FedEx for your cells: this biological delivery service could treat disease

From Nature News by Alison Abbott

Researchers want to know why cells produce tiny packages called vesicles — and whether these bundles could be used for therapy.

Graça Raposo was a young postdoc in the Netherlands in 1996 when she discovered that cells in her laboratory were sending secret messages to each other.

She was exploring how immune cells react to foreign molecules. Using electron microscopy, she saw how cells ingested these molecules, which became stuck to the surface of tiny intracellular vesicles. The cells then spat out the vesicles, along with the foreign cargo, and Raposo captured them.

Next, she presented them to another type of immune cell. It reacted to the package just as it would to a foreign molecule.

It was a demonstration that these extracellular vesicles (EVs, also known as exosomes) might be transmitting information between cells.

“We knew that exosomes existed, but at that time they were generally thought to be a way of getting rid of a cell’s trash,” says Raposo. “It was exciting to find that some could have important biological functions — even if not everyone believed it at first.”

Just two years later, together with her colleagues, Raposo, who is now at the Curie Institute in Paris, found that exosomes derived from antitumour immune cells could be enlisted to suppress cancers in mice.

Other scientists jumped on the concept, and began to find exosomes being spat out from all kinds of cell. Interest exploded after researchers discovered that the little packages could contain not only proteins, but also nucleic acids. In 2007, for instance, a Swedish team found that the vesicles harboured small RNA molecules. That implied that exosomes might influence gene expression when they reached their destination cells. The number of EV-related publications rose steeply, and has tripled in the past five years.

As the field has matured, researchers have set out more-stringent rules for what counts as an EV and have established guidelines for how to identify these minuscule bubbles in living systems. Scientists are learning ever more about how vesicles move in and out of cells and across the complex terrain between them, as well as about the roles of vesicles in health and disease. EVs might, for example, be responsible for cancers spreading in the body, or could even be involved in the ageing process.

It is all very much a work in progress, but there is a strong sense of promise in the field. Researchers hope that EVs could be exploited to diagnose, or even treat, various diseases. The number of patent applications and registered clinical trials has soared in parallel with the rise in publications.

But there is also a dark side. To the concern of regulatory agencies, hundreds of private clinics and companies selling unproven EV-based therapies have sprung up around the world, offering to treat anything from Alzheimer’s disease to baldness.

“The number of direct-to-consumer companies peddling EV treatments without proof of safety or efficacy is shocking,” says stem-cell biologist Darius Widera at the University of Reading, UK.


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