Eavesdropping on extracellular vesicles

A rapidly evolving toolbox is helping researchers to get a handle on the biological and functional diversity of these ubiquitous — but still somewhat enigmatic — cell-secreted nanoparticles.

The pH-responsive fluorescent dye pHluorin_M153R-CD63 makes it possible to visualize EVs upon their release from cells. Credit: Bong Hwan Sung, Weaver lab, Vanderbilt University

As recently as 20 years ago, researchers working on extracellular vesicles routinely struggled to convince their colleagues of the biological importance of these tiny membrane-bound bubbles.

“We met so many skeptical people in everyday life, at meetings: ‘Are they real? Are they just artifacts?’,” says Edit Buzás of Semmelweis University in Budapest. This was despite the fact that scientists had been describing such vesicles since the 1960s, and assigning biological activity to them since the 1980s. “A lot of people were saying that I was kind of a ‘proctologist of the cell’,” jokes Guillaume van Niel of INSERM in Paris, France. “But I didn’t care …. I was one of the first to be able to see them by electron microscopy, so I could prove they do exist, and they certainly have a role.”

Time has proven the skeptics wrong. Today, extracellular vesicles (EVs) are the focus of a vibrant field, with labs around the world striving to understand why and how cells release these tiny particles, as well as the physiological impact of the proteins, nucleic acids and other biomolecules contained within. There is already considerable evidence that EVs can facilitate cell-to-cell communication in various settings, wherein vesicles discharged by one cell travel through the circulation — potentially over considerable distances — only to be taken up and ‘decoded’ by recipients elsewhere in the body.