EVs are small vesicles secreted by almost all cell types. They are surrounded by a membrane similar to the cell membrane and contain proteins and RNA, i.e. transcripts of the genetic code as building instructions for further proteins. With a size of only 50 nanometres to a few micrometres, they can easily move through the body. In principle, a kind of cellular message in a bottle.

The appeal of EVs is simply explained. They offer science unprecedented insights into communication between cells, the smallest living units in our bodies. What’s more, communication can not only be observed and decoded, but also mimicked. For medicine, this means new possibilities to intervene in the course of diseases or to set certain desired processes in motion. In a way, EVs as therapeutics would also be a further development of cell therapies. Instead of applying cells in order to use their positive signals – for example the anti-inflammatory effect of mesenchymal stem cells – EVs could be used to apply the signals themselves. Compared to cells, which like all living things can self-replicate and change their behaviour, EVs are static. Once delivered, they contain a clear message that does not change.

EVs have been observed in important processes such as immune defence, regeneration, as well as in the maintenance of the natural balance within a tissue. They also play a role in degenerative diseases and cancer. As a means of communication, they know no good or bad – as with any message, the content makes the difference. Understanding EVs, even in their undesirable forms, helps to better understand the diseases and develop new diagnostic methods.

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Many studies are looking into the biological mechanisms of EVs in order to pave the way for future therapies. Intensive research is also being carried out at the Ludwig Boltzmann Institute of Traumatology (LBI Trauma), the research centre in cooperation with AUVA. But the scientists are not only focusing on cellular mechanisms: With a view to future application in the clinic, quality controls are also an important factor.

Currently, EVs are being studied with a combination of measurements of particle properties, protein composition and adapted cell characterisation methods. For a leap into medical routine, complex scientific methods must be turned into practical, standardised tests.

Together with scientists from the Paracelsus Medical Private University Salzburg and the University of Applied Sciences Upper Austria, Campus Linz, Eleni Priglinger developed a measurement based on the quartz crystal microbalance, a sensor technique that uses the relationship between electrical voltage and mechanical deformation of quartz. Antibodies are anchored on a quartz crystal coated with a lipid layer. According to the key-lock principle, these antibodies “catch” those EVs that carry the corresponding antigen structure on their surface. In addition, this technique can also measure the energy loss (“dissipation”) of the EVs after binding – it provides information about how soft or stiff the measured particle is. EVs that are no longer intact, small particles with the same antigens, or loose proteins are thus detected and can be excluded from the measurement. This distinction between EVs and other non-EV particles is a key advantage that makes the method particularly robust.

Another key advantage is the simplicity of the measurement. It can be carried out without prior staining of the EVs, which reduces the effort required for sample preparation to a minimum. The scientists hope that this will encourage laboratories to expand the spectrum of their methods to include the new EV measurement. A broader infrastructure for testing and quality assurance would be an important step for the leap into clinical routine.

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The importance of thorough characterisation was demonstrated by Johannes Oesterreicher and his colleagues from the Vascular Biology Research Group at LBI Trauma. As a product of natural processes, they are subject to fluctuations – one and the same cell can emit a different spectrum of EVs depending on the situation. These fluctuations can also be observed in cell culture, where conditions are particularly standardised.

The researchers examined vascular cells from the umbilical cord in different situations – such as cell density. In the culture bottle, the cells grow on a plastic surface and multiply until they cover the entire surface in a densely packed manner. Some cell types do not mind this crowding, others react extremely sensitively to it. In vascular cells, large cell densities alter the division rate and the genes that are transcribed from the nucleus and translated into proteins. In the umbilical cord cells, the LBI Trauma scientists have now also been able to show that EV secretion changes. While small vesicles tend to be released when there is enough free space in the bottle, densely packed cells tend to release larger EVs.

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Thanks to the great scientific interest of its members, The Austrian Society for Extracellular Vesicles (ASEV) was founded 6 years ago. Wolfgang Holnthoner, head of vascular biology research at LBI Trauma, has not only recently become the new president of the society, but has also been influential in the community since its inception. In addition to organising events, he was responsible for setting up the ASEV social media channels (on Facebook and Twitter), where news about conferences, publications and more are regularly posted. The exchange with international EV societies is not neglected either. #EVenthusiasts are invited to join the active Twitter bubble.