Extracellular Vesicles Derived from Epidural Fat-Mesenchymal Stem Cells Attenuate NLRP3 Inflammasome Activation and Improve Functional Recovery After Spinal Cord Injury
Extracellular Vesicles Derived from Epidural Fat-Mesenchymal Stem Cells Attenuate NLRP3 Inflammasome Activation and Improve Functional Recovery After Spinal Cord Injury
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硬膜外脂肪间充质干细胞衍生的细胞外囊泡可减弱 NLRP3 炎性体激活并改善脊髓损伤后的功能恢复
DOI：
10.1007/s11064-019-02950-x
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发表时间：
2020-01-17
影响因子：
4.4
通讯作者：
Lin, Fei-Yue
中科院分区：
文献类型：
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作者：
Huang, Jiang-Hu;Fu, Chun-Hui;Lin, Fei-Yue
脊髓损伤（SCI）是一种毁灭性事件，导致高死亡率和发病率。最近，核苷酸结合域样受体蛋白 3 (NLRP3) 炎性体已被证明在 SCI 的第二损伤阶段发挥着关键作用。在本研究中，我们旨在探讨硬膜外脂肪（EF）-间充质干细胞（MSC）来源的细胞外囊泡治疗 SCI 的效果和潜在分子机制。 96只Sprague-Dawley大鼠用于本研究，随机分为四组：假手术组、SCI组、SCI + 生理盐水组、SCI + 细胞外囊泡组。 Basso-Beattie-Bresnahan (BBB) 评分用于评估神经功能恢复情况。甲酚紫染色评价 EF-MSCs-细胞外囊泡对 SCI 后病灶体积的保护作用。通过 ELISA、免疫组织化学测定、TUNEL 测定和蛋白质印迹来研究潜在的分子机制。我们的结果表明，通过尾静脉注射 EF-MSCs-细胞外囊泡可改善神经功能恢复并减少 SCI 后的病变体积。全身给予EF-MSCs-细胞外囊泡可显着抑制NLRP3炎症小体活化并减少炎症细胞因子的表达。此外，SCI后EF-MSCs-细胞外囊泡处理促凋亡蛋白Bax的表达水平降低，抗凋亡蛋白Bcl-2表达水平上调。总之，在本研究中，我们首次证明EF-MSCs-细胞外囊泡可以改善SCI后神经功能的恢复，其潜在的分子机制可能部分是通过抑制NLRP3炎症小体的激活。
Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effect and underlying molecular mechanisms of extracellular vesicles derived from epidural fat (EF)- mesenchymal stem cells (MSCs) for the treatment of SCI. Ninety-six Sprague–Dawley rats were used for current study and randomly divided into four groups: sham group, SCI group, SCI + Saline group, SCI + Extracellular vesicles group. Basso‐Beattie‐Bresnahan (BBB) scores was applied to evaluate the neurological functional recovery. Cresyl violet–stained was conducted evaluate the protective effect of EF-MSCs-Extracellular vesicles on lesion volume after SCI. ELISA, immunohistochemistry assay, TUNEL assay and western blotting were conducted to investigate the underlying molecular mechanisms. Our results demonstrated that the administration of EF-MSCs-Extracellular vesicles via tail vein injection improved neurological functional recovery and reduced the lesion volume after SCI. And systemic administration of EF-MSCs-Extracellular vesicles significantly inhibited NLRP3 inflammasome activation and reduced the expression of inflammatory cytokines. Additionally, the expression levels of proapoptotic protein Bax was decreased and antiapoptotic Bcl-2 was upregulated with the treatment of EF-MSCs-Extracellular vesicles after SCI. In summary, in current study, we demonstrated for the first time that the EF-MSCs-Extracellular vesicles can improve neurological functional recovery after SCI, and the underlying molecular mechanisms may partly through the inhibition of NLRP3 inflammasome activation.