Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States.
Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States.
Adv Clin Chem. 2021;102:63-125. doi: 10.1016/bs.acc.2020.08.010. Epub 2020 Oct 1.
Extracellular vesicles (EV) are defined as nanosized particles, with a lipid bilayer, that are unable to replicate. There has been an exponential increase of research investigating these particles in a wide array of diseases and deleterious states (inflammation, oxidative stress, drug-induced liver injury) in large part due to increasing recognition of the functional capacity of EVs. Cells can package lipids, proteins, miRNAs, DNA, and RNA into EVs and send these discrete packages of molecular information to distant, recipient cells to alter the physiological state of that cell. EVs are innately heterogeneous as a result of the diverse molecular pathways that are used to generate them. However, this innate heterogeneity of EVs is amplified due to the diversity in isolation techniques and lack of standardized nomenclature in the literature making it unclear if one scientist's "exosome" is another scientist's "microvesicle." One goal of this chapter is to provide the contextual understanding of EV origin so one can discern between divergent nomenclature. Further, the chapter will explore the potential protective and harmful roles that EVs play in DILI, and the potential of EVs and their cargo as a biomarker. The use of EVs as a therapeutic as well as a vector for therapeutic delivery will be discussed.
细胞外囊泡(EV)被定义为纳米级颗粒,具有脂质双层,不能复制。由于越来越多的人认识到 EV 的功能能力,因此研究这些颗粒在广泛的疾病和有害状态(炎症、氧化应激、药物性肝损伤)中的作用呈指数级增长。细胞可以将脂质、蛋白质、miRNA、DNA 和 RNA 包装到 EV 中,并将这些离散的分子信息包发送到远处的受体细胞,以改变该细胞的生理状态。由于用于生成 EV 的分子途径多种多样,因此 EV 天生具有异质性。然而,由于分离技术的多样性以及文献中缺乏标准化的命名法,导致 EV 的这种固有异质性加剧,使得不清楚一位科学家的“外泌体”是否是另一位科学家的“微泡”。本章的一个目标是提供 EV 起源的背景理解,以便能够区分不同的命名法。此外,本章将探讨 EV 在 DILI 中发挥的潜在保护和有害作用,以及 EV 及其货物作为生物标志物的潜力。还将讨论 EV 作为治疗手段以及作为治疗性递药载体的应用。