Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

作     者：Zeyan Liang Zhelun Yang Haishu Xie Jian Rao Xiongjie Xu Yike Lin Chunhua Wang Chunmei Chen Zeyan Liang;Zhelun Yang;Haishu Xie;Jian Rao;Xiongjie Xu;Yike Lin;Chunhua Wang;Chunmei Chen

作者机构：Department of NeurosurgeryFujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Neurosurgical InstituteFuzhouFujian ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2024年第19卷第10期

页      面：2259-2269页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the Fujian Minimally Invasive Medical Center Foundation,No.2128100514(to CC,CW,HX) the Natural Science Foundation of Fujian Province,No.2023J01640(to CC,CW,ZL,HX)。 

主　　题：bone marrow mesenchymal stem cells hypoxia preconditioning interleukin-1 receptor-associated kinase 1 macrophages mesenchymal stem cells small extracellular vesicles spinal cord injury 

摘      要：Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.