LinFeng Wang, Yang Wang, Jianhang Jiao, Weibo Jiang, Tong Yu, Zhonghan Wang, Mufeng Li, Minfei Wu, Pan Su
{"title":"携带 miRNAs 的间充质干细胞衍生细胞外囊泡在调节椎间盘退变中的自噬和细胞退化方面的治疗潜力","authors":"LinFeng Wang, Yang Wang, Jianhang Jiao, Weibo Jiang, Tong Yu, Zhonghan Wang, Mufeng Li, Minfei Wu, Pan Su","doi":"10.1097/BRS.0000000000005167","DOIUrl":null,"url":null,"abstract":"<p><strong>Study design: </strong>This research utilized bioinformatics and in vitro modeling to assess the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) containing specific microRNAs (miRNAs) on the autophagy and degeneration of nucleus pulposus cells in intervertebral disc degeneration (IDD).</p><p><strong>Objective: </strong>To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathologic changes in IDD.</p><p><strong>Background: </strong>IDD is characterized by changes in gene expression that contribute to cell degeneration and reduced disc integrity. MSC-EVs are known for their role in cellular communication and potentially reversing these degenerative processes.</p><p><strong>Materials and methods: </strong>Key differentially expressed miRNAs and mRNAs in MSC-EVs were identified using bioinformatics analysis. Three miRNAs (miR-486-5p, miR-3648, and miR-1827) typically downregulated in IDD were selected for further study. The bone marrow-derived MSC-EVs used in this study were cultured in a two-dimensional environment. These MSC-EVs were isolated with the purpose of delivering the selected miRNAs to IDD nucleus pulposus cells in vitro, targeting specifically the upregulated genes ( SMAD2 , ESR1 , MAVS , and MMP14 ) associated with autophagy and degeneration.</p><p><strong>Results: </strong>MSC-EV treatment led to significant downregulation of target genes, enhanced cellular proliferation, and decreased apoptosis and autophagy. Overexpression of these target genes produced the opposite effects, confirming the miRNAs' regulatory roles.</p><p><strong>Conclusions: </strong>MSC-EVs carrying specific miRNAs can effectively modulate gene expression, reduce degenerative processes, and promote cellular proliferation in IDD, indicating a promising therapeutic strategy for treating IDD and potentially other degenerative diseases. Further investigations are warranted to explore MSC-EV applications in regenerative medicine.</p>","PeriodicalId":22193,"journal":{"name":"Spine","volume":" ","pages":"E7-E19"},"PeriodicalIF":2.6000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNAs for Modulating Autophagy and Cellular Degeneration in Intervertebral Disc Degeneration.\",\"authors\":\"LinFeng Wang, Yang Wang, Jianhang Jiao, Weibo Jiang, Tong Yu, Zhonghan Wang, Mufeng Li, Minfei Wu, Pan Su\",\"doi\":\"10.1097/BRS.0000000000005167\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Study design: </strong>This research utilized bioinformatics and in vitro modeling to assess the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) containing specific microRNAs (miRNAs) on the autophagy and degeneration of nucleus pulposus cells in intervertebral disc degeneration (IDD).</p><p><strong>Objective: </strong>To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathologic changes in IDD.</p><p><strong>Background: </strong>IDD is characterized by changes in gene expression that contribute to cell degeneration and reduced disc integrity. MSC-EVs are known for their role in cellular communication and potentially reversing these degenerative processes.</p><p><strong>Materials and methods: </strong>Key differentially expressed miRNAs and mRNAs in MSC-EVs were identified using bioinformatics analysis. Three miRNAs (miR-486-5p, miR-3648, and miR-1827) typically downregulated in IDD were selected for further study. The bone marrow-derived MSC-EVs used in this study were cultured in a two-dimensional environment. These MSC-EVs were isolated with the purpose of delivering the selected miRNAs to IDD nucleus pulposus cells in vitro, targeting specifically the upregulated genes ( SMAD2 , ESR1 , MAVS , and MMP14 ) associated with autophagy and degeneration.</p><p><strong>Results: </strong>MSC-EV treatment led to significant downregulation of target genes, enhanced cellular proliferation, and decreased apoptosis and autophagy. Overexpression of these target genes produced the opposite effects, confirming the miRNAs' regulatory roles.</p><p><strong>Conclusions: </strong>MSC-EVs carrying specific miRNAs can effectively modulate gene expression, reduce degenerative processes, and promote cellular proliferation in IDD, indicating a promising therapeutic strategy for treating IDD and potentially other degenerative diseases. Further investigations are warranted to explore MSC-EV applications in regenerative medicine.</p>\",\"PeriodicalId\":22193,\"journal\":{\"name\":\"Spine\",\"volume\":\" \",\"pages\":\"E7-E19\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Spine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/BRS.0000000000005167\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Spine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/BRS.0000000000005167","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/2 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNAs for Modulating Autophagy and Cellular Degeneration in Intervertebral Disc Degeneration.
Study design: This research utilized bioinformatics and in vitro modeling to assess the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) containing specific microRNAs (miRNAs) on the autophagy and degeneration of nucleus pulposus cells in intervertebral disc degeneration (IDD).
Objective: To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathologic changes in IDD.
Background: IDD is characterized by changes in gene expression that contribute to cell degeneration and reduced disc integrity. MSC-EVs are known for their role in cellular communication and potentially reversing these degenerative processes.
Materials and methods: Key differentially expressed miRNAs and mRNAs in MSC-EVs were identified using bioinformatics analysis. Three miRNAs (miR-486-5p, miR-3648, and miR-1827) typically downregulated in IDD were selected for further study. The bone marrow-derived MSC-EVs used in this study were cultured in a two-dimensional environment. These MSC-EVs were isolated with the purpose of delivering the selected miRNAs to IDD nucleus pulposus cells in vitro, targeting specifically the upregulated genes ( SMAD2 , ESR1 , MAVS , and MMP14 ) associated with autophagy and degeneration.
Results: MSC-EV treatment led to significant downregulation of target genes, enhanced cellular proliferation, and decreased apoptosis and autophagy. Overexpression of these target genes produced the opposite effects, confirming the miRNAs' regulatory roles.
Conclusions: MSC-EVs carrying specific miRNAs can effectively modulate gene expression, reduce degenerative processes, and promote cellular proliferation in IDD, indicating a promising therapeutic strategy for treating IDD and potentially other degenerative diseases. Further investigations are warranted to explore MSC-EV applications in regenerative medicine.
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Recognized internationally as the leading journal in its field, Spine is an international, peer-reviewed, bi-weekly periodical that considers for publication original articles in the field of Spine. It is the leading subspecialty journal for the treatment of spinal disorders. Only original papers are considered for publication with the understanding that they are contributed solely to Spine. The Journal does not publish articles reporting material that has been reported at length elsewhere.
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