A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia.
Molecules. 2018 Mar 19;23(3):687. doi: 10.3390/molecules23030687.
A recently discovered key role of reactive oxygen species (ROS) in mitochondrial traffic has opened a wide alley for studying the interactions between cells, including stem cells. Since its discovery in 2006, intercellular mitochondria transport has been intensively studied in different cellular models as a basis for cell therapy, since the potential of replacing malfunctioning organelles appears to be very promising. In this study, we explored the transfer of mitochondria from multipotent mesenchymal stem cells (MMSC) to neural cells and analyzed its efficacy under normal conditions and upon induction of mitochondrial damage. We found that mitochondria were transferred from the MMSC to astrocytes in a more efficient manner when the astrocytes were exposed to ischemic damage associated with elevated ROS levels. Such transport of mitochondria restored the bioenergetics of the recipient cells and stimulated their proliferation. The introduction of MMSC with overexpressed Miro1 in animals that had undergone an experimental stroke led to significantly improved recovery of neurological functions. Our data suggest that mitochondrial impairment in differentiated cells can be compensated by receiving healthy mitochondria from MMSC. We demonstrate a key role of Miro1, which promotes the mitochondrial transfer from MMSC and suggest that the genetic modification of stem cells can improve the therapies for the injured brain.
最近发现活性氧 (ROS) 在线粒体运输中的关键作用，为研究细胞间相互作用，包括干细胞，开辟了广阔的途径。自 2006 年发现以来，细胞间线粒体运输已在不同的细胞模型中被深入研究，作为细胞治疗的基础，因为替换功能失调细胞器的潜力似乎非常有前景。在这项研究中，我们探索了多能间充质干细胞 (MMSC) 向神经细胞转移线粒体，并在正常条件和诱导线粒体损伤下分析其功效。我们发现，当星形胶质细胞暴露于与 ROS 水平升高相关的缺血性损伤时，MMSC 向星形胶质细胞转移线粒体的效率更高。这种线粒体的转移恢复了受体细胞的生物能量，并刺激了它们的增殖。在经历实验性中风的动物中引入过表达 Miro1 的 MMSC 导致神经功能恢复显著改善。我们的数据表明，分化细胞中线粒体的损伤可以通过接收来自 MMSC 的健康线粒体得到补偿。我们证明了 Miro1 的关键作用，它促进了 MMSC 中线粒体的转移，并表明干细胞的基因修饰可以改善对受损大脑的治疗。
