Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage.
Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage.
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间充质干细胞的线粒体转移有效保护角膜上皮细胞免受线粒体损伤。
DOI：
10.1038/cddis.2016.358
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发表时间：
2016-11-10
影响因子：
9
通讯作者：
Lian Q
中科院分区：
文献类型：
--
作者：
Jiang D;Gao F;Zhang Y;Wong DS;Li Q;Tse HF;Xu G;Yu Z;Lian Q
最近的研究表明，间充质干细胞(MSCs)可以向呼吸道上皮细胞捐献线粒体，修复肺损伤中的线粒体损伤。我们试图确定MSCs是否可以捐赠线粒体并保护角膜免受氧化应激诱导的线粒体功能障碍。共培养的MSCs和角膜上皮细胞(CECs)表明，鱼藤酮(Rot)诱导的氧化应激提高了线粒体从MSCs到CECs的转移效率。有效的线粒体转移与MSCs和CECs之间形成隧道纳米管(TNTs)的增加有关，TNTs是允许细胞间直接通信的管状连接。用Transwell培养系统分离MSCs和CECs，发现当CECs暴露于Rot攻击时，没有线粒体从MSCs转移到CECs，线粒体功能受损。有无线粒体转移的MSCs来源的CECs显示出明显的存活能力和线粒体耗氧率。从机制上讲，TnT形成的CEC丝状孢子突起增加与氧化炎症激活的NFκB/肿瘤坏死因子αip2信号通路有关，该信号通路可被活性氧种清除剂N-乙酰半胱氨酸(N-乙酰半胱氨酸)处理减弱。此外，在脱细胞猪角膜支架上生长的MSCs被移植到碱损伤的兔眼模型中。健康的MSC支架移植后，角膜伤口愈合明显增强。在角膜上皮细胞中检测到转移的线粒体。总之，骨髓间充质干细胞的线粒体转移为角膜提供了新的保护措施，以对抗氧化应激诱导的线粒体损伤。这一治疗策略可能被证明与广泛的线粒体疾病相关。
Recent studies have demonstrated that mesenchymal stem cells (MSCs) can donate mitochondria to airway epithelial cells and rescue mitochondrial damage in lung injury. We sought to determine whether MSCs could donate mitochondria and protect against oxidative stress-induced mitochondrial dysfunction in the cornea. Co-culturing of MSCs and corneal epithelial cells (CECs) indicated that the efficiency of mitochondrial transfer from MSCs to CECs was enhanced by Rotenone (Rot)-induced oxidative stress. The efficient mitochondrial transfer was associated with increased formation of tunneling nanotubes (TNTs) between MSCs and CECs, tubular connections that allowed direct intercellular communication. Separation of MSCs and CECs by a transwell culture system revealed no mitochiondrial transfer from MSCs to CECs and mitochondrial function was impaired when CECs were exposed to Rot challenge. CECs with or without mitochondrial transfer from MSCs displayed a distinct survival capacity and mitochondrial oxygen consumption rate. Mechanistically, increased filopodia outgrowth in CECs for TNT formation was associated with oxidative inflammation-activated NFκB/TNFαip2 signaling pathways that could be attenuated by reactive oxygen species scavenger N-acetylcysteine (NAC) treatment. Furthermore, MSCs grown on a decellularized porcine corneal scaffold were transplanted onto an alkali-injured eye in a rabbit model. Enhanced corneal wound healing was evident following healthy MSC scaffold transplantation. And transferred mitochondria was detected in corneal epithelium. In conclusion, mitochondrial transfer from MSCs provides novel protection for the cornea against oxidative stress-induced mitochondrial damage. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.