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1.
Open Med (Wars) ; 18(1): 20220618, 2023.
Article in English | MEDLINE | ID: mdl-36660450

ABSTRACT

Inflammatory responses play a critical role in the progress of neurodegenerative disorders. MSC-Exos is considered to have an anti-inflammatory effect on the treatment strategy for brain injury. However, the therapeutic effect and possible mechanism of Exosomal miR-210 on microglia polarization-induced neuroinflammation and neurite outgrowth have not been reported. MSC-Exos were isolated by ultracentrifugation, identified by Nanosight NS300, transmission electron microscopy, and western bolt. In vitro, to explore the protective mechanism of MSC-Exos against neuroinflammation, the microglial BV2 cell was exposed to lipopolysaccharide to assess inflammatory changes. The intake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil)-MSC-Exos into microglia was observed by fluorescence microscopy. The results showed that Exosomal miR-210 treatment significantly inhibited the production of nitric oxide and pro-inflammatory cytokines. Exosomal miR-210 treatment also increased the number of M2 microglia cells and inhibited M1 microglia polarization. In addition, western blot demonstrated that Exosomal miR-210 reduced neuronal apoptosis. Thus, Exosomal miR-210 attenuated neuronal inflammation and promoted neurite outgrowth. Exosomal miR-210 from MSCs attenuated neuronal inflammation and contributed to neurogenesis possibly by inhibiting microglial M1 polarization.

2.
Article in English | MEDLINE | ID: mdl-35616673

ABSTRACT

BACKGROUND: The healing of cutaneous wounds requires better strategies, which remain a challenge. Previous reports indicated that the therapeutic function of mesenchymal stem cells is mediated by exosomes. This work demonstrated the regenerative effects of engineered BMSCsderived Exosomal miR-542-3p in skin wound mouse models. METHODS: Bone marrow mesenchymal stem cells (BMSCs) -derived exosomes (BMSCs-Exos) were isolated by ultracentrifugation and identified by Transmission Electron Microscope (TEM) and Nanoparticle Tracking Analysis (NTA). BMSCs-Exo was loaded with miRNA-542-3p by electroporation. We explored the effects of miRNA-542-3p-Exo on the proliferation and migration of Human Skin Fibroblasts (HSFs)/Human dermal microvascular endothelial cells (HMECs). In addition, The angiogenesis of HMECs was detected by Tube formation assay in vitro. The effects of miRNA-542-3p-Exo in the skin wound mouse model were detected by H&E staining, Masson staining, and immunofluorescence analysis. We assessed the effect of miRNA-542-3p-Exo on collagen deposition, new blood vessel formation, and wound remodeling in a skin wound mouse model. RESULTS: MiRNA-542-3p-Exos could be internalized by HSFs/HMECs and enhance the proliferation, migration, and angiogenesis of HSFs/HMECs in vitro and in vivo. The protein expression of collagen1/3 was significantly increased after miRNA-542-3p-Exo treatment in HSFs. In addition, the local injection of miRNA-542-3p-Exo promoted cellular proliferation, collagen deposition, neovascularization, and accelerated wound closure. CONCLUSION: This study suggested that miRNA-542-3p-Exo can stimulate HSFs/HMECs function. The treatment of miRNA-542-3p-Exo in the skin wound mouse model significantly promotes wound repair. The therapeutic potential of miRNA-542-3p-Exo may be a future therapeutic strategy for cutaneous wound healing.


Subject(s)
Mesenchymal Stem Cells , MicroRNAs , Mice , Animals , Humans , Endothelial Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Wound Healing/genetics , Collagen , Disease Models, Animal , Mesenchymal Stem Cells/metabolism
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