Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis  

作　　者：Yan Zhou Lu-Lu Wen Yan-Fei Li Kai-Min Wu Ran-Ran Duan Yao-Bing Yao Li-Jun Jing Zhe Gong Jun-Fang Teng Yan-Jie Jia 

机构地区：[1]Department of Radiology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan Province,China [2]Department of Neurology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan Province,China

出　　处：《Neural Regeneration Research》2022年第1期194-202,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of ChinaNo.U1604170(to YJJ)。

摘　　要：Mesenchymal stem cell(MSC)transplantation is a promising treatment strategy for spinal cord injury,but immunological rejection and possible tumor formation limit its application.The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors.Exosomes are essential for the secretion of these paracrine effectors.Bone marrow mesenchymal stem cell-derived exosomes(BMSC-EXOs)can be substituted for BMSCs in cell transplantation.However,the underlying mechanisms remain unclear.In this study,a rat model of T10 spinal cord injury was established using the impact method.Then,30 minutes and 1 day after spinal cord injury,the rats were administered 200μL exosomes via the tail vein(200μg/mL;approximately 1×106 BMSCs).Treatment with BMSC-EXOs greatly reduced neuronal cell death,improved myelin arrangement and reduced myelin loss,increased pericyte/endothelial cell coverage on the vascular wall,decreased bloodspinal cord barrier leakage,reduced caspase 1 expression,inhibited interleukin-1βrelease,and accelerated locomotor functional recovery in rats with spinal cord injury.In the cell culture experiment,pericytes were treated with interferon-γand tumor necrosis factor-α.Then,Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells,and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro.Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate.These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity,thereby promoting the survival of neurons and the extension of nerve fibers,and ultimately improving motor function in rats with spinal cord injury.All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16,2019.

关 键 词：blood-spinal cord barrier EDEMA EXOSOME PERICYTE NOD1 pro-caspase 1 PYROPTOSIS spinal cord injury 

分 类 号：R456[医药卫生—治疗学] R745.4[医药卫生—临床医学]