TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3p
Human menstrual blood-derived mesenchymal stem cells (MenSCs) and their secreted small extracellular vesicles (EVs) had been proven to relieve inflammation, tissue damage, and fibrosis in various organs. The microenvironment induced by inflammatory cytokines can promote mesenchymal stem cells (MSCs)...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2023-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2023/2988907 |
| _version_ | 1797871866975617024 |
|---|---|
| author | Huikang Xu Jiamin Fu Lijun Chen Sining Zhou Yangxin Fang Qi Zhang Xin Chen Li Yuan Yifei Li Zhenyu Xu Charlie Xiang |
| author_facet | Huikang Xu Jiamin Fu Lijun Chen Sining Zhou Yangxin Fang Qi Zhang Xin Chen Li Yuan Yifei Li Zhenyu Xu Charlie Xiang |
| author_sort | Huikang Xu |
| collection | DOAJ |
| description | Human menstrual blood-derived mesenchymal stem cells (MenSCs) and their secreted small extracellular vesicles (EVs) had been proven to relieve inflammation, tissue damage, and fibrosis in various organs. The microenvironment induced by inflammatory cytokines can promote mesenchymal stem cells (MSCs) to secrete more substances (including EVs) that could regulate inflammation. Inflammatory bowel disease (IBD) is a chronic idiopathic intestinal inflammation, the etiology and mechanism of which are unclear. At present, the existing therapeutic methods are ineffective for many patients and have obvious side effects. Hence, we explored the role of tumor necrosis factor α- (TNF-α-) pretreated MenSC-derived small EV (MenSCs-sEVTNF-α) in a mouse model of dextran sulfate sodium- (DSS-) induced colitis, expecting to find better therapeutic alterations. In this research, the small EVs of MenSCs were obtained by ultracentrifugation. MicroRNAs of small EVs derived from MenSCs before and after TNF-α treatment were sequenced, and the differential microRNAs were analyzed by bioinformatics. The small EVs secreted by TNF-α-stimulating MenSCs were more effective in colonic mice than those secreted directly by MenSCs, as evidenced by the results of histopathology analysis of colonic tissue, immunohistochemistry for tight junction proteins, and enzyme-linked immunosorbent assay (ELISA) for cytokine expression profiles in vivo. The process of MenSCs-sEVTNF-α relieving colonic inflammation was accompanied by the polarization of M2 macrophages in the colon and miR-24-3p upregulation in small EVs. In vitro, both MenSC-derived sEV (MenSCs-sEV) and MenSCs-sEVTNF-α reduced the expression of proinflammatory cytokines, and MenSCs-sEVTNF-α can increase the portion of M2 macrophages. In conclusion, after TNF-α stimulation, the expression of miR-24-3p in small EVs derived from MenSCs was upregulated. MiR-24-3p was proved to target and downregulate interferon regulatory factor 1 (IRF1) expression in the murine colon and then promoted the polarization of M2 macrophages. The polarization of M2 macrophages in colonic tissues then reduced the damage caused by hyperinflammation. |
| first_indexed | 2024-04-10T00:50:48Z |
| format | Article |
| id | doaj.art-80db556c97df453f8c403e3d97f11014 |
| institution | Directory Open Access Journal |
| issn | 1687-9678 |
| language | English |
| last_indexed | 2024-04-10T00:50:48Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj.art-80db556c97df453f8c403e3d97f110142023-03-13T11:25:38ZengHindawi LimitedStem Cells International1687-96782023-01-01202310.1155/2023/2988907TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3pHuikang Xu0Jiamin Fu1Lijun Chen2Sining Zhou3Yangxin Fang4Qi Zhang5Xin Chen6Li Yuan7Yifei Li8Zhenyu Xu9Charlie Xiang10State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesInnovative Precision Medicine (IPM) GroupState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesInnovative Precision Medicine (IPM) GroupState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesHuman menstrual blood-derived mesenchymal stem cells (MenSCs) and their secreted small extracellular vesicles (EVs) had been proven to relieve inflammation, tissue damage, and fibrosis in various organs. The microenvironment induced by inflammatory cytokines can promote mesenchymal stem cells (MSCs) to secrete more substances (including EVs) that could regulate inflammation. Inflammatory bowel disease (IBD) is a chronic idiopathic intestinal inflammation, the etiology and mechanism of which are unclear. At present, the existing therapeutic methods are ineffective for many patients and have obvious side effects. Hence, we explored the role of tumor necrosis factor α- (TNF-α-) pretreated MenSC-derived small EV (MenSCs-sEVTNF-α) in a mouse model of dextran sulfate sodium- (DSS-) induced colitis, expecting to find better therapeutic alterations. In this research, the small EVs of MenSCs were obtained by ultracentrifugation. MicroRNAs of small EVs derived from MenSCs before and after TNF-α treatment were sequenced, and the differential microRNAs were analyzed by bioinformatics. The small EVs secreted by TNF-α-stimulating MenSCs were more effective in colonic mice than those secreted directly by MenSCs, as evidenced by the results of histopathology analysis of colonic tissue, immunohistochemistry for tight junction proteins, and enzyme-linked immunosorbent assay (ELISA) for cytokine expression profiles in vivo. The process of MenSCs-sEVTNF-α relieving colonic inflammation was accompanied by the polarization of M2 macrophages in the colon and miR-24-3p upregulation in small EVs. In vitro, both MenSC-derived sEV (MenSCs-sEV) and MenSCs-sEVTNF-α reduced the expression of proinflammatory cytokines, and MenSCs-sEVTNF-α can increase the portion of M2 macrophages. In conclusion, after TNF-α stimulation, the expression of miR-24-3p in small EVs derived from MenSCs was upregulated. MiR-24-3p was proved to target and downregulate interferon regulatory factor 1 (IRF1) expression in the murine colon and then promoted the polarization of M2 macrophages. The polarization of M2 macrophages in colonic tissues then reduced the damage caused by hyperinflammation.http://dx.doi.org/10.1155/2023/2988907 |
| spellingShingle | Huikang Xu Jiamin Fu Lijun Chen Sining Zhou Yangxin Fang Qi Zhang Xin Chen Li Yuan Yifei Li Zhenyu Xu Charlie Xiang TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3p Stem Cells International |
| title | TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3p |
| title_full | TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3p |
| title_fullStr | TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3p |
| title_full_unstemmed | TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3p |
| title_short | TNF-α Enhances the Therapeutic Effects of MenSC-Derived Small Extracellular Vesicles on Inflammatory Bowel Disease through Macrophage Polarization by miR-24-3p |
| title_sort | tnf α enhances the therapeutic effects of mensc derived small extracellular vesicles on inflammatory bowel disease through macrophage polarization by mir 24 3p |
| url | http://dx.doi.org/10.1155/2023/2988907 |
| work_keys_str_mv | AT huikangxu tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT jiaminfu tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT lijunchen tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT siningzhou tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT yangxinfang tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT qizhang tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT xinchen tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT liyuan tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT yifeili tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT zhenyuxu tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p AT charliexiang tnfaenhancesthetherapeuticeffectsofmenscderivedsmallextracellularvesiclesoninflammatoryboweldiseasethroughmacrophagepolarizationbymir243p |