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揭示 hUCMSC 来源的 EVs 通过 //SLC7A11 共表达调控在椎间盘退变中的治疗潜力。

Unveiling the Therapeutic Potential of hUCMSC-Derived EVs in Intervertebral Disc Degeneration through //SLC7A11 Coexpression Regulation.

机构信息

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi, China.

Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an 710054, Shaanxi, China.

出版信息

ACS Biomater Sci Eng. 2024 Aug 12;10(8):4839-4854. doi: 10.1021/acsbiomaterials.3c01944. Epub 2024 Jul 30.

Abstract

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.

摘要

椎间盘退行性病变(IVDD)是一种常见的慢性疾病,可导致脊柱疼痛和功能障碍。本研究探讨了人脐带间充质干细胞(hUCMSCs)来源的细胞外囊泡(EVs)在调节 IVDD 中的作用。通过 RNA-seq,我们分析了来自不同小鼠组的髓核组织中 lncRNA 和 miRNA 的差异表达。我们确定了关键的调节分子 MALAT1 和 miRNA-138-5p,它们参与了 IVDD 的发生。进一步的实验表明,MALAT1 可以通过竞争性结合 miR-138-5p 来上调 SLC7A11 的表达,形成 MALAT1/miR-138-5p/SLC7A11 共表达调控网络。本研究阐明了 hUCMSC 衍生的 EVs 调节 IVDD 的分子机制,并为治疗这种疾病提供了新的治疗策略。我们的研究结果表明,hUCMSCs-EVs 抑制了髓核细胞中的铁死亡,从而改善了 IVDD。这些结果突出了 hUCMSCs-EVs 在改善 IVDD 发展中的治疗潜力,为新的治疗方法提供了重要的科学和临床意义。

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