治疗神经性疼痛的新方法:成纤维细胞生长因子 1 基因转染脂肪间充质干细胞。
New approach for the treatment of neuropathic pain: Fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells.
机构信息
Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
出版信息
Eur J Pain. 2018 Feb;22(2):295-310. doi: 10.1002/ejp.1119. Epub 2017 Sep 26.
BACKGROUND
Neuropathic pain triggered by peripheral nerve lesion is extremely difficult to manage with current approaches, hence the importance of exploring therapeutic alternatives.
METHODS
We have analysed adipose-derived mesenchymal stem cells (AD-MSCs) and fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells (AD-MSCs ) on chronic constriction injury (CCI). The mechanical and thermal hypersensitivity were assessed using the von Frey filament, radiant heat and acetone drop tests. Histopathological and apoptotic changes and the level of FGF1, GFAP and TNFα proteins were assessed in the lumbar portion (L4-L6). Moreover, AD-MSCs were labelled with Tc -HMPAO and isolated organ counting were performed upon AD-MSCs administration.
RESULTS
Administration of AD-MSCs attenuated the CCI-induced mechanical and thermal hypersensitivity. Spinal structural alterations and apoptosis were decreased in the AD-MSCs group. The injection of either phosphate-buffered saline or normal NIH3T3 fibroblasts could not attenuate the behavioural symptoms of neuropathic pain. Increased genetically engineered cells were counted in the injured sciatic nerve and the elevated levels of FGF1 were detected in the spinal tissue. Stem cell therapy lead to decrement the level of the CCI-induced TNF-α and GFAP expression.
CONCLUSION
The intravenous administration of AD-MSCs could be considered as a potential remedy for the management of neuropathic pain.
SIGNIFICANCE
AD-MSCs attenuated the CCI-induced mechanical and thermal hypersensitivity. Spinal structural alterations and apoptosis were significantly decreased in the AD-MSCs group. Elevated levels of FGF1 were detected in the spinal tissue.
背景
外周神经损伤引发的神经性疼痛目前很难通过现有方法进行治疗,因此探索治疗方法非常重要。
方法
我们分析了脂肪间充质干细胞(AD-MSCs)和成纤维细胞生长因子 1 基因转染脂肪间充质干细胞(AD-MSCs)对慢性缩窄性损伤(CCI)的影响。使用 von Frey 细丝、辐射热和丙酮滴试验评估机械和热感觉过敏。在 L4-L6 腰椎部分评估组织病理学和细胞凋亡变化以及 FGF1、GFAP 和 TNFα 蛋白水平。此外,Tc-HMPAO 标记 AD-MSCs,进行 AD-MSCs 给药后的分离器官计数。
结果
AD-MSCs 给药可减轻 CCI 引起的机械和热感觉过敏。AD-MSCs 组脊髓结构改变和细胞凋亡减少。注射磷酸盐缓冲液或正常 NIH3T3 成纤维细胞均不能减轻神经性疼痛的行为症状。在损伤的坐骨神经中计数到更多的基因工程细胞,在脊髓组织中检测到 FGF1 水平升高。干细胞治疗可降低 CCI 诱导的 TNF-α和 GFAP 表达水平。
结论
静脉注射 AD-MSCs 可被视为治疗神经性疼痛的一种潜在方法。
意义
AD-MSCs 减轻了 CCI 引起的机械和热感觉过敏。AD-MSCs 组脊髓结构改变和细胞凋亡明显减少。在脊髓组织中检测到 FGF1 水平升高。