authors.initials: PT
authors.lastname: Chang
authors.forename: Yi-Lo
authors.initials: YL
authors.lastname: Lin
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Kuo
authors.forename: Meng-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jiang-Chuan
authors.initials: JC
authors.lastname: Liu
authors.forename: Henrich
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000628:therapy*; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics
chemical_list: D016220:Fibroblast Growth Factor 1