Circulating extracellular vesicles in human disease

It is well known that cells release fluid-filled sacs (vesicles) to the extracellular environment during cell death, or apoptosis, but it has been increasingly recognized that healthy cells may also release vesicles in the process of normal functions. Vesicles that are released by healthy cells have a wide variety of names (e.g., ectosomes, microparticles, microvesicles, exosomes, and oncosomes), with the term "extracellular vesicles" typically used as a generic reference to secreted vesicles. Extracellular vesicles are found in circulation and contain cell-derived biomolecules (e.g., RNA, protein, and metabolites). Extracellular vesicles are implicated in trafficking of molecules between cells and as such have an effect on physiologic function and serve as biomarkers for disease (see video). Nevertheless, important limitations - including practical difficulties in assaying low concentrations of extracellular vesicles in circulation, identifying their tissue of origin, and specifying which molecular cargo is most relevant - have restrained enthusiasm for research into the role of extracellular vesicles in vivo. The goal of this article is to provide a brief introduction to extracellular vesicles, with a specific focus on translational and clinical studies to highlight emerging evidence that suggests a potential role in human disease. Given the explosion of work in this field, it is difficult to cover the breadth of diseases in which extracellular vesicles may be functionally relevant. As such, the reader is referred to the expanding literature in this field for more details.