title: Adenoviral vector carrying glial cell-derived neurotrophic factor for direct gene therapy in comparison with human umbilical cord blood cell-mediated therapy of spinal cord injury in rat.
abstract: METHODS
  Experimental study.
  
  
  OBJECTIVE
  To evaluate the treatment of spinal cord injury with glial cell-derived neurotrophic factor (GDNF) delivered using an adenoviral vector (AdV-GDNF group) in comparison with treatment performed using human umbilical cord blood mononuclear cells (UCB-MCs)-transduced with an adenoviral vector carrying the GDNF gene (UCB-MCs+AdV-GDNF group) in rat.
  
  
  METHODS
  Kazan, Russian Federation.
  
  
  METHODS
  We examined the efficacy of AdV-GDNF and UCB-MCs+AdV-GDNF therapy by conducting behavioral tests on the animals and morphometric studies on the spinal cord, performing immunofluorescence analyses on glial cells, investigating the survival and migration potential of UCB-MCs, and evaluating the expression of the recombinant GDNF gene.
  
  
  RESULTS
  At the 30th postoperative day, equal positive locomotor recovery was observed after both direct and cell-based GDNF therapy. However, after UCB-MCs-mediated GDNF therapy, the area of preserved tissue and the number of spared myelinated fibers were higher than those measured after direct GDNF gene therapy. Moreover, we observed distinct changes in the populations of glial cells; expression patterns of the specific markers for astrocytes (GFAP, S100B and AQP4), oligodendrocytes (PDGFαR and Cx47) and Schwann cells (P0) differed in various areas of the spinal cord of rats treated with AdV-GDNF and UCB-MCs+AdV-GDNF.
  
  
  CONCLUSIONS
  The differences detected in the AdV-GDNF and UCB-MCs+AdV-GDNF groups could be partially explained by the action of UCB-MCs. We discuss the insufficiency and the advantages of these two methods of GDNF gene delivery into the spinal cord after traumatic injury.
authors.affiliation: OpenLab Gene and Cell Technologies, Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: Y O
authors.initials: YO
authors.lastname: Mukhamedshina
authors.affiliation: Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, Kazan, Russia.
authors.forename: G F
authors.initials: GF
authors.lastname: Shaymardanova
authors.affiliation: OpenLab Gene and Cell Technologies, Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: Е Е
authors.initials: ЕЕ
authors.lastname: Garanina
authors.affiliation: OpenLab Gene and Cell Technologies, Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: I I
authors.initials: II
authors.lastname: Salafutdinov
authors.affiliation: OpenLab Gene and Cell Technologies, Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: А А
authors.initials: АА
authors.lastname: Rizvanov
authors.affiliation: Department of Hystology, Kazan State Medical University, Kazan, Russia.
authors.forename: R R
authors.initials: RR
authors.lastname: Islamov
authors.affiliation: Department of Hystology, Kazan State Medical University, Kazan, Russia.
authors.forename: Y A
authors.initials: YA
authors.lastname: Chelyshev
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D017630:Connexins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008124:Locomotion / Q000502:physiology; D008297:Male; D018993:Myelin P0 Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020127:Recovery of Function; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000235:genetics / Q000628:therapy*; D018709:Statistics, Nonparametric
chemical_list: D051401:Aquaporin 4; D017630:Connexins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D018993:Myelin P0 Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha