title: Assessment of Glial Scar, Tissue Sparing, Behavioral Recovery and Axonal Regeneration following Acute Transplantation of Genetically Modified Human Umbilical Cord Blood Cells in a Rat Model of Spinal Cord Contusion.
abstract: OBJECTIVE
  This study investigated the potential for protective effects of human umbilical cord blood mononuclear cells (UCB-MCs) genetically modified with the VEGF and GNDF genes on contusion spinal cord injury (SCI) in rats. An adenoviral vector was constructed for targeted delivery of VEGF and GDNF to UCB-MCs. Using a rat contusion SCI model we examined the efficacy of the construct on tissue sparing, glial scar severity, the extent of axonal regeneration, recovery of motor function, and analyzed the expression of the recombinant genes VEGF and GNDF in vitro and in vivo.
  
  
  RESULTS
  Transplantation of UCB-MCs transduced with adenoviral vectors expressing VEGF and GDNF at the site of SCI induced tissue sparing, behavioral recovery and axonal regeneration comparing to the other constructs tested. The adenovirus encoding VEGF and GDNF for transduction of UCB-MCs was shown to be an effective and stable vehicle for these cells in vivo following the transplantation into the contused spinal cord.
  
  
  CONCLUSIONS
  Our results show that a gene delivery using UCB-MCs-expressing VEGF and GNDF genes improved both structural and functional parameters after SCI. Further histological and behavioral studies, especially at later time points, in animals with SCI after transplantation of genetically modified UCB-MCs (overexpressing VEGF and GDNF genes) will provide additional insight into therapeutic potential of such cells.
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Tatarstan, Kazan, Russia.
authors.forename: Yana O
authors.initials: YO
authors.lastname: Mukhamedshina
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Tatarstan, Kazan, Russia.
authors.forename: Ekaterina E
authors.initials: EE
authors.lastname: Garanina
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Tatarstan, Kazan, Russia.
authors.forename: Galina A
authors.initials: GA
authors.lastname: Masgutova
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Tatarstan, Kazan, Russia.
authors.forename: Luisa R
authors.initials: LR
authors.lastname: Galieva
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Tatarstan, Kazan, Russia.
authors.forename: Elvira R
authors.initials: ER
authors.lastname: Sanatova
authors.affiliation: Department of histology, Kazan State Medical University, Tatarstan, Kazan, Russia.
authors.forename: Yurii A
authors.initials: YA
authors.lastname: Chelyshev
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Tatarstan, Kazan, Russia.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Rizvanov
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002921:Cicatrix; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000637:transplantation*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins