Mesenchymal stem cell derived EVs mediate neuroprotection after spinal cord injury in rats via the microRNA-21-5p/FasL gene axis
Mesenchymal stem cell derived EVs mediate neuroprotection after spinal cord injury in rats via the microRNA-21-5p/FasL gene axis
复制标题
间充质干细胞衍生的 EV 通过 microRNA-21-5p/FasL 基因轴介导大鼠脊髓损伤后的神经保护
DOI：
10.1016/j.biopha.2019.108818
复制
发表时间：
2019-07-01
影响因子：
7.5
通讯作者：
Wang, Dachuan
中科院分区：
文献类型：
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作者：
Zhou, Xin;Chu, Xili;Wang, Dachuan
脊髓损伤（SCI）是一种较为常见的运动系统损伤。脊髓损伤患者会出现不同程度的截瘫和四肢瘫痪，严重影响其生活质量的同时，也给家庭和整个社会带来了沉重的负担。这种疾病的确切致病机制尚不清楚，目前也没有具体的治疗方法。最近的研究发现，来自细胞外囊泡（EVs）的间充质干细胞（MSCs）可以减少脊髓损伤后的细胞凋亡、炎症和促进血管生成。然而，电动汽车发挥这些作用的机制尚未确定，这表明有必要进一步研究。在本研究中，我们报告了mscs - ev治疗可显著改善脊髓损伤大鼠模型的功能恢复，减轻病变大小和细胞凋亡。这些间充质干细胞- ev被发现指向脊髓损伤部位，主要结合到脊髓损伤部位的神经元中。应用Tandem Mass Tags定量蛋白质组学比较SCI和mscs - ev处理后的蛋白质变化。共鉴定出883种差异蛋白，其中许多与细胞凋亡和炎症有关。随后，我们使用qRT-PCR检测了mscs - ev中miRNA的含量，结果发现miR-21-5p是这些mscs - ev中表达量最高的miRNA之一。此外，miR-21-5p在mscs - ev中的抑制显著逆转了mscs - ev对运动功能和凋亡的有益作用，这一作用与调节FasL表达有关。这些数据表明，调节mscs - ev的miR-21-5p/FasL基因轴可能作为一种有希望的策略，用于临床治疗SCI和其他神经系统疾病。
Spinal cord injury (SCI) represents a relatively common type of motor system trauma. While the SCI patient will experience varying degrees of paraplegia and quadriplegia, which severely affects their quality of life, a heavy burden is also placed on the family and society as a whole. The exact pathogenic mechanisms underlying this condition remain unknown and no specific treatments are currently available. Findings from recent studies have shown that mesenchymal stem cells (MSCs), derived from extracellular vesicles (EVs) can reduce apoptosis, inflammation and promote angiogenesis after SCI. However, the mechanisms through which EVs exert these effects have yet to be identified, indicating the necessity for further investigation. In the present study, we report that treatment with MSCs-EVs significantly improved functional recovery and attenuated lesion size and apoptosis in a rat model of SCI. These MSCs-EVs were found to be directed to the spinal injury site and mainly incorporated into neurons within the lesioned site of the spinal cord. Tandem Mass Tags quantitative proteomics was applied to compare protein changes after SCI and MSCs-EVs treatment. A total of 883 differential proteins were identified, many of which being associated with apoptosis and inflammation. Subsequently, miRNA contents of MSCs-EVs were determined using qRT-PCR, with the result that miR-21-5p was one of the most highly expressed miRNA in these MSCs-EVs. Moreover, inhibition of miR-21-5p in MSCs-EVs significantly reversed the beneficial effects of MSCs-EVs on motor function and apoptosis, an effect which was associated with modulating FasL expression. The data suggest that modulation of the MSCs-EVs miR-21-5p/FasL gene axis may serve as a promising strategy for clinical treatment of SCI and other neurological diseases.