Islamov Rustem Robertovich, Izmailov Andrey Alexandrovich, Sokolov Mikhail Evgenyevich, Fadeev Philip Olegovich, Bashirov Farid Vagizovich, Eremeev Anton Alexandrovich, Shaymardanova Gulnara Ferdinantovna, Shmarov Maxim Michaylovich, Naroditskiy Boris Savelyevich, Chelyshev Yuri Alexandrovich, Lavrov Igor Aleksandrovich, Palotás András
Kazan State Medical University, Kazan, Russia.
Kazan Federal University, Kazan, Russia.
Brain Res Bull. 2017 Jun;132:44-52. doi: 10.1016/j.brainresbull.2017.05.005. Epub 2017 May 18.
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.
目前脊髓损伤（SCI）的治疗选择有限。最有前景的创新方法之一包括基因治疗，然而迄今为止尚未有单个基因显示出具有临床相关性。本研究调查了血管内皮生长因子（VEGF）、胶质细胞源性神经营养因子（GDNF）、血管生成素（ANG）和神经元细胞黏附分子（NCAM）的各种组合对大鼠的疗效。通过腺病毒载体或使用基因改造的人脐带血单个核细胞（hUCBMCs）鞘内注射多种治疗基因。在诱导脊髓损伤后，对脊髓再生进行系列评估，包括灰质和白质的形态计量分析、电生理学和行为测试。治疗基因组合VEGF+GDNF+NCAM和VEGF+ANG+NCAM对脊髓再生有积极效果，与直接基因治疗相比，基于细胞的方法显示出更好的恢复效果。本文讨论了基因和递送方法的疗效，推荐它们在脊髓损伤中的潜在应用。
