Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNAs for Modulating Autophagy and Cellular Degeneration in Intervertebral Disc Degeneration.

IF 2.6 2区 医学 Q2 CLINICAL NEUROLOGY Spine Pub Date : 2025-01-01 Epub Date: 2024-10-02 DOI:10.1097/BRS.0000000000005167
LinFeng Wang, Yang Wang, Jianhang Jiao, Weibo Jiang, Tong Yu, Zhonghan Wang, Mufeng Li, Minfei Wu, Pan Su
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Abstract

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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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
研究设计:本研究利用生物信息学和体外建模评估间充质干细胞衍生的细胞外囊泡(MSC-EVs)含有特定的microRNAs(miRNAs)对椎间盘退行性变(IDD)中髓核(NP)细胞自噬和退化的影响:目的:确定含有 miRNAs 的间充质干细胞-EVs 在调节 IDD 病理变化方面的治疗潜力:IDD的特点是基因表达发生变化,导致细胞变性和椎间盘完整性降低。间充质干细胞-EVs因其在细胞交流中的作用而闻名,并有可能逆转这些退化过程:方法:通过生物信息学分析,确定了间充质干细胞-EVs 中关键的差异表达 miRNA 和 mRNA。方法:通过生物信息学分析确定了间充质干细胞-EVs中关键的差异表达 miRNA 和 mRNA,并选择了在 IDD 中典型下调的三个 miRNA(miR-486-5p、miR-3648 和 miR-1827)进行进一步研究。本研究中使用的骨髓间充质干细胞-EV是在二维环境中培养的。分离这些间充质干细胞-EV的目的是在体外向IDD NP细胞传递所选的miRNA,特别是针对与自噬和变性相关的上调基因(SMAD2、ESR1、MAVS、MMP14):结果:间充质干细胞-EV处理导致靶基因显著下调、细胞增殖增强、细胞凋亡和自噬减少。这些靶基因的过表达产生了相反的效果,证实了 miRNAs 的调控作用:结论:携带特定 miRNAs 的间充质干细胞-EVs 能有效调节 IDD 的基因表达、减少退行性病变过程并促进细胞增殖,为治疗 IDD 及其他潜在的退行性疾病提供了一种前景广阔的治疗策略。探索间充质干细胞-EV在再生医学中的应用还有待进一步研究。
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来源期刊
Spine
Spine 医学-临床神经学
CiteScore
5.90
自引率
6.70%
发文量
361
审稿时长
6.0 months
期刊介绍: Lippincott Williams & Wilkins is a leading international publisher of professional health information for physicians, nurses, specialized clinicians and students. For a complete listing of titles currently published by Lippincott Williams & Wilkins and detailed information about print, online, and other offerings, please visit the LWW Online Store. 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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