CIC bioGUNE
Published November 8, 2019 | Version v1
Journal article Open

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

Creators

  • 1. Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;
  • 2. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA;
  • 3. Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; cDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • 4. Department of Molecular and Translational Medicine, Università degli Studi di Brescia, CSGI and INSTM, Brescia, Italy;
  • 5. Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
  • 6. Cardiff University, School of Medicine, Cardiff, UK;
  • 7. Division of Pharmaceutics and Pharmacology, College of Pharmacy, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA;
  • 8. University of Virginia, Charlottesville, VA, USA;
  • 9. Exosomes laboratory and Metabolomics Platform, CIC bioGUNE, CIBERehd, Bizkaia, Spain; IKERBASQUE, Basque Foundation for Science, Bizkaia, Spain;
  • 10. Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
  • 11. Department of Microbiology and Immunology, Loyola University Chicago, Chicago, IL, USA;
  • 12. School of Biological and Healthy Sciences, Technological University Dublin, Dublin, Ireland;
  • 13. Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Clinical Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China;
  • 14. Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA;
  • 15. Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
  • 16. INSERM U932, Institut Curie, PSL Research University, France;
  • 17. Department of Pediatrics, University of California San Diego, La Jolla, CA, USA;
  • 18. Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway;
  • 19. Program in Molecular and Integrative Physiological Sciences Departments of Environmental Health, Genetics & Complex Diseases Harvard T.H. Chan School of Public Health, Boston, MA, USA;
  • 20. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA;
  • 21. INBIRS Institute, UBA-CONICET School of Medicine University of Buenos Aires, Buenos Aires, Argentina
  • 22. CNR Institute of Neuroscience, Milan, Italy
  • 23. Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • 24. Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway
  • 25. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA
  • 26. Department of Chemistry, Shaw University, Raleigh, NC, USA;
  • 27. Institute for Psychiatry and Neuroscience of Paris, INSERM U1266, Hopital Saint-Anne, Université Descartes, Paris, France;
  • 28. VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium;
  • 29. VIB Center for Inflammation Research, Ghent, Belgium;
  • 30. Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  • 31. Rudolf Virchow Center, Julius-Maximilians-Universität Würzburg, Würzburg, Germany;
  • 32. School of Pharmaceutical Sciences, Tsinghua University-Peking University Joint Center for Life Sciences, Tsinghua University, Beijing, China;
  • 33. Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK;
  • 34. Laboratory of Clinical Chemistry and Haematology & Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

Description

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.

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