The biology, function, and biomedical applications of exosomes.
The biology, function, and biomedical applications of exosomes.
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DOI：
10.1126/science.aau6977
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发表时间：
2020-02-07
期刊：
影响因子：
--
通讯作者：
LeBleu VS
中科院分区：
文献类型：
--
作者：
Kalluri R;LeBleu VS
对细胞外小泡(EVS)的研究有可能识别未知的细胞和分子机制，如细胞间通讯、器官内稳态和疾病。Exosome是EVS的一个子集，平均直径约100纳米。外切体的生物发生涉及到它们起源于内切体，随后与细胞内其他囊泡和细胞器的相互作用产生了外切体的最终内容。它们的不同成分包括核酸、蛋白质、脂类、氨基酸和代谢物，这可以反映它们的细胞起源。在各种疾病中，外切体提供了一个了解细胞或组织状态改变的窗口，而在生物液中检测它们可能提供一个多组分的诊断读数。通过外切体有效地交换细胞成分，可以使它们在设计基于外切体的疗法中得到应用。所有的细胞，原核生物和真核细胞，都会释放细胞外小泡(EVS)，这是它们正常生理和后天异常的一部分。EVS大致可分为两类，胞外体和胞外体。胞外体是通过向外萌发将质膜表面掐掉的囊泡，包括直径约50 nm至1μm的微泡、微粒和大小泡。外切小体是直径在~40~160 nm(平均~100 nm)范围内的肠上皮细胞，起源于内体。质膜的连续内陷最终导致多泡小体的形成，这些小体可以与细胞内的其他小泡和细胞器相交，从而导致外体成分的多样性。根据来源细胞的不同，EVS，包括外周小体，可能含有细胞的许多成分，包括DNA、RNA、脂类、代谢物以及胞浆和细胞表面蛋白。产生外切体的生理目的在很大程度上仍不清楚，需要研究。一种推测的作用是，外切体可能会从细胞中移除多余和/或不必要的成分，以维持细胞内环境的稳定。最近综述的研究还表明，外切体中特定的细胞成分在功能上、靶向的、机制驱动下积累，表明它们在调节细胞间通讯方面具有作用。外切体与免疫反应、病毒致病性、妊娠、心血管疾病、中枢神经系统相关疾病和癌症进展有关。蛋白质、代谢物和核酸由外切体输送到受体细胞中，有效地改变了它们的生物反应。这种外切体介导的反应可以促进疾病或抑制疾病。外切体在调节复杂的细胞内途径方面的内在特性使其在许多疾病的治疗控制中具有潜在的应用价值，包括神经退行性疾病和癌症。外切体可以被设计成输送不同的治疗有效载荷，包括短干扰RNA、反义寡核苷酸、化疗药物和免疫调节剂，并能够将其输送到所需的靶点。外切体的脂质和蛋白质组成可以影响其药代动力学特性，其天然成分可能在提高生物利用度和减少不良反应方面发挥作用。除了它们的治疗潜力外，外切体还具有帮助疾病诊断的潜力。据报道，它们存在于所有生物体液中，通过对生物体液(液体活组织检查)的采样，可以很容易地获得外切体的复杂货物的组成。基于Exosome的液体活组织检查突出了它们在癌症和其他疾病患者的诊断和判断预后方面的潜在价值。疾病进展和对治疗的反应也可以通过对外切体的多组分分析来确定。外切体的研究是一个活跃的研究领域。正在进行的技术和实验进步可能会产生关于它们的异质性和生物学功能的有价值的信息(S)，并增强我们利用它们的治疗和诊断潜力的能力。随着我们开发更多标准化的纯化和分析方法来研究外切体，这可能会揭示它们的功能异质性。尽管如此，使用丰富的外切体EV的功能读数已经为它们在各种疾病中的贡献提供了新的见解。在健康和疾病中，具有从头产生或诱导产生细胞特异性外切体的新的遗传小鼠模型可能会显示外切体在局部和器官之间的细胞间交流中的因果作用。外切体的产生和含量是否随着年龄的变化而变化需要研究，这些信息可以为组织衰老、器官退化以及程序性或早衰提供新的见解。EVS和/或Exosome是否先于地球上第一个单细胞有机体的出现引起了人们的猜测，未来有重点的生物电学和生物化学实验可能会揭示它们独立于细胞的生物学功能。单外切体鉴定和分离以及冷冻电子显微镜分析有可能极大地提高我们对外切体的基本生物学及其在应用科学和技术中的应用的理解。这些知识将为外切体治疗各种疾病的潜力提供信息，包括癌症和神经退行性疾病。外体：人体内一种细胞到细胞的运输系统，具有多效性。胞外体是由所有细胞产生的胞外小泡，它们携带核酸、蛋白质、脂类和代谢物。它们是健康和疾病中近距离和远距离细胞间通讯的媒介，影响细胞生物学的各个方面。
The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics. All cells, prokaryotes and eu-karyotes, release extracellular vesicles (EVs) as part of their normal physiology and during acquired abnormalities. EVs can be broadly divided into two categories, ectosomes and exosomes. Ectosomes are vesicles that pinch off the surface of the plasma membrane via outward budding, and include microvesicles, microparticles, and large vesicles in the size range of ~50 nm to 1 μm in diameter. Exosomes are EVs with a size range of ~40 to 160 nm (average ~100 nm) in diameter with an endosomal origin. Sequential invagination of the plasma membrane ultimately results in the formation of multivesicular bodies, which can intersect with other intracellular vesicles and organelles, contributing to diversity in the constituents of exosomes. Depending on the cell of origin, EVs, including exosomes, can contain many constituents of a cell, including DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins. The physiological purpose of generating exosomes remains largely unknown and needs investigation. One speculated role is that exosomes likely remove excess and/or unnecessary constituents from cells to maintain cellular homeostasis. Recent studies reviewed here also indicate a functional, targeted, mechanism-driven accumulation of specific cellular components in exosomes, suggesting that they have a role in regulating intercellular communication. Exosomes are associated with immune responses, viral pathogenicity, pregnancy, cardiovascular diseases, central nervous system-related diseases, and cancer progression. Proteins, metabolites, and nucleic acids delivered by exosomes into recipient cells effectively alter their biological response. Such exosome-mediated responses can be disease promoting or restraining. The intrinsic properties of exosomes in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases, including neurodegenerative conditions and cancer. Exosomes can be engineered to deliver diverse therapeutic payloads, including short interfering RNAs, antisense oligonucleotides, chemotherapeutic agents, and immune modulators, with an ability to direct their delivery to a desired target. The lipid and protein composition of exosomes can affect their pharmacokinetic properties, and their natural constituents may play a role in enhanced bioavailability and in minimizing adverse reactions. In addition to their therapeutic potential, exosomes also have the potential to aid in disease diagnosis. They have been reported in all biological fluids, and the composition of the complex cargo of exosomes is readily accessible via sampling of biological fluids (liquid biopsies). Exosome-based liquid biopsy highlights their potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. Disease progression and response to therapy may also be ascertained by a multicomponent analysis of exosomes. The study of exosomes is an active area of research. Ongoing technological and experimental advances are likely to yield valuable information regarding their heterogeneity and biological function(s), as well as enhance our ability to harness their therapeutic and diagnostic potential. As we develop more standardized purification and analytical procedures for the study of exosomes, this will likely reveal their functional heterogeneity. Nonetheless, functional readouts using EVs enriched for exosomes have already provided new insights into their contribution to various diseases. New genetic mouse models with the ability for de novo or induced generation of cell-specific exosomes in health and disease will likely show the causal role of exosomes in cell-to-cell communication locally and between organs. Whether exosome generation and content change with age needs investigation, and such information could offer new insights into tissue senescence, organ deterioration, and programmed or premature aging. Whether EVs and/or exosomes preceded the first emergence of the single-cell organism on the planet is tempting to speculate, and focused bioelectric and biochemical experiments in the future could reveal their cell-independent biological functions. Single-exosome identification and isolation and cryoelectron microscopy analyses have the potential to substantially improve our understanding of the basic biology of exosomes and their use in applied science and technology. Such knowledge will inform the therapeutic potential of exosomes for various diseases, including cancer and neurodegenerative diseases. Exosomes: A cell-to-cell transit system in the human body with pleiotropic functions. Exosomes are extracellular vesicles generated by all cells and they carry nucleic acids, proteins, lipids, and metabolites. They are mediators of near and long-distance intercellular communication in health and disease and affect various aspects of cell biology.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
64.5
作者：
Boelens MC;Wu TJ;Nabet BY;Xu B;Qiu Y;Yoon T;Azzam DJ;Twyman-Saint Victor C;Wiemann BZ;Ishwaran H;Ter Brugge PJ;Jonkers J;Slingerland J;Minn AJ
通讯作者：
Minn AJ
影响因子：
5.4
作者：
Altan-Bonnet N
通讯作者：
Altan-Bonnet N
影响因子：
5.2
作者：
Abd Elmageed, Zakaria Y.;Yang, Yijun;Thomas, Raju;Ranjan, Manish;Mondal, Debasis;Moroz, Krzysztof;Fang, Zhide;Rezk, Bashir M.;Moparty, Krishnarao;Sikka, Suresh C.;Sartor, Oliver;Abdel-Mageed, Asim B.
通讯作者：
Abdel-Mageed, Asim B.
影响因子：
4
作者：
Baker, Sian;Polanco, Juan Carlos;Gotz, Jurgen
通讯作者：
Gotz, Jurgen