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来自脂肪的MSC细胞外囊泡通过通过miR-21-5p向PELI1的重编程巨细胞来改善败血症

Guannan Zhou¹, Jieqiong Song², Lizhen Xuan²

¹Department of Intensive Care Unit, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Biomolecules & biomedicine

|October 27, 2025

概括

脂肪酶衍生的中酶体 stromal 细胞外细胞囊泡 (ADMSC-EVs) 显示出治疗败血症的前景. 这些EVs重编程巨细胞,减少炎症,并通过提供miR-21-5p.p.在败血症模型中改善生存率.

科学领域:

免疫学免疫学免疫学
纳米医学是一种纳米医学.
再生医学是一种再生医学.

背景情况:

败血症是一种严重的疾病,通常在重症监护室 (ICU) 接受治疗.
介酶体 stromal 细胞 (MSCs) 和它们的细胞外囊泡 (EVs) 被探索为纳米疗法.
脂肪酸衍生的MSC EVs (ADMSC-EVs) 正在研究用于败血症治疗.

研究的目的:

为了评估ADMSC-EVs在脂多糖 (LPS) 诱导的败血症模型中的疗效.
阐明ADMSC-EVs对巨细胞极化和炎症的治疗作用背后的机制.
评估ADMSC-EVs作为治疗败血症的无细胞疗法的潜力.

主要方法:

隔离了ADMSC-EV并给了LPS挑战的小鼠.
在肺组织中通过流动细胞计和免疫光学分析了巨细胞的表型.
追踪了EV生物分布,并检查了分子通路 (miR-21-5p针对PELI1).

主要成果:

发现ADMSC-EVs进入巨细胞,促进M2极化和抑制炎症.
用ADMSC-EVs治疗的败血性小鼠表现出改善的生存率.
生物分布研究表明,EVs在肺,肝脏和脏中显著积累.
确定了EV货物miR-21-5p作为一个关键的调解者,针对PELI1驱动M2极化并增加IL-10水平.

结论:

ADMSC-EVs在LPS诱导的败血症中显示出显著的治疗潜力.
该机制涉及miR-21-5p传递到PELI1,导致M2巨细胞两极分化和减少炎症.
ADMSC-EVs代表了治疗败血症的有希望的无细胞免疫调节策略.

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Mesenchymal Stem Cells

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...