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脊髓损伤的新疗法：自体基因富集白细胞浓缩物联合硬膜外电刺激。

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation.

机构信息

Department of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia.

The National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia.

出版信息

Cells. 2022 Jan 2;11(1):144. doi: 10.3390/cells11010144.

DOI:10.3390/cells11010144
PMID:35011706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8750549/
Abstract

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

摘要

脊髓损伤 (SCI) 治疗的当代策略旨在结合多种方法来控制神经退行性病变的发病机制并刺激神经再生。在这项研究中，使用自体富含转染血管内皮生长因子 (VEGF)、胶质细胞源性神经营养因子 (GDNF) 和神经细胞黏附分子 (NCAM) 的浓缩白细胞，并结合超损伤和损伤下硬膜外电刺激 (EES) 的新型再生方法在类似于人类形态生理比例的小型猪上进行了测试。与对照动物相比，对接受治疗的小型猪中度挫伤损伤后脊髓恢复进行的综合分析表明：行为和关节运动学表现更好，肌电图特征恢复，以及与细胞存活、突触蛋白表达和损伤上下胶质重排相关的选定免疫组织化学特征得到改善。这些结果首次证明了静脉内输注自体基因丰富的浓缩白细胞产生的重组分子刺激神经再生，并结合跨损伤多部位 EES 的神经调节对小型猪创伤后脊髓恢复的积极影响，并表明这种新型再生疗法对 SCI 患者具有很高的转化潜力。

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