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Brain Res Bull ; 132: 44-52, 2017 06.
Article in English | MEDLINE | ID: mdl-28529158

ABSTRACT

Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs). Following the induction of SCI, serial assessment of cord regeneration was performed, including morphometric analysis of gray and white matters, electrophysiology and behavioral test. The therapeutic gene combinations VEGF+GDNF+NCAM and VEGF+ANG+NCAM had positive outcomes on spinal cord regeneration, with enhanced recovery seen by the cell-based approach when compared to direct gene therapy. The efficacy of the genes and the delivery methods are discussed in this paper, recommending their potential use in SCI.


Subject(s)
CD56 Antigen/genetics , Genetic Therapy/methods , Glial Cell Line-Derived Neurotrophic Factor/genetics , Ribonuclease, Pancreatic/genetics , Spinal Cord Injuries/therapy , Vascular Endothelial Growth Factor A/genetics , Adenoviridae/genetics , Animals , CD56 Antigen/metabolism , Cord Blood Stem Cell Transplantation , Disease Models, Animal , Escherichia coli , Female , Fetal Blood/cytology , Genetic Vectors , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , HEK293 Cells , Humans , Injections, Spinal , Rats, Wistar , Ribonuclease, Pancreatic/metabolism , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Spinal Cord Regeneration/physiology , Transduction, Genetic , Vascular Endothelial Growth Factor A/metabolism
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