Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier

Frontiers in Neuroscience

卷:13

Yanhui Lu¹  Ruiyi Zhang¹  Kaimin Wu²  Yaobing Yao²  Yanjie Jia²  Ranran Duan²  Lulu Wen²  Yanfei Li²  Yan Zhou³ 

[1] Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China;

[2] Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;

[3] Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;

关键词: extracellular vesicles;    bone mesenchymal stromal cells;    spinal cord injury;    blood spinal cord barrier;    pericytes;    migration;   

DOI  :  10.3389/fnins.2019.00209

来源: DOAJ

【 摘 要 】

Mesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). However, there are several obstacles that need to be overcome before MSCs can be considered for clinical application, such as failure of MSCs to reach the spinal cord lesion core and possible tumor formation. Recent studies have suggested that MSC treatment is beneficial owing to paracrine-secreted factors. Extracellular vesicles are considered to be some of the most valuable paracrine molecules. However, the therapeutic mechanism of extracellular vesicles on spinal cord injury has not been studied clearly. Therefore, our study investigated the effect of systemic administration of extracellular vesicles on the loss of motor function after SCI and examined the potential mechanisms underlying their effects. Disruption of the blood-spinal cord barrier (BSCB) is a crucial factor that can be detrimental to motor function recovery. Pericytes are an important component of the neurovascular unit, and play a pivotal role in maintaining the structural integrity of the BSCB. Our study demonstrated that administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function compared with the administration of BMSC-EV free culture media (EV-free CM). Besides, the BSCB was attenuated and pericyte coverage was significantly decreased in vivo. Furthermore, we found that exosomes reduced pericyte migration via downregulation of NF-κB p65 signaling, with a consequent decrease in the permeability of the BSCB. In summary, we identified that extracellular vesicles treatment suppressed the migration of pericytes and further improved the integrity of the BSCB via NF-κB p65 signaling in pericytes. Our data suggest that extracellular vesicles may serve as a promising treatment strategy for SCI.

【 授权许可】

Unknown