In recent years, many researchers have started paying attention to tiny membranous bags, called "extracellular vesicles", which are secreted by cells and are filled with all sorts of biomolecules. Just as there are numerous types of cells in our body, so can extracellular vesicles exhibit diverse molecular and physical traits. Some of them might be just waste shed from cells, while some might be secreted for a certain purpose. This uncertainty is precisely why researchers study extracellular vesicles.

In a new research article published in the Journal of Extracellular Vesicles, platelets were shown to be capable of fine-tuning their extracellular vesicles by adjusting the biomolecular cargo packaged within. This process is now proposed to have a role in communication with macrophages such that these immune cells "take orders" from activated platelets busy stopping bleeding or reacting to other inflammatory signals. These results came from a fruitful collaboration initiated by Pia Siljander’s lab at the University of Helsinki and where Yuya Hayashi from MBG/iNANO contributed the first visual evidence of the link between platelet-derived extracellular vesicles and macrophages in live zebrafish embryos. The zebrafish was used as a vertebrate model system for the study since it allows the researchers to observe the dynamic interplay in real blood circulation, something that cannot be done in humans or mice.

"The field of extracellular vesicle research is still immature when it comes to communication between cells," says Yuya Hayashi. "This is because a lot has been done in single cell culture systems, especially in cancer cell lines, and not much is understood regarding how physiological extracellular vesicles home in on their target cells in a complex tissue environment where most cells represent off-targets. We were very surprised to see that platelet-derived extracellular vesicles are captured so effectively by macrophages among other cells."

"There remain many open questions," adds Pia Siljander, "and this is only the beginning of an inspiring endeavour to dissect the precise molecular mechanisms that make such a fine-tuned communication possible. Yuya and I are discussing the next step, as we're excited that zebrafish share so many relevant genes with humans and they can stop bleeding just like us humans!"

The research was carried out with assistance of the zebrafish facility, headed by Dr. Kasper Kjær-Sørensen and Prof. Claus Oxvig at MBG, Aarhus University.

The scientific article:

Beyond basic characterization and omics: Immunomodulatory roles of platelet-derived extracellular vesicles unveiled by functional testing. Mari Palviainen, Johanna Puutio, Rikke Halse Østergaard, Johannes A. Eble, Katariina Maaninka, Umar Butt, Joseph Ndika, Otto K. Kari, Masood Kamali-Moghaddam, Kasper Kjaer-Sorensen, Claus Oxvig, Ana M. Aransay, Juan M. Falcon-Perez, Antonio Federico, Dario Greco, Saara Laitinen, Yuya Hayashi, Pia R.-M. Siljander. Journal of Extracellular Vesicles 13 (2024). https://doi.org/10.1002/jev2.12513
 

SUPPLEMENTARY INFORMATION

We strive to ensure that all our articles live up to the Danish universities' principles for good research communication. Against this background, the article is supplemented with the following information:

Study type:
Research article

External funding:
The Danish arm of research was supported by Novo Nordisk Foundation (NNF21OC0067359).

Conflicts of interest:
None

More information:
Associate Professor Yuya Hayashi
Department of Molecular Biology and Genetics
& Interdisciplinary Nanoscience Center (iNANO)
Aarhus University, Denmark
yuya.hayashi@mbg.au.dk

Group webpage: https://mbg.au.dk/yuya-hayashi/​​​​​​​

Senior University Lecturer Pia Siljander
Faculty of Biological and Environmental Sciences
University of Helsinki, Finland
pia.siljander@helsinki.fi