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人类胆管MSCs复制性衰老对其EV-miRNA配置文件的影响

Hedviga Košuthová¹, Lívia K Fecskeová², Jana Matejová¹

¹Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 04011, Kosice, Slovakia.

Stem cell reviews and reports

|September 21, 2024

概括

这项研究揭示了外细胞囊泡 (EV) 的微RNA (miRNA) 概况如何随着细胞衰老而发生变化. 确定了与衰老相关的关键miRNA,为扩展治疗应用提供了潜在的点.

科学领域:

干细胞生物学干细胞生物学
细胞外囊泡研究研究
介质细胞流体细胞生物学

背景情况:

胆管介质干细胞 (CHO-MSCs) 是介质干细胞 (MSCs) 的可获得和道德健全的来源.
来自CHO-MSCs的细胞外囊泡 (EVs) 具有治疗前景,但它们的miRNA配置文件需要彻底表征,特别是关于细胞衰老.
有限的研究已经研究了传递对CHO-MSC衍生的EVs的miRNA含量的影响.

研究的目的:

为了研究在序列传递过程中人类CHO-MSCs的EV-miRNA概况的变化,诱导细胞衰老.
在EV中识别特定的差异表达的miRNAs从早期与晚期通道的CHO-MSCs.
探索这些改变的miRNA与细胞衰老途径的关联.

主要方法:

通过序列传递诱导CHO-MSC衰老,通过形态变化,端粒缩短和基因表达得到证实.
从早期和晚期通道CHO-MSCs中对EVs的隔离和表征.
下一代测序以分析EV-miRNA和使用KEGG通路分析进行差异表达分析.

主要成果:

在CHO-MSC中成功诱导细胞衰老,而没有改变关键的MSC表面标记物 (CD73,CD90,CD105).
在早期和晚期通道之间,电动汽车的数量和大小保持一致.
确定了37种明显差异表达的EV-miRNA,其中23种与细胞衰老途径有关. 值得注意的是,miR-145-5p,miR-335-5p和miR-199b-3p的调节下降,而miR-1307-3p,miR-3615和miR320b在晚期通过时被调节上升.

结论:

细胞衰老显著改变了CHO-MSCs的EV-miRNA特征.
晚期EV中的特定下调 (例如miR-145-5p) 和上调 (例如miR-1307-3p) 的miRNA与衰老有关.
针对这些已识别的miRNAs可能是维持或恢复CHO-MSC衍生的EVs治疗潜力的策略.

关键词:

胆管介质细胞胆管介质细胞 stromal 细胞细胞外囊泡中的细胞外囊泡.复制性衰老是一种复制性衰老.这是一个小RNARNA.

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