Role Of Exosomes Derived From Bone Marrow Mesenchymal Stem Cells In Brain Injury After Cerebral Ischemia

ObjectiveBone marrow mesenchymal stem cells(MSC)are equipotent stem cells with strong immunosuppressive properties,which have a very strong ability to secrete exosomes.MSC-Exo can promote the information transmission between cells through different ways,and govern the body’s immune response by antigen presentation.IL-33 can regulate inflammation by binding to its specific receptor in ST2.Therefore,we will study the role of MSC-Exo in the brain injury after ischemic stroke,and further explore the effect of MSC-Exo on IL-33 / ST2 signaling pathway.Methods In animal experiments,the middle cerebral artery occlusion(MCAO)model of mice was established.MSC-Exo was injected into the tail of mice to explore its protective effect on brain injury after cerebral ischemia.At the same time,IL-33 recombinant protein(200 μg/kg)was put into the tail vein of mice as a positive control.MSC-Exo was marked by TSG101,Alix and CD63.The surface of exosomes was respected by atomic force microscopy(AFM)and transmission electron microscopy(SEM).The PKH26 labeled MSC-Exo was utilized to observe whether it passed through the blood-brain barrier(BBB).The volume of cerebral infarction was observed by TTC staining,the expression of IL-33 in neurons was detected by Western blot,and the expression of IL-33 in neurons was detected by immunofluorescence.Results The level of IL-33 protein increased significantly at 24 h and 48 h reperfusion after 1 h MCAO,and decreased at 72 h reperfusion.The expression of IL-33 was up-regulated after administration of recombinant IL-33 protein.TTC and neurological function evaluation showed that recombinant IL-33 has brain protective effects after 1 h MCAO and 24 h reperfusion.It also finds that MSC-Exo treatment enhanced the level of IL-33 protein.Moreover,MSC-Exo showed similar neuroprotective effect as recombinant IL-33.It was noted that MSC-Exo could prevent neuron injury induced by cerebral ischemia by activating IL-33/ST2 signaling pathway.Conclusions MSC-Exo has a effect on cerebral ischemia injury.MSC-Exo treatment has a effect after cerebral ischemia by activating IL-33/ST2 signaling pathway.MSC-Exo may be a possible therapeutic strategy in the treatment of acute ischemic stroke.