Bone marrow mesenchymal stem cell-derived exosomal microRNA-125a promotes M2 macrophage polarization in spinal cord injury by downregulating IRF5.

Spinal cord injury (SCI) may cause loss of locomotor function, and macrophage is a major cell type in response to SCI with M1- and M2-phenotypes. The protective role of bone marrow mesenchymal stem cells (BMMSC)-derived exosomes (B-Exo) in SCI has been underscored, while their regulation on M2 macrophage polarization and the mechanism remain to be clarified. A rat model of SCI was developed and treated with extracted B-Exo. Recovery of motor function was assessed by Basso-Beattie-Bresnahan (BBB) score. The apoptosis and degeneration of neurons, and macrophage polarization were evaluated. Subsequently, genes differentially expressed in the rat spinal cord after B-Exo treatment were analyzed. Later, the relationships between B-Exo and interferon regulatory factor 5 (IRF5) or macrophage polarization were clarified. Later, the upstream microRNAs (miRNAs) of IRF5 were validated by bioinformatics prediction and dual-luciferase experiments. Finally, the role of miR-125a in the neuroprotection of SCI was verified by rescue experiments. B-Exo promoted the recovery of locomotor function and M2-phenotype polarization, whereas inhibited neuronal apoptosis and degeneration and the inflammatory response caused by SCI in rats. In addition, IRF5 expression was reduced after B-Exo treatment. IRF5 promoted macrophage polarization towards M1-phenotype and secretion of inflammatory factors. There is a binding relationship between miR-125a and IRF5. Knockdown of miR-125a in B-Exo increased IRF5 expression in spinal cord tissues of SCI rats and attenuated the neuroprotective effect of B-Exo against SCI. Exosomal miR-125a derived from BMMSC exerts neuroprotective effects by targeting and negatively regulating IRF5 expression in SCI rats.

Chang Q ，Hao Y ，Wang Y ，Zhou Y ，Zhuo H ，Zhao G ... -  《-》

Bone marrow mesenchymal stem cell-derived exosomal microRNA-124-3p attenuates neurological damage in spinal cord ischemia-reperfusion injury by downregulating Ern1 and promoting M2 macrophage polarization.

Li R ，Zhao K ，Ruan Q ，Meng C ，Yin F ... -  《-》

Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway.

Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.

Gong ZT ，Xiong YY ，Ning Y ，Tang RJ ，Xu JY ，Jiang WY ，Li XS ，Zhang LL ，Chen C ，Pan Q ，Hu MJ ，Xu J ，Yang YJ ... -  《International Journal of Nanomedicine》

Exosomes with high level of miR-181c from bone marrow-derived mesenchymal stem cells inhibit inflammation and apoptosis to alleviate spinal cord injury.

Zhang M ，Wang L ，Huang S ，He X ... -  《-》

Alleviation of Spinal Cord Injury by MicroRNA 137-Overexpressing Bone Marrow Mesenchymal Stem Cell-Derived Exosomes.

Shao Y ，Wang Q ，Liu L ，Wang J ，Wu M ... -  《-》