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来自带介质干细胞的外体细胞通过修复线粒体功能障碍来改善椎间盘退化

Shu Jia^1,2, Tao Yang³, Sheng Gao³

¹Clinical Research Team of Spine & Spinal Cord Diseases, Medical Research Center, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong Province, 272000, China.

Journal of orthopaedic translation

|June 6, 2024

概括

带介质干细胞外体 (UCMSC-exos) 通过减少氧化应激和改善线粒体功能,有效地治疗椎间盘退化 (IVDD). 这些外基因组显示为IVDD的纳米疗法有前途.

科学领域:

介质细胞干细胞生物学介质细胞干细胞生物学
细胞外囊泡细胞外囊泡
线粒体生物学线粒体生物学

背景情况:

反应性氧物种 (ROS) 驱动椎间盘退化 (IVDD) 病原体,主要是通过线粒体功能障碍.
降低ROS水平是延缓IVDD进展的潜在治疗策略.
带介质干细胞外生体 (UCMSC-exos) 正在研究它们在IVDD中减轻ROS产生的潜力.

研究的目的:

评估UCMSC外体在治疗IVDD中的治疗疗效.
研究UCMSC外体抑制ROS产生和线粒体功能障碍的机制.
评估UCMSC外体对细胞外基质合成和细胞核细胞 (NPC) 中细胞活力的影响.

主要方法:

人类UCMSC外体的隔离和鉴定.
在实验室中使用H2O2刺激的NPC治疗UCMSC外体的研究.
蛋白质组分析 (4D-LFQ),免疫光学,流细胞测量,西部涂抹和高通量测序以评估细胞和分子变化.
在刺穿诱导的IVDD小鼠模型中的体内评估,使用MRI和体化学染色.

主要成果:

UCMSC外基因组增强了NPC活力,并恢复了细胞外基质 (ECM) 蛋白表达 (COL2A1).
UCMSC-外基因组降低了细胞内和线粒体ROS水平,增加了线粒体膜潜力 (MMP) 和调高了线粒体转录因子A (TFAM).
UCMSC外基因组降低了TFAM的负调节者miR-194-5p,并在IVDD大鼠模型中改善了他的病理结构.

结论:

UCMSC外体促进ECM合成,并减轻线粒体氧化应激和IVDD中的功能障碍.
UCMSC外体体在体外和体内都显示出显著的治疗效果,为IVDD治疗提供了有前途的纳米疗法.

关键词:

外基因组是外基因组的组成部分.椎间盘退化椎间盘退化线粒体中的线粒体.带介质干细胞是带介质干细胞.

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