Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles

Abstract

Secreted membrane-enclosed vesicles, collectively called extracellular vesicles (EVs), which include exosomes, ectosomes, microvesicles, microparticles, apoptotic bodies and other EV subsets, encompass a very rapidly growing scientific field in biology and medicine. Importantly, it is currently technically challenging to obtain a totally pure EV fraction free from non-vesicular components for functional studies, and therefore there is a need to establish guidelines for analyses of these vesicles and reporting of scientific studies on EV biology. Here, the International Society for Extracellular Vesicles (ISEV) provides researchers with a minimal set of biochemical, biophysical and functional standards that should be used to attribute any specific biological cargo or functions to EVs.

Keywords: ectosomes; exosomes; extracellular RNA; extracellular vesicles; microparticles; microvesicles.

Fig. 1

Comparative evolution of the use of different terms for EVs in the literature. An advanced search was performed in PubMed at the end of December 2013 to find, for each year of publication, all articles using the given term (singular or plural) as text word: exosome(s), microvesicles, oncosome(s), ectosome(s), prostasome(s), matrix/calcifying vesicle(s). Year of final publication (and not advanced online date) of articles in English (and not other languages) was taken into account. Manual elimination of articles describing non-EV-related work was performed for exosome(s) (RNA-excision machinery) and microvesicle(s) (intracellular secretory vesicles). Use of the term microparticle(s) could not be reliably evaluated, since it is massively used to refer to non-vesicle-related particles. Notably, from 2004 onwards, the term “exosome” has become the most often used in published articles describing EVs, whereas the term “extracellular vesicles,” chosen as generic term at creation of ISEV in September 2011, is steadily growing. This figure is not intended to show expansion of the EV field as compared to other fields, since numbers are not normalized to the total number of scientific medico-biological publications per year.