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细胞外囊泡治疗实体器官缺血再灌注损伤。

Extracellular vesicles for treatment of solid organ ischemia-reperfusion injury.

机构信息

Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida, USA.

Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, Florida, USA.

出版信息

Am J Transplant. 2020 Dec;20(12):3294-3307. doi: 10.1111/ajt.16164. Epub 2020 Jul 28.

Abstract

As the incidence of ischemia-reperfusion (I-R) injury has substantially increased, there is a pressing need to develop effective strategies to treat this global health issue. I-R injury can affect all organs and is associated with high morbidity and mortality rates. Pathological settings such as myocardial infarction, stroke, hemorrhagic shock, and solid organ transplant are particularly prone to cause I-R injury. Ischemia (hypoxia) and/or reperfusion (reoxygenation) induces various forms of cellular and structural damage. A major cause of damage is local inflammatory responses, which may spread to produce more advanced systemic inflammation. Management of I-R injury relies primarily on supportive measures, as specific treatment strategies are lacking. Extracellular vesicles (EVs) are cell-secreted nano-scale structures containing various biomolecules involved in cell communication and multiple physiological processes. EVs derived from certain cell types have been shown to exhibit anti-inflammatory, antioxidant, and angiogenic properties. This review provides an overview of EV-based therapeutics for I-R injury in kidneys, liver, heart, lungs, and brain. Additionally, the mechanisms by which EVs protect against I-R injury are discussed. Promising preclinical findings highlight the potential clinical use of EVs for I-R injury.

摘要

随着缺血再灌注(I-R)损伤的发病率显著增加,迫切需要开发有效的策略来治疗这一全球性健康问题。I-R 损伤可影响所有器官,并与高发病率和死亡率相关。心肌梗死、中风、失血性休克和实体器官移植等病理情况特别容易引起 I-R 损伤。缺血(缺氧)和/或再灌注(再氧合)引起各种形式的细胞和结构损伤。损伤的一个主要原因是局部炎症反应,它可能会扩散到产生更高级别的全身炎症。I-R 损伤的治疗主要依赖于支持性措施,因为缺乏特定的治疗策略。细胞外囊泡(EVs)是细胞分泌的纳米级结构,包含参与细胞通讯和多种生理过程的各种生物分子。已经证明某些细胞类型来源的 EVs 具有抗炎、抗氧化和血管生成特性。本综述概述了用于肾脏、肝脏、心脏、肺和大脑 I-R 损伤的基于 EV 的治疗方法。此外,还讨论了 EV 保护免受 I-R 损伤的机制。有前途的临床前研究结果强调了 EV 在 I-R 损伤中的潜在临床应用。

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