Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects
Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects
复制标题
间充质干细胞来源的外泌体通过抗氧化和抗炎作用改善椎间盘退变
DOI：
10.1016/j.freeradbiomed.2019.07.026
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发表时间：
2019-11-01
影响因子：
7.4
通讯作者：
Chen, Pengfei
中科院分区：
文献类型：
--
作者：
Xia, Chen;Zeng, Zhongyou;Chen, Pengfei
过度氧化应激和炎症是椎间盘退行性变(IVDD)发生的关键早期事件。Nacht、LRR和PYD结构域包含蛋白3(NLRP3)的炎性小体被认为是氧化应激和炎症反应的主要来源，因此是IVDD的一个有吸引力的治疗靶点。然而，目前还没有关于使用间充质干细胞(MSC)来源的外切体来降低IVDD治疗中NLRP3炎症体表达的报道。本研究旨在探讨外切体作为IVDD治疗药物的疗效。我们首先制造并评估了外切体的特性。然后，我们研究了外切体在H_2O_2诱导的髓核细胞炎症中的作用。第三，我们测试了外切体在过氧化氢诱导的ROS产生和线粒体功能障碍方面的功能。最后，利用兔IVDD模型研究了Exosome对IVDD的治疗作用。结果表明，Exosome通过抑制炎症介质和NLRP3炎性小体的激活，在病理性NP细胞中发挥抗炎作用。此外，还表明外切体可能向NP细胞提供线粒体蛋白，这种补充可以恢复受损的线粒体。此外，在兔IVDD模型中，外切体显著阻止了退行性变化的进展。我们的结果证实了NLRP3炎性小体是IVDD治疗的有效靶点，注射外切体可能是一种有前途的治疗策略。
Excessive oxidative stress and inflammation are the key early events in the development of intervertebral disc degeneration (IVDD). The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome has been identified as the major source of oxidative stress and the inflammatory responses and thus is an attractive therapeutic target for IVDD. However, currently, there are no reports on the use of mesenchymal stem cell (MSC)-derived exosomes to reduce NLRP3 inflammasome expression for IVDD treatment. The present study aimed to investigate the therapeutic effect of exosomes for use as IVDD therapeutics. We first manufactured and evaluated the characteristics of exosomes. Then, we investigated the effects of exosomes on H2O2-induced nucleus pulposus (NP) cell inflammation. Third, we tested the function of exosomes with respect to H2O2-induced ROS production and mitochondrial dysfunction. Finally, the therapeutic effect of exosomes on IVDD was investigated using a rabbit IVDD model. Results showed that exosomes play an anti-inflammatory role in pathological NP cells by suppressing inflammatory mediators and NLRP3 inflammasome activation. Moreover, it was suggested that exosomes might supply mitochondrial proteins to NP cells, and that the damaged mitochondria could be restored with this supplement. Further, in the rabbit IVDD model, exosomes significantly prevented the progression of degenerative changes. Our results confirmed that the NLRP3 inflammasome is an effective target for IVDD treatment and that the injection of exosomes could be a promising therapeutic strategy.