Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosis
Abstract Background Multiple sclerosis (MS) is a progressive autoimmune disease characterized by massive inflammatory infiltration, demyelination, and subsequent axonal injury and neuronal damage in the central nervous system (CNS). The etiology of MS remains unclear and there is not yet a definitiv...
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2025-06-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04401-7 |
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| author | Xin Xiu Sijia Chen Yumei Liu Bo Sun Hulun Li Sifan Zhang Xixi Yang Yu Wei Xichen Peng Yan Wang Yanping Wang Junfeng Wu Yao Zhang Lili Mu Qingfei Kong Xijun Liu |
| author_facet | Xin Xiu Sijia Chen Yumei Liu Bo Sun Hulun Li Sifan Zhang Xixi Yang Yu Wei Xichen Peng Yan Wang Yanping Wang Junfeng Wu Yao Zhang Lili Mu Qingfei Kong Xijun Liu |
| author_sort | Xin Xiu |
| collection | DOAJ |
| description | Abstract Background Multiple sclerosis (MS) is a progressive autoimmune disease characterized by massive inflammatory infiltration, demyelination, and subsequent axonal injury and neuronal damage in the central nervous system (CNS). The etiology of MS remains unclear and there is not yet a definitive therapeutic schedule for the disease. Bone marrow mesenchymal stem cells (BMSCs), exhibiting neuroimmune-modulatory functions to alleviate various autoimmune diseases, show great potential in the treatment of MS. However, the instability of BMSCs-mediated immunosuppression in vivo has limited their application. MiR181-a, a positive regulator of immune balance, which has a preference for T cells and B cells differentiation, but degrade rapidly upon entering systemic circulation due to their unstable molecular structure. Methods We propose a synergistic therapy approach that combines the penetrative targeting capability of BMSCs with the immuno-modulatory effects of miR181-a by overexpressing miR181-a to BMSCs through lentivirus packaging system. With this strategy, on the basis of the establishment of the experimental autoimmune encephalomyelitis (EAE) model, miR181-a overexpressing BMSCs (miR181a-BMSCs) would have a stronger immuno-modulatory treatment benefit, in terms of attenuating MS development. Results Indicate that this method prolongs the modulatory effects of BMSCs and resulted in significantly enhancements of the proliferation of regulatory B cells (Bregs), regulatory T cells (Tregs) and the inhibition of Th17 cells compared to the traditional BMSCs group. Moreover, 10-fold miRNA’s concentration in the exosome of miR181a-BMSCs, leading to an increased duration of miRNAs to exert their biological effects. By immunotherapy and synergistic treatment, the effectiveness of the treatment is significantly enhanced, showing consistent results in different groups of the animal model. Conclusions This strategy takes advantage of BMSCs and miRNA and thus presents an effective synergistic strategy for the treatment of autoimmune diseases. |
| format | Article |
| id | doaj-art-4c770fb857b04c89a3b005c0230d76bb |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-4c770fb857b04c89a3b005c0230d76bb2025-08-20T03:45:11ZengBMCStem Cell Research & Therapy1757-65122025-06-0116111510.1186/s13287-025-04401-7Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosisXin Xiu0Sijia Chen1Yumei Liu2Bo Sun3Hulun Li4Sifan Zhang5Xixi Yang6Yu Wei7Xichen Peng8Yan Wang9Yanping Wang10Junfeng Wu11Yao Zhang12Lili Mu13Qingfei Kong14Xijun Liu15Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Harbin Medical UniversityAbstract Background Multiple sclerosis (MS) is a progressive autoimmune disease characterized by massive inflammatory infiltration, demyelination, and subsequent axonal injury and neuronal damage in the central nervous system (CNS). The etiology of MS remains unclear and there is not yet a definitive therapeutic schedule for the disease. Bone marrow mesenchymal stem cells (BMSCs), exhibiting neuroimmune-modulatory functions to alleviate various autoimmune diseases, show great potential in the treatment of MS. However, the instability of BMSCs-mediated immunosuppression in vivo has limited their application. MiR181-a, a positive regulator of immune balance, which has a preference for T cells and B cells differentiation, but degrade rapidly upon entering systemic circulation due to their unstable molecular structure. Methods We propose a synergistic therapy approach that combines the penetrative targeting capability of BMSCs with the immuno-modulatory effects of miR181-a by overexpressing miR181-a to BMSCs through lentivirus packaging system. With this strategy, on the basis of the establishment of the experimental autoimmune encephalomyelitis (EAE) model, miR181-a overexpressing BMSCs (miR181a-BMSCs) would have a stronger immuno-modulatory treatment benefit, in terms of attenuating MS development. Results Indicate that this method prolongs the modulatory effects of BMSCs and resulted in significantly enhancements of the proliferation of regulatory B cells (Bregs), regulatory T cells (Tregs) and the inhibition of Th17 cells compared to the traditional BMSCs group. Moreover, 10-fold miRNA’s concentration in the exosome of miR181a-BMSCs, leading to an increased duration of miRNAs to exert their biological effects. By immunotherapy and synergistic treatment, the effectiveness of the treatment is significantly enhanced, showing consistent results in different groups of the animal model. Conclusions This strategy takes advantage of BMSCs and miRNA and thus presents an effective synergistic strategy for the treatment of autoimmune diseases.https://doi.org/10.1186/s13287-025-04401-7Multiple sclerosisBone marrow mesenchymal stem cellsMiR181-aB cellsT cells |
| spellingShingle | Xin Xiu Sijia Chen Yumei Liu Bo Sun Hulun Li Sifan Zhang Xixi Yang Yu Wei Xichen Peng Yan Wang Yanping Wang Junfeng Wu Yao Zhang Lili Mu Qingfei Kong Xijun Liu Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosis Stem Cell Research & Therapy Multiple sclerosis Bone marrow mesenchymal stem cells MiR181-a B cells T cells |
| title | Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosis |
| title_full | Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosis |
| title_fullStr | Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosis |
| title_full_unstemmed | Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosis |
| title_short | Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosis |
| title_sort | synergistic potential of bone marrow mesenchymal stem cells and mir181 a combinational therapy against multiple sclerosis |
| topic | Multiple sclerosis Bone marrow mesenchymal stem cells MiR181-a B cells T cells |
| url | https://doi.org/10.1186/s13287-025-04401-7 |
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