Inflammation-Stimulated MSC-Derived Small Extracellular Vesicle miR-27b-3p Regulates Macrophages by Targeting CSF-1 to Promote Temporomandibular Joint Condylar Regeneration
Inflammation-Stimulated MSC-Derived Small Extracellular Vesicle miR-27b-3p Regulates Macrophages by Targeting CSF-1 to Promote Temporomandibular Joint Condylar Regeneration
复制标题
炎症刺激的 MSC 衍生的小细胞外囊泡 miR-27b-3p 通过靶向 CSF-1 来调节巨噬细胞，促进颞下颌关节髁再生。
DOI：
10.1002/smll.202107354
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发表时间：
2022-03-11
期刊：
影响因子：
13.3
通讯作者：
Wang, Shufang
中科院分区：
文献类型：
--
作者：
Liu, Yufei;Zhang, Zhiling;Wang, Shufang
间充质干细胞（mesenchymal stem cells，MSCs）分泌的细胞外小泡（Small extracellular vesicles，sEVs）是近年来研究的热点。sEV含量随分泌细胞状态而变化。当MSC暴露于炎症环境时，它们释放更多的功能性生长因子，外泌体和趋化因子。在本文中，MSC被刺激以改变sEV货物和功能以调节炎症微环境并促进组织再生。sEV miRNAs的测序显示，某些有益于细胞功能的RNA被上调。在这项研究中，体外细胞功能实验表明，炎症刺激的脂肪来源的MSC（ADSC）衍生的sEV（IAE）和正常ADSC衍生的sEV（AE）都促进细胞增殖; IAE还显著改善细胞迁移。关于巨噬细胞极化调节，IAE显著促进M2巨噬细胞分化。RNA测序分析表明，miR-27 b-3 p在IAE中的高表达水平可能通过靶向巨噬细胞集落刺激因子-1（CSF-1）来调节巨噬细胞。在体内，兔颞下颌关节（TMJ）髁突骨软骨缺损模型表明，AE和IAE都促进TMJ再生，IAE具有最显著的治疗效果。因此，作者证实，将MSC暴露于炎症环境可以切实增强sEV功能，并且修饰的sEV实现更好的治疗效果。
Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have been extensively studied in recent years. sEV contents change with the secreting cell state. When MSCs are exposed to an inflammatory environment, they release more functional growth factors, exosomes, and chemokines. Herein, MSCs are stimulated to alter sEV cargos and functions to regulate the inflammatory microenvironment and promote tissue regeneration. Sequencing of sEV miRNAs shows that certain RNAs conducive to cell function are upregulated. In this study, in vitro cell function experiments show that both inflammation-stimulated adipose-derived MSC (ADSC)-derived sEV (IAE) and normal ADSC-derived sEV (AE) promote cell proliferation; IAE also significantly improves cell migration. Regarding macrophage polarization regulation, IAE significantly promotes M2 macrophage differentiation. RNA-sequencing analysis indicates that high miR-27b-3p expression levels in IAE may regulate macrophages by targeting macrophage colony-stimulating factor-1 (CSF-1). In vivo, a rabbit temporomandibular joint (TMJ) condylar osteochondral defect model shows that both AE and IAE promote TMJ regeneration, with IAE having the most significant therapeutic effect. Therefore, the authors confirm that exposing MSCs to an inflammatory environment can feasibly enhance sEV functions and that modified sEVs achieve better therapeutic effects.