人类骨髓中介质 stromal 细胞的与年龄相关的变化:形态,基因表达特征,免疫调节活性和miRNA表达
Fulvio Massaro1,2, Florent Corrillon3, Basile Stamatopoulos3
1Department of Hematology, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Frontiers in immunology
|December 22, 2023
概括
衰老的介酶体 stromal 细胞 (MSCs) 呈现出改变的形态和功能,影响免疫反应,并可能导致癌症等与年龄相关的疾病. 来自老年捐赠者的MSCs中的这些变化凸显了老化骨髓微环境的作用.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 老年学是一门学科.
背景情况:
- 介酶体 stromal 细胞 (MSCs) 在骨髓 (BM) 微环境中对组织再生和免疫调节至关重要.
- 与MSCs与年龄相关的变化有助于炎症并增加对与年龄相关的疾病 (包括癌症) 的易感性.
- 人类MSC与年龄相关的变化存在有限的研究,大多数数据来自小鼠模型或复制性衰老研究.
研究的目的:
- 从年轻的 (yBM-MSC) 和老的 (oBM-MSC) 健康捐赠者中识别人类骨髓衍生MSC的形态,分子和功能差异.
- 调查衰老对MSC免疫调节能力的影响,特别是关于巨细胞两极分化.
主要方法:
- 人类BM-MSC的特征是细胞表面标记 (ISCT标准).
- 这些MSC暴露于炎症性细胞因子 (IL-1β,IFN-α,IFN-ɣ,TNF-α).
- 在共同培养系统中,使用基因表达 (实时PCR) 和细胞因子分析 (ELISA) 评估了巨M1两极化.
主要成果:
- 旧的BM-MSCs (oBM-MSCs) 呈现出改变的大小,形态和颗粒度,增加了β-Gal,ROS,IL-6和IL-8.
- oBM-MSCs显示出殖民地形成能力和细胞周期进展受损.
- oBM-MSCs表现出免疫调节活性降低,包括对巨细胞M1极化抑制的降低,以及改变的miRNA表达 (例如,在共同培养后增加miR-193b-3p).
结论:
- 在yBM-MSCs和oBM-MSCs之间的形态,基因表达,miRNA配置文件和免疫调节功能方面存在显著差异.
- 衰老对骨髓微环境产生深远的影响,影响MSC衰老和免疫失调.
- 这些MSC变化与免疫介导疾病和癌症病原发生有关.
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