Wang LinFeng, Wang Yang, Jiao Jianhang, Jiang Weibo, Yu Tong, Wang Zhonghan, Li Mufeng, Wu Minfei, Su Pan
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, China.
Spine (Phila Pa 1976). 2025 Jan 1;50(1):E7-E19. doi: 10.1097/BRS.0000000000005167. Epub 2024 Oct 2.
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).
To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathologic changes in IDD.
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.
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.
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.
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.
本研究利用生物信息学和体外模型，评估含有特定微小RNA（miRNA）的间充质干细胞衍生细胞外囊泡（MSC-EV）对椎间盘退变（IDD）中髓核细胞自噬和退变的影响。
确定装载miRNA的MSC-EV在调节IDD病理变化方面的治疗潜力。
IDD的特征是基因表达变化，这会导致细胞退变和椎间盘完整性降低。MSC-EV以其在细胞通讯中的作用以及潜在地逆转这些退变过程而闻名。
使用生物信息学分析鉴定MSC-EV中关键的差异表达miRNA和mRNA。选择在IDD中通常下调的三种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源性MSC-EV在二维环境中培养。分离这些MSC-EV的目的是在体外将选定的miRNA递送至IDD髓核细胞，特异性靶向与自噬和退变相关的上调基因（SMAD2、ESR1、MAVS和MMP14）。
MSC-EV处理导致靶基因显著下调，细胞增殖增强，凋亡和自噬减少。这些靶基因的过表达产生相反的效果，证实了miRNA的调节作用。
携带特定miRNA的MSC-EV可有效调节基因表达，减少退变过程，促进IDD中的细胞增殖，表明这是一种治疗IDD及潜在其他退行性疾病的有前景的治疗策略。有必要进行进一步研究以探索MSC-EV在再生医学中的应用。
