Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury

Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair.However,the underlying molecular mechanism remains unclear.In this study,we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation.Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype,inhibited the expression of proinflammatory cytokines,and increased the expression of anti-inflammatory cytokines.Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury,inhibited neuroinflammation,and promoted the transformation of microglia to the anti-inflammatory phenotype.We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process.Finally,we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection.We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype.The interleukin 10/STAT3 pathway was activated during this process.These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.

Calcitonin gene related peptide modified mesenchymal stem cells reduce restenosis after carotid balloon injury in rats

This work aimed to investigate the effects of calcitonin gene-related peptide(CGRP)-modified mesenchymal stem cells(MSCs)on vascular stenosis in carotid balloon-injured rats.The CGRP gene labeled with EGFP was transfected into bone marrow MSCs,and CGRP protein expression in MSCs was confirmed by immunofluorescence assays.A rat carotid balloon injury model was established using a surgicalmethod.CGRP-modifiedMSCs were orthotopically transplanted into the injured area of the rats.At 28 days after cell transplantation,EGFP and CD31 expression was detected by immunofluorescence staining.Hematoxylin-eosin(H&E)staining was used to detect the intima/media area of the injured carotid artery stenosis site,and the expression of proliferating cell nuclear antigen(PCNA)was detected by immunohistochemistry.MSCs from rat bone marrow positively expressed CD29 and negatively expressed CD45.In vivo immunofluorescence staining showed that EGFP expression was significantly increased at the vascular injury site of rats transplanted with MSC_CGRP compared with the control group on the 28th day after cell transplantation and that the damaged vessels exhibited continuous CD31 expression.H&E staining showed that the vascular intimal proliferation area of rats transplanted with MSC_CGRP was significantly reduced compared with that of other groups.Furthermore,the immunohistochemistry results showed that PCNA expression in the endothelium of the MSC_CGRP group was lower than that of the other groups.Therefore,MSCs transfected with the CGRP gene can express the CGRP protein,and the implantation of CGRPmodified MSCs at the damaged site after carotid balloon-induced injury can reduce the neointimal area.