Extracellular vesicles – a novel exciting research topic

Portrait GSEV

Extracellular vesicles (EVs) appear to be essential parts of an ancient intercellular communication system we just become aware of. According to our current thinking, cells can assemble lipids, proteins and nucleic acids in specific combinations to nano-sized vesicles being released into their extracellular environment. At least, a proportion of such EVs seems to send complex information to neighboring cells as well as to cells in distant tissues. Although the principle may appear new for many of the readers initially, we are pretty aware of cell-derived compositions of lipids, proteins and nucleic acids, which have severe impacts on cells, organisms and even human societies, namely viruses.
Upon studying EVs, we have learned that their share many features with viruses. In this context, it has been considered that at least some of the viruses, e.g. lentiviruses, may represent malignant EVs. Indeed, if EVs represent parts of an ancient communication system, it appears very likely that they have been captured by pathogens. Thinking in this direction it may explain why EV researchers are so much excited about the new research field. If we understand how intercellular signaling mediating EVs are assembled and how they transmit their information to selected target cells, as viruses for example do, EVs may become a very powerful tool in different branches of life sciences.
We obtained evidence that EVs are essentially required to control cell communication in physiological and pathophysiological conditions. As EVs seem to be assembled in cell type specific manners, they provide very promising biomarkers for a variety of diseases. In case we understand their target cell selection mechanism, and become able to alter the information they transmit in a controlled manner, or load EVs with active substances, they would be ideal drug delivery vehicles. If we unravel how EVs influence biological processes, we may use EVs to counteract pathophysiological processes and apply them as therapeutic agents. They might also serve as a novel class of vaccines, or get important tools for many other applications. I hope that this special issue will provide a comprehensive overview over the field of EVs and that it transports some of the enthusiasm that we share within the EV community.
Despite our passion, we need to admit that we are just at the beginning of a very promising research area. There are many hurdles, which we have to deal with. Although we have learned to work with viruses, it is challenging to investigate non-pathologic, biological nanoparticles. They are too small to be detected by light microscopy and so we need special platforms to analyze them in detail. Originally, exosomes, a special class of EVs, were discovered by electron microscopy in 1983. Later on, crude preparation technologies were used to enrich them and to study their biological properties and functions, e.g. differential centrifugation protocols, which in an ultracentrifugation step allow to precipitate small EVs of sizes between 70-150 nm. Many groups have characterized and still characterize the content of ultracentrifuge-pelleted material which for sure contains EVs, but also a huge collection of non-EV associated byproducts.
With the development of new analysis tools and gaining more and more knowledge in the field, we have to learn that many of the previous methods are not specific for EVs and co-prepare or co-analyze nanoparticles of comparable sizes which lack any EV characteristics. Accordingly, and despite the fact that there is an exponentially increasing amount of publications about EVs, the field mainly progresses in recognizing its own limitations and by solving various technical challenges.
Since these challenges are not as effectively reported as strong effects, and since many negative findings remain unpublished, it is hard for interested persons to recognize the true current state-of-the-art in the field. To address these issues, EV societies have been formed in which experts discuss the progress and challenges in the field and try to summarize it in several position papers, many of them being published in the Journal for Extracellular Vesicles (JEV), which is released by the International Society of Extracellular Vesicles (ISEV) founded in 2012. One of the recent papers is the report of the Minimal information for studies of extracellular vesicles 2018 (MISEV2018) which is written by almost 400 authors and comprises more than 40 pages of condensed information.
Thinking that it is of uppermost importance to communicate the current state of the art and understanding that getting an appropriate overview over the field is challenging itself, and many researchers approaching the EV field may not be able to participate on international EV meetings, we have founded the German Society for Extracellular Vesicles (GSEV). The GSEV is intended to provide a national platform to support scientists working in Germany to step into the field and provide appropriate discussion platforms for novel as well as experienced EV researcher. For now, the GSEV organizes two meetings a year:
• our Annual Meeting in spring, a shared meeting with the Interdisziplinäre Gruppe für Labor und Durchflusszytometrie (IGLD), Instand, the German Stem Cell Network (GSCN) and the Dachverband für Technologen/-innen und Analytiker/-innen in der Medizin Deutschland (DVA).
• our Autumn Meeting co-organized with other national EV societies from Europe, such as the Austrian Society of Extracellular Vesicles (ASEV) and the UK Society for Extracellular Vesicles
At both meetings, we team-up with specialists in clinical diagnostics, hematologists, transfusion medicals and therapists, to provide a unique platform to promote translational EV research. In addition, EV-related workshops are organized with industry experts in the EV field.
To provide an overview over the field, we have decided to publish and distribute this collection of some aspects and research topics within the EV field, highlighting both, many promising themes but also challenges in the field. We hope that this special EV issue attracts further researchers to actively approach the EV field and provides an interesting reading for anyone who is curious in this exciting field of life sciences.

Bernd Giebel
On behalf of the board of the German Society for Extracellular Vesicles