Rigor and standardization of extracellular vesicle research: Paving the road towards robustness (original) (raw)

2020, Journal of Extracellular Vesicles

Accompanying the growing awareness that extracellular vesicles (EVs) are useful for diagnostics and therapeutics is the realization that EV applications must be established with rigor, reproducibility, and standardization. The small size and heterogeneity of most EVs are well-known barriers to rigorous studies. However, progress is also hampered by the largely unknown influence of a host of pre-analytical variables and a lack of quality controls, differences in EV separation and characterization techniques (van Deun et al., 2017), a general lack of dedicated reference materials and standards (Welsh et al., 2020), and analyses that are poorly defined and thus irreproducible. The goal of this Editorial is to summarize the past, present, and future contributions of the International Society for Extracellular Vesicles (ISEV) to improving rigor and standardization in EV research. We highlight in particular the Rigor and Standardization Subcommittee and the recently published results of a survey on the methods used for separation and characterization of EVs (Royo, Théry, Falcón-Pérez, Nieuwland, & Witwer, 2020). Major challenges remain. Even so, we predict that within a few years, the expansion of an ISEV infrastructure dedicated to rigor and standardization will enable us to turn the ugly duckling of current challenges into a beautiful swan of comparable and reproducible EV measurement results. Because we are working in a new and developing field of research, ISEV has the unique opportunity to set high standards for rigor, and we may even lead the way for other research fields and societies. Rigor and standardization with community input have been part of the ISEV mission since its founding. Impetus for founding a society arose with a 2011 meeting in Paris that was organized by Clotilde Théry and Graça Raposo. The incipient community voted to emphasize ' extracellular vesicles' in the name of the society rather than limiting focus to specific subtypes of EVs. Following the first annual meeting of ISEV in 2012, the first ISEV Workshop was organized and held in October, 2012 in New York City. This Workshop gave rise to the first two ISEV position papers, on standardization of sample collection and processing (Witwer et al., 2013) and RNA analysis (Hill et al., 2013). Subsequent workshops and co-sponsored events have given birth to additional position papers and other products, most of them published in the