间充质干细胞衍生的细胞外囊泡通过促进巨噬细胞极化改变疾病结局。
Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization.
机构信息
The Children's Hospital of Zhejiang University School of Medicine and National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, Zhejiang, China.
出版信息
Stem Cell Res Ther. 2020 Sep 29;11(1):424. doi: 10.1186/s13287-020-01937-8.
Abstract
Mesenchymal stem cells (MSCs) are adult stromal cells that reside in virtually all postnatal tissues. Due to their regenerative and immunomodulatory capacities, MSCs have attracted growing attention during the past two decades. MSC-derived extracellular vesicles (MSC-EVs) are able to duplicate the effects of their parental cells by transferring functional proteins and genetic materials to recipient cells without cell-to-cell contact. MSC-EVs also target macrophages, which play an essential role in innate immunity, adaptive immunity, and homeostasis. Recent studies have demonstrated that MSC-EVs reduce M1 polarization and/or promote M2 polarization in a variety of settings. In this review, we discuss the mechanisms of macrophage polarization and roles of MSC-EV-induced macrophage polarization in the outcomes of cardiovascular, pulmonary, digestive, renal, and central nervous system diseases. In conclusion, MSC-EVs may become a viable alternative to MSCs for the treatment of diseases in which inflammation and immunity play a critical role.
摘要
间充质干细胞（MSCs）是存在于几乎所有出生后组织中的成体基质细胞。由于其再生和免疫调节能力，MSC 在过去二十年中引起了越来越多的关注。MSC 衍生的细胞外囊泡（MSC-EVs）能够通过将功能性蛋白质和遗传物质传递给靶细胞而无需细胞间接触来复制其亲本细胞的作用。MSC-EVs 还靶向巨噬细胞，巨噬细胞在先天免疫、适应性免疫和体内平衡中发挥着重要作用。最近的研究表明，MSC-EVs 在多种情况下减少 M1 极化和/或促进 M2 极化。在这篇综述中，我们讨论了巨噬细胞极化的机制以及 MSC-EV 诱导的巨噬细胞极化在心血管、肺部、消化系统、肾脏和中枢神经系统疾病结局中的作用。总之，MSC-EVs 可能成为治疗炎症和免疫发挥关键作用的疾病的 MSC 的可行替代品。
相似文献
1
Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization.间充质干细胞衍生的细胞外囊泡通过促进巨噬细胞极化改变疾病结局。
Stem Cell Res Ther. 2020 Sep 29;11(1):424. doi: 10.1186/s13287-020-01937-8.
2
Extracellular Vesicles Derived from Primed Mesenchymal Stromal Cells Loaded on Biphasic Calcium Phosphate Biomaterial Exhibit Enhanced Macrophage Polarization.包载于双相磷酸钙生物材料的预激活间充质基质细胞衍生的细胞外囊泡表现出增强的巨噬细胞极化。
Cells. 2022 Jan 29;11(3):470. doi: 10.3390/cells11030470.
3
Mesenchymal Stem Cell-Derived Extracellular Vesicles as Mediators of Anti-Inflammatory Effects: Endorsement of Macrophage Polarization.间质干细胞衍生的细胞外囊泡作为抗炎作用的介质：促进巨噬细胞极化。
Stem Cells Transl Med. 2017 Mar;6(3):1018-1028. doi: 10.1002/sctm.16-0363. Epub 2017 Jan 31.
4
Atorvastatin-pretreated mesenchymal stem cell-derived extracellular vesicles promote cardiac repair after myocardial infarction via shifting macrophage polarization by targeting microRNA-139-3p/Stat1 pathway.阿托伐他汀预处理的间充质干细胞衍生的细胞外囊泡通过靶向 microRNA-139-3p/Stat1 通路转移巨噬细胞极化促进心肌梗死后的心脏修复。
BMC Med. 2023 Mar 16;21(1):96. doi: 10.1186/s12916-023-02778-x.
5
Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis.间充质基质细胞衍生的细胞外囊泡：再生和免疫调节作用及其在脓毒症中的潜在应用。
Cell Tissue Res. 2018 Oct;374(1):1-15. doi: 10.1007/s00441-018-2871-5. Epub 2018 Jun 28.
6
Extracellular vesicles derived from human ESC-MSCs target macrophage and promote anti-inflammation process, angiogenesis, and functional recovery in ACS-induced severe skeletal muscle injury.人胚胎干细胞来源的细胞外囊泡靶向巨噬细胞，促进 ACS 诱导的严重骨骼肌损伤中的抗炎过程、血管生成和功能恢复。
Stem Cell Res Ther. 2023 Nov 14;14(1):331. doi: 10.1186/s13287-023-03530-1.
7
Mesenchymal Stromal Cells Primed by Toll-like Receptors 3 and 4 Enhanced Anti-Inflammatory Effects against LPS-Induced Macrophages via Extracellular Vesicles.TLR3/4 预刺激的间充质基质细胞通过细胞外囊泡增强对 LPS 诱导的巨噬细胞的抗炎作用。
Int J Mol Sci. 2023 Nov 13;24(22):16264. doi: 10.3390/ijms242216264.
8
Mesenchymal stem cell-derived extracellular vesicles prevent glioma by blocking M2 polarization of macrophages through a miR-744-5p/TGFB1-dependent mechanism.间质干细胞衍生的细胞外囊泡通过 miR-744-5p/TGFB1 依赖机制阻止巨噬细胞 M2 极化从而抑制神经胶质瘤。
Cell Biol Toxicol. 2022 Aug;38(4):649-665. doi: 10.1007/s10565-021-09652-7. Epub 2022 Jan 3.
9
Functional proteins of mesenchymal stem cell-derived extracellular vesicles.间充质干细胞衍生细胞外囊泡的功能蛋白。
Stem Cell Res Ther. 2019 Nov 28;10(1):359. doi: 10.1186/s13287-019-1484-6.
10
Extracellular vesicles secreted by hypoxia pre-challenged mesenchymal stem cells promote non-small cell lung cancer cell growth and mobility as well as macrophage M2 polarization via miR-21-5p delivery.缺氧预处理间充质干细胞分泌的细胞外囊泡通过 miR-21-5p 递送来促进非小细胞肺癌细胞的生长和迁移以及巨噬细胞 M2 极化。
J Exp Clin Cancer Res. 2019 Feb 8;38(1):62. doi: 10.1186/s13046-019-1027-0.
引用本文的文献
1
Exosome Therapy: A Promising Avenue for Treating Intervertebral Disc Degeneration.外泌体疗法：治疗椎间盘退变的一条有前景的途径。
Tissue Eng Regen Med. 2025 Aug 7. doi: 10.1007/s13770-025-00746-5.
2
A Paradigm Shift in SSTI Management: The Multifunctional Role of Extracellular Vesicles.皮肤和软组织感染管理的范式转变：细胞外囊泡的多功能作用
Int J Mol Sci. 2025 Jul 5;26(13):6481. doi: 10.3390/ijms26136481.
3
Extracellular Vesicles as Biomarkers in Chronic Hepatobiliary Diseases: An Overview of Their Interplay.细胞外囊泡作为慢性肝胆疾病的生物标志物：它们相互作用的概述
Int J Mol Sci. 2025 Jun 30;26(13):6333. doi: 10.3390/ijms26136333.
4
In-vitro immunomodulatory efficacy of extracellular vesicles derived from TGF-β1/IFN-γ dual licensed human bone marrow mesenchymal stromal cells.转化生长因子-β1/干扰素-γ双许可的人骨髓间充质基质细胞衍生的细胞外囊泡的体外免疫调节功效
Stem Cell Res Ther. 2025 Jul 9;16(1):357. doi: 10.1186/s13287-025-04476-2.
5
Extracellular Vesicle (EV) Targeted Cells Release Secondary Effector EVs: Indication of How To Account for Histocompatibility and Disease Specificity of EV Treatments.细胞外囊泡（EV）靶向细胞释放二级效应EV：关于如何考虑EV治疗的组织相容性和疾病特异性的说明
J Extracell Vesicles. 2025 May;14(5):e70076. doi: 10.1002/jev2.70076.
6
From bench to bedside: the research status and application opportunity of extracellular vesicles and their engineering strategies in the treatment of skin defects.从 bench 到床边：细胞外囊泡及其工程策略在皮肤缺损治疗中的研究现状与应用机遇
J Nanobiotechnology. 2025 May 25;23(1):375. doi: 10.1186/s12951-025-03461-4.
7
Mesenchymal Stem Cell-Derived Exosomes Hold Promise in the Treatment of Diabetic Foot Ulcers.间充质干细胞衍生的外泌体在糖尿病足溃疡治疗中具有前景。
Int J Nanomedicine. 2025 May 6;20:5837-5857. doi: 10.2147/IJN.S516533. eCollection 2025.
8
Therapeutic Potential of Extracellular Vesicles in Oral Inflammation.细胞外囊泡在口腔炎症中的治疗潜力
Int J Mol Sci. 2025 Mar 26;26(7):3031. doi: 10.3390/ijms26073031.
9
Extracellular vesicles and miRNA-based therapies in triple-negative breast cancer: advances and clinical perspectives.三阴性乳腺癌中的细胞外囊泡和基于微小RNA的疗法：进展与临床前景
Extracell Vesicles Circ Nucl Acids. 2025 Feb 14;6(1):54-71. doi: 10.20517/evcna.2024.85. eCollection 2025.
10
Human umbilical cord mesenchymal stem cell-derived microvesicles alleviate pulmonary fibrosis by inhibiting monocyte‒macrophage migration through ERK1/2 signaling-mediated suppression of CCL2 expression.人脐带间充质干细胞衍生的微泡通过ERK1/2信号介导的CCL2表达抑制来抑制单核细胞-巨噬细胞迁移，从而减轻肺纤维化。
Stem Cell Res Ther. 2025 Mar 24;16(1):145. doi: 10.1186/s13287-025-04266-w.
本文引用的文献
1
Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases.间充质干细胞及其外泌体在重症新型冠状病毒肺炎（COVID-19）病例中的治疗潜力
Inflamm Regen. 2020 Jun 22;40:14. doi: 10.1186/s41232-020-00121-y. eCollection 2020.
2
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Attenuate LPS-Induced ARDS by Modulating Macrophage Polarization Through Inhibiting Glycolysis in Macrophages.骨髓间充质干细胞来源的外泌体通过抑制巨噬细胞糖酵解调节巨噬细胞极化减轻脂多糖诱导的急性呼吸窘迫综合征
Shock. 2020 Dec;54(6):828-843. doi: 10.1097/SHK.0000000000001549.
3
Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage.外泌体介导的间充质基质细胞来源的 miR-21-5p 向神经元转移通过 PTEN/Akt 通路减轻蛛网膜下腔出血后早期脑损伤，改善认知功能。
Cell Death Dis. 2020 May 13;11(5):363. doi: 10.1038/s41419-020-2530-0.
4
Mesenchymal Stem Cell-Derived Extracellular Vesicles Alleviate Acute Lung Injury Via Transfer of miR-27a-3p.间充质干细胞衍生的细胞外囊泡通过转移 miR-27a-3p 缓解急性肺损伤。
Crit Care Med. 2020 Jul;48(7):e599-e610. doi: 10.1097/CCM.0000000000004315.
5
Transplantation of ACE2 Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia.血管紧张素转换酶2间充质干细胞移植改善新型冠状病毒肺炎患者的预后。
Aging Dis. 2020 Mar 9;11(2):216-228. doi: 10.14336/AD.2020.0228. eCollection 2020 Apr.
6
Mesenchymal Stem Cell-Derived Extracellular Vesicles Induce Regulatory T Cells to Ameliorate Chronic Kidney Injury.间质干细胞衍生的细胞外囊泡诱导调节性 T 细胞减轻慢性肾脏损伤。
Hypertension. 2020 May;75(5):1223-1232. doi: 10.1161/HYPERTENSIONAHA.119.14546. Epub 2020 Mar 30.
7
C-C chemokine receptor type 2-overexpressing exosomes alleviated experimental post-stroke cognitive impairment by enhancing microglia/macrophage M2 polarization.过表达C-C趋化因子受体2的外泌体通过增强小胶质细胞/巨噬细胞M2极化减轻实验性中风后认知障碍。
World J Stem Cells. 2020 Feb 26;12(2):152-167. doi: 10.4252/wjsc.v12.i2.152.
8
TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis.犬骨髓间充质干细胞来源的外泌体中的 TSG-6 是缓解 DSS 诱导的结肠炎的主要因素。
PLoS One. 2020 Feb 10;15(2):e0220756. doi: 10.1371/journal.pone.0220756. eCollection 2020.
9
Pretreatment of exosomes derived from hUCMSCs with TNF-α ameliorates acute liver failure by inhibiting the activation of NLRP3 in macrophage.预处理源自 hUCMSCs 的外泌体并用 TNF-α 处理可以通过抑制巨噬细胞中 NLRP3 的激活来改善急性肝衰竭。
Life Sci. 2020 Apr 1;246:117401. doi: 10.1016/j.lfs.2020.117401. Epub 2020 Feb 6.
10
Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization.缺氧预处理间充质干细胞来源的外泌体转移的 miR-216a-5p 通过改变小胶质细胞 M1/M2 极化来修复创伤性脊髓损伤。
J Neuroinflammation. 2020 Feb 4;17(1):47. doi: 10.1186/s12974-020-1726-7.
Zotero 插件