The use of exosomes in clinical settings is progressively becoming a reality, as clinical trials testing exosomes for diagnostic and therapeutic applications are generating remarkable interest from the scientific community and investors. Exosomes are small extracellular vesicles secreted by all cell types playing intercellular communication roles in health and disease by transferring cellular cargoes such as functional proteins, metabolites and nucleic acids to recipient cells. An in-depth understanding of exosome biology is therefore essential to ensure clinical development of exosome based investigational therapeutic products. Here we summarise the most up-to-date knowkedge about the complex biological journey of exosomes from biogenesis and secretion, transport and uptake to their intracellular signalling. We delineate the major pathways and molecular players that influence each step of exosome physiology, highlighting the routes of interest, which will be of benefit to exosome manipulation and engineering. We highlight the main controversies in the field of exosome research: their adequate definition, characterisation and biogenesis at plasma membrane. We also delineate the most common identified pitfalls affecting exosome research and development. Unravelling exosome physiology is key to their ultimate progression towards clinical applications.

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外泌体之旅：从生物发生到摄取和细胞内信号传导

外泌体在临床环境中的使用正逐渐成为现实，因为测试外泌体用于诊断和治疗应用的临床试验引起了科学界和投资者的极大兴趣。外泌体是由所有细胞类型分泌的小的细胞外囊泡，通过将功能蛋白、代谢物和核酸等细胞货物转移到受体细胞，在健康和疾病中发挥细胞间通讯作用。因此，深入了解外泌体生物学对于确保基于外泌体的研究性治疗产品的临床开发至关重要。在这里，我们总结了关于外泌体从生物发生和分泌、运输和摄取到细胞内信号传导的复杂生物学旅程的最新知识。我们描述了影响外泌体生理学每个步骤的主要途径和分子参与者，突出了感兴趣的途径，这将有利于外泌体操作和工程。我们强调外泌体研究领域的主要争议：它们在质膜上的充分定义、表征和生物发生。我们还描述了影响外泌体研究和开发的最常见缺陷。解开外泌体生理学是它们最终走向临床应用的关键。质膜的表征和生物发生。我们还描述了影响外泌体研究和开发的最常见缺陷。解开外泌体生理学是它们最终走向临床应用的关键。质膜的表征和生物发生。我们还描述了影响外泌体研究和开发的最常见缺陷。解开外泌体生理学是它们最终走向临床应用的关键。