间充质干细胞（MSCs）是维持组织稳态和修复的重要细胞，它们会分泌囊泡到细胞外环境中。已证明分离出来的外泌体对血管生成、免疫调节和组织再生具有影响。为了保证其在临床上的治疗应用，人们已经付出了大量的努力来描述这些细胞外囊泡（EVs）的作用机制并确保其安全。应用MSC源性EVs的主要优势是它们具有低或不存在的免疫原性，因此可用作药物递送或治疗剂，以及用于创面愈合、不同类型的癌症以及神经和心血管系统的炎症过程。MSC源性EVs没有血管阻塞性或明显的不良作用。它们纳米尺寸保证了它们通过血脑屏障，没有细胞毒性或免疫原性作用。已有多项体外实验使用从不同来源获得的EVs来了解它们的生物学、分子成分、信号通路和作用机制。应用EVs于人类治疗最近已成为现实，进行了用于治疗阿尔茨海默病、视网膜退化和COVID-19患者的临床试验。在此，我们描述并比较了不同细胞外囊泡隔离方法和治疗应用，以及它们对组织修复和再生过程的影响，并介绍了最新的临床试验报告。版权所有© 2023 Aguiar Koga，Fernandes，Fratini，Sogayar和Carreira。

Mesenchymal stem cells (MSCs) are crucial for tissue homeostasis and repair, secreting vesicles to the extracellular environment. Isolated exosomes were shown to affect angiogenesis, immunomodulation and tissue regeneration. Numerous efforts have been dedicated to describe the mechanism of action of these extracellular vesicles (EVs) and guarantee their safety, since the final aim is their therapeutic application in the clinic. The major advantage of applying MSC-derived EVs is their low or inexistent immunogenicity, prompting their use as drug delivery or therapeutic agents, as well as wound healing, different cancer types, and inflammatory processes in the neurological and cardiovascular systems. MSC-derived EVs display no vascular obstruction effects or apparent adverse effects. Their nano-size ensures their passage through the blood-brain barrier, demonstrating no cytotoxic or immunogenic effects. Several in vitro tests have been conducted with EVs obtained from different sources to understand their biology, molecular content, signaling pathways, and mechanisms of action. Application of EVs to human therapies has recently become a reality, with clinical trials being conducted to treat Alzheimer's disease, retina degeneration, and COVID-19 patients. Herein, we describe and compare the different extracellular vesicles isolation methods and therapeutic applications regarding the tissue repair and regeneration process, presenting the latest clinical trial reports.Copyright © 2023 Aguiar Koga, Fernandes, Fratini, Sogayar and Carreira.