Exosomes: nanosized cellular messages.

Abstract

Nature has designed clever ways for information and material transfer between cells and for intercellular coordination. Mechanisms include direct cell contact, gap junctions, and receptor-ligand signaling. In the past decade, a particular form of exchange has gained increasing attention, and that is intercellular transfer of extracellular vesicles—natural nanocarriers that deliver biological payloads at long range.1 Article, see p 1312 Many terms have been coined for vesicles found in the extracellular space, including matrix vesicles, extracellular membrane vesicles, microparticles,1 microvesicles,1,2 shedding vesicles,3 plasma membrane-derived vesicles,4 ectosomes,5 exovesicles,6 and exosomes.7 Sometimes these terms are used interchangeably, however, some have been assigned specific distinguishing features, such as size, context, or protein markers. Bone biologists showed decades ago that extracellular vesicles of a certain type, matrix vesicles, are central in skeletal mineralization, where they are thought to serve as a nidus for initiation of hydroxyapatite crystal formation.8 The general view is that matrix vesicles are formed by budding off from the plasma membrane. A leader in the field of matrix vesicle biology, Anderson,9 also identified matrix vesicles in human aortic calcification, one of the first demonstrations that vascular and bone mineralization occur by similar mechanisms. Exosomes, which are distinguished by endosomal marker proteins and their origin from a specialized endosomal pathway, arise in a wide variety of cell types, and serve many functions, such as removal of unwanted stress proteins and coordination of membrane biogenesis. They may have a role in disease processes. The payload of exosomes reportedly may include microRNA, proteins, and viral, bacterial, and prion particles.10–13 Matrix vesicles and exosomes are found in other parts of the natural world. As with the hydroxyapatite mineral of bone, the calcium carbonate mineral encasing shellfish was previously thought to …