BACKGROUND:Macrophages are an important part of innate immunity.When the internal environment of the body changes,macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function.Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body,which have the functions of intercellular signaling and immune regulation.Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases.OBJECTIVE:To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages,as well as the related research progress of engineered extracellular vesicles in this field.METHODS:The first author searched the relevant literature published in PubMed,CNKI and other databases until June 2024.Chinese search terms were"mesenchymal stem cells,extracellular vesicles,exosomes,apoptotic bodies,apoptotic vesicles,macrophage polarization,M1 polarization,M2 polarization,autoimmune diseases,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,type 1 diabetes mellitus,inflammatory bowel disease,autoimmune dacryadenitis,engineered extracellular vesicles,engineering exosomes,drug delivery."English search terms were"macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery."The title and abstract of each paper were read and initially screened.Finally,70 articles were selected for induction and analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional proteins.(2)Mesenchymal stem cells can regulate macrophage M2 polarization through inflammasome.(3)Mesenchymal stem cells can be combined with commonly used drugs to enhance drug efficacy.(4)Mesenchymal stem cells can regulate the release of mesenchymal stem cells-extracellular vesicles after inflammatory stimulation and affect the polarization of macrophages.(5)Mesenchymal stem cells-extracellular vesicles can regulate autoimmune diseases by targeting macrophage polarization through PTEN,NOTCH,nuclear factor κB,Toll-like receptors,PI3K/AKT and other pathways.(6)Engineered extracellular vesicles can achieve non-invasive targeted drug delivery,prolong the half-life of drugs,promote the oral administration of exosomes,reduce allograft reaction,improve the bioavailability of Chinese herbs and overcome the blood-brain barrier,opening up a new path for drug delivery.

BACKGROUND:Macrophages are an important part of innate immunity.When the internal environment of the body changes,macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function.Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body,which have the functions of intercellular signaling and immune regulation.Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases.OBJECTIVE:To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages,as well as the related research progress of engineered extracellular vesicles in this field.METHODS:The first author searched the relevant literature published in PubMed,CNKI and other databases until June 2024.Chinese search terms were"mesenchymal stem cells,extracellular vesicles,exosomes,apoptotic bodies,apoptotic vesicles,macrophage polarization,M1 polarization,M2 polarization,autoimmune diseases,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,type 1 diabetes mellitus,inflammatory bowel disease,autoimmune dacryadenitis,engineered extracellular vesicles,engineering exosomes,drug delivery."English search terms were"macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery."The title and abstract of each paper were read and initially screened.Finally,70 articles were selected for induction and analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional proteins.(2)Mesenchymal stem cells can regulate macrophage M2 polarization through inflammasome.(3)Mesenchymal stem cells can be combined with commonly used drugs to enhance drug efficacy.(4)Mesenchymal stem cells can regulate the release of mesenchymal stem cells-extracellular vesicles after inflammatory stimulation and affect the polarization of macrophages.(5)Mesenchymal stem cells-extracellular vesicles can regulate autoimmune diseases by targeting macrophage polarization through PTEN,NOTCH,nuclear factor κB,Toll-like receptors,PI3K/AKT and other pathways.(6)Engineered extracellular vesicles can achieve non-invasive targeted drug delivery,prolong the half-life of drugs,promote the oral administration of exosomes,reduce allograft reaction,improve the bioavailability of Chinese herbs and overcome the blood-brain barrier,opening up a new path for drug delivery.