A brief history of nearly EV-erything - The rise and rise of extracellular vesicles

Abstract

Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell-to-cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes. These small biological particles are also deregulated in disease. As we approach the 75th anniversary of the first experiments in which EVs were unknowingly isolated, it seems right to take stock and look back on how the field started, and has since exploded into its current state. Here we review the early experiments, summarise key findings that have propelled the field, describe the growth of an organised EV community, discuss the current state of the field, and identify key challenges that need to be addressed.

Keywords: ectosome; exosome; extracellular vesicle; microparticle; microvesicle.

FIGURE 1

The primary routes of extracellular vesicle biogenesis. Exosomes are released from cells when a multivesicular body (which is formed when an early endosome matures and inwardly buds to form intraluminal vesicles) fuses with the plasma membrane. Ectosomes (more commonly called microvesicles and microparticles) are formed when the plasma membrane buds outwardly and pinches off. Cargo can be loaded into both intraluminal vesicles (which are released as exosomes) and ectosomes. Other types of vesicles such as apoptotic bodies (not shown) can be released by dying cells.

FIGURE 2

Timeline of selected milestones in the EV field