Clinical uses of cellular communication Exosomes are a type of extracellular vesicle that contain constituents (protein, DNA, and RNA) of the cells that secrete them. They are taken up by distant cells, where they can affect cell function and behavior. Intercellular communication through exosomes seems to be involved in the pathogenesis of various disorders, including cancer, neurodegeneration, and inflammatory diseases. In a Review, Kalluri and LeBleu discuss the biogenesis and function of exosomes in disease, highlighting areas where more research is needed. They also discuss the potential clinical applications of exosome profiling for diagnostics and exosome-mediated delivery of therapeutics to target disease cells. Science, this issue p. eaau6977 BACKGROUND All cells, prokaryotes and eukaryotes, 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. ADVANCES 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. OUTLOOK 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. 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.

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外泌体的生物学、功能和生物医学应用

细胞通讯的临床应用 外泌体是一种细胞外囊泡，含有分泌它们的细胞成分（蛋白质、DNA 和 RNA）。它们被远处的细胞吸收，在那里它们可以影响细胞的功能和行为。通过外泌体的细胞间通讯似乎参与了各种疾病的发病机制，包括癌症、神经变性和炎症性疾病。在一篇综述中，Kalluri 和 LeBleu 讨论了外泌体在疾病中的生物发生和功能，强调了需要更多研究的领域。他们还讨论了外泌体分析在诊断和外泌体介导的靶向疾病细胞治疗方面的潜在临床应用。科学，这个问题 p。eaau6977 背景所有细胞，原核生物和真核生物，释放细胞外囊泡 (EV) 作为其正常生理机能和获得性异常的一部分。EVs可以大致分为两类，外泌体和外泌体。外泌体是通过向外出芽夹住质膜表面的囊泡，包括直径约 50 nm 至 1 μm 的微囊泡、微粒和大囊泡。外泌体是直径范围为 ~40 至 160 nm（平均 ~100 nm）且具有内体起源的 EV。质膜的连续内陷最终导致多囊泡体的形成，多囊泡体可以与其他细胞内囊泡和细胞器相交，有助于外泌体成分的多样性。根据起源细胞的不同，EVs（包括外泌体）可以包含细胞的许多成分，包括 DNA、RNA、脂质、代谢物，以及细胞溶质和细胞表面蛋白质。产生外泌体的生理目的在很大程度上仍然未知，需要研究。一种推测的作用是外泌体可能会从细胞中去除多余和/或不必要的成分以维持细胞稳态。这里综述的最新研究还表明，外泌体中特定细胞成分的功能性、靶向性、机制驱动的积累，表明它们在调节细胞间通讯中发挥作用。进展 外泌体与免疫反应、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。外泌体递送到受体细胞中的蛋白质、代谢物和核酸有效地改变了它们的生物反应。这种外泌体介导的反应可以促进或抑制疾病。外泌体在调节复杂细胞内通路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。外泌体可以被设计为递送多种治疗有效载荷，包括短干扰 RNA、反义寡核苷酸、化疗剂和免疫调节剂，并能够将它们递送至所需的靶标。外泌体的脂质和蛋白质组成会影响它们的药代动力学特性，它们的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，外泌体还具有帮助疾病诊断的潜力。它们在所有生物体液中都有报道，并且外泌体的复杂货物的组成很容易通过生物体液取样（液体活检）获得。基于外泌体的液体活检突出了它们在诊断和确定癌症和其他疾病患者预后方面的潜在用途。疾病进展和对治疗的反应也可以通过外泌体的多组分分析来确定。展望外泌体的研究是一个活跃的研究领域。持续的技术和实验进步可能会产生有关其异质性和生物学功能的宝贵信息，并增强我们利用其治疗和诊断潜力的能力。随着我们为外泌体研究开发更标准化的纯化和分析程序，这可能会揭示它们的功能异质性。尽管如此，使用富含外泌体的 EV 的功能读数已经为它们对各种疾病的贡献提供了新的见解。具有在健康和疾病中从头或诱导产生细胞特异性外泌体能力的新遗传小鼠模型可能会显示外泌体在局部和器官之间的细胞间通讯中的因果作用。外泌体的生成和内容是否随着年龄的增长而变化需要调查，这些信息可以为组织衰老、器官退化以及程序性或过早衰老提供新的见解。EV 和/或外泌体是否在地球上首次出现单细胞生物之前存在，这很容易推测，未来的重点生物电和生化实验可以揭示它们独立于细胞的生物学功能。单外泌体鉴定和分离以及冷冻电子显微镜分析有可能大大提高我们对外泌体基本生物学及其在应用科学和技术中的应用的理解。这些知识将为外泌体对各种疾病的治疗潜力提供信息，包括癌症和神经退行性疾病。外泌体：人体内具有多效功能的细胞间转运系统。外泌体是所有细胞产生的细胞外囊泡，它们携带核酸、蛋白质、脂质和代谢物。它们是健康和疾病中近距离和远距离细胞间通讯的介质，并影响细胞生物学的各个方面。细胞外囊泡 (EV) 的研究有可能确定细胞间通讯以及器官稳态和疾病中未知的细胞和分子机制。平均直径约为 100 纳米的外泌体是 EV 的一个子集。外泌体的生物发生涉及其起源于内体，随后与其他细胞内囊泡和细胞器的相互作用产生外泌体的最终成分。它们的不同成分包括核酸、蛋白质、脂质、氨基酸和代谢物，可以反映它们的细胞来源。在各种疾病中，外泌体提供了一个了解细胞或组织状态改变的窗口，它们在生物体液中的检测可能提供多组分诊断读数。