Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop

Paracrine and endocrine roles have increasingly been ascribed to extracellular vesicles (EVs) generated by multicellular organisms. Central to the biogenesis, content, and function of EVs are their delimiting lipid bilayer membranes. To evaluate research progress on membranes and EVs, the International Society for Extracellular Vesicles (ISEV) conducted a workshop in March 2018 in Baltimore, Maryland, USA, bringing together key opinion leaders and hands-on researchers who were selected on the basis of submitted applications. The workshop was accompanied by two scientific surveys and covered four broad topics: EV biogenesis and release; EV uptake and fusion; technologies and strategies used to study EV membranes; and EV transfer and functional assays. In this ISEV position paper, we synthesize the results of the workshop and the related surveys to outline important outstanding questions about EV membranes and describe areas of consensus. The workshop discussions and survey responses reveal that while much progress has been made in the field, there are still several concepts that divide opinion. Good consensus exists in some areas, including particular aspects of EV biogenesis, uptake and downstream signalling. Areas with little to no consensus include EV storage and stability, as well as whether and how EVs fuse with target cells. Further research is needed in these key areas, as a better understanding of membrane biology will contribute substantially towards advancing the field of extracellular vesicles. Fil: Russell, Ashley E.. University Johns Hopkins; Estados Unidos Fil: Sneider, Alexandra. University Johns Hopkins; Estados Unidos Fil: Witwer, Kenneth W.. University Johns Hopkins; Estados Unidos Fil: Bergese, Paolo. Università Degli Studi Di Brescia; Italia Fil: Bhattacharyya, Suvendra N.. Indian Institute of Chemical Biology; India Fil: Cocks, Alexander. Cardiff University; Reino Unido Fil: Cocucci, Emanuele. Ohio State University; Estados Unidos Fil: Erdbrügger, Uta. University of Virginia; Estados Unidos Fil: Falcon Perez, Juan M.. Ikerbasque Basque Foundation for Science; España Fil: Freeman, David W.. National Institute On Aging National Institute for Helth ; Estados Unidos Fil: Gallagher, Thomas M.. Loyola University Of Chicago; Estados Unidos Fil: Hu, Shuaishuai. Technological University Dublin; Irlanda Fil: Huang, Yiyao. University Johns Hopkins; Estados Unidos. Southern Medical University; China Fil: Jay, Steven M.. University of Maryland; Estados Unidos Fil: Kano, Shin-ichi. The University of Alabama at Birmingham School of Medicine; Estados Unidos Fil: Lavieu, Gregory. Institut Curie; Francia Fil: Leszczynska, Aleksandra. University of California at San Diego; Estados Unidos Fil: Llorente, Alicia M.. Oslo University Hospital; Noruega Fil: Lu, Quan. Harvard University. Harvard School of Public Health; Estados Unidos Fil: Mahairaki, Vasiliki. University Johns Hopkins; Estados Unidos Fil: Muth, Dillon C.. University Johns Hopkins; Estados Unidos Fil: Noren Hooten, Nicole. National Institute On Aging National Institute for Helth ; Estados Unidos Fil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Prada, Ilaria. Consiglio Nazionale delle Ricerche; Italia Fil: Sahoo, Susmita. Icahn School of Medicine at Mount Sinai ; Estados Unidos Fil: Schøyen, Tine Hiorth. Uit The Arctic University Of Norway; Noruega. University Johns Hopkins; Estados Unidos Fil: Sheng, Lifuy. University of Washington. School of Medicine; Estados Unidos Fil: Tesch, Deanna. Shaw University; Estados Unidos Fil: Van Niel, Guillaume. No especifíca; Fil: Vandenbroucke, Roosmarijn E.. University of Ghent; Bélgica Fil: Verweij, Frederik J.. No especifíca; Fil: Villar, Ana V.. Universidad de Cantabria; España Fil: Wauben, Marca. University of Utrecht; Países Bajos Fil: Wehman, Ann M.. Universität Würzburg; Alemania Fil: Ardavan, Arzhang. Peking University; ; China Fil: Carter, David Raul Francisco. Oxford Brookes University; Reino Unido Fil: Vader, Pieter. University Medical Center Utrecht; Países Bajos