title: A pilot study of cell-mediated gene therapy for spinal cord injury in mini pigs.
abstract: Currently, in clinical practice there is no efficient way to overcome the sequences of neurodegeneration after spinal cord traumatic injury. Using a new experimental model of spinal cord contusion injury on miniature pigs, we proposed to deliver therapeutic genes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) to the damaged area, using umbilical cord blood mononuclear cells (UCBC). In this study, genetically engineered UCBC (2×106cells in 200 ml of saline) were injected intrathecally to mini-pigs 10days after SCI. Control and experimental mini pigs were observed for 60days after surgery. Histological, electrophysiological, and clinical evaluation demonstrated significant improvement in animal treated with genetically engineered UCBCs. Difference in recovery of the somatosensory evoked potentials and in histological findings in control and treated animals support the positive effect of the gene-cell constriction for recovery after spinal cord injury. Results of this study suggest that transplantation of UCBCs simultaneously transduced with three recombinant adenoviruses Ad5-VEGF, Ad5-GDNF and Ad5-NCAM represent a novel potentially successful approach for treatment of spinal cord injury.
authors.affiliation: Kazan State Medical University, Kazan, Russia.
authors.forename: Rustem Robertovich
authors.initials: RR
authors.lastname: Islamov
authors.affiliation: Kazan State Medical University, Kazan, Russia; Kazan Federal University, Kazan, Russia.
authors.forename: Mikhail Evgenyevich
authors.initials: ME
authors.lastname: Sokolov
authors.affiliation: Kazan State Medical University, Kazan, Russia.
authors.forename: Farid Vagizovich
authors.initials: FV
authors.lastname: Bashirov
authors.affiliation: Kazan State Medical University, Kazan, Russia; Kazan Federal University, Kazan, Russia.
authors.forename: Filip Olegovich
authors.initials: FO
authors.lastname: Fadeev
authors.affiliation: Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Maxim Michaylovich
authors.initials: MM
authors.lastname: Shmarov
authors.affiliation: Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Boris Savelyevich
authors.initials: BS
authors.lastname: Naroditskiy
authors.affiliation: Kazan State Medical University, Kazan, Russia.
authors.forename: Tatyana Vyacheslavovna
authors.initials: TV
authors.lastname: Povysheva
authors.affiliation: Kazan State Medical University, Kazan, Russia.
authors.forename: Gulnara Ferdinantovna
authors.initials: GF
authors.lastname: Shaymardanova
authors.affiliation: Kazan State Medical Academy, Kazan, Russia.
authors.forename: Radik Albertovich
authors.initials: RA
authors.lastname: Yakupov
authors.affiliation: Kazan State Medical University, Kazan, Russia; Kazan Federal University, Kazan, Russia.
authors.forename: Yuri Aleksandrovich
authors.initials: YA
authors.lastname: Chelyshev
authors.affiliation: Kazan Federal University, Kazan, Russia; Departments of Neurologic Surgery and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States. Electronic address: lavrov.igor@mayo.edu.
authors.forename: Igor Aleksandrovich
authors.initials: IA
authors.lastname: Lavrov
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D010865:Pilot Projects; D020127:Recovery of Function; D013119:Spinal Cord Injuries; D013552:Swine; D013556:Swine, Miniature; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D019006:Neural Cell Adhesion Molecules; D042461:Vascular Endothelial Growth Factor A
keywords: Adenoviral vector; Cell-mediated gene therapy; Glial cell-derived neurotrophic factor (GDNF); Human umbilical cord blood mononuclear cell; Mini pigs; Neural cell adhesion molecule (NCAM); Spinal cord injury; Vascular endothelial growth factor (VEGF)