Exosome RNA Exosome RNA Research & Industry News
In an intriguing perspective published in the Journal of Extracellular Vesicles, Dr. Philip Askenase from Yale School of Medicine proposes a new way to understand how extracellular vesicles (EVs) work in the body—by acting in two stages. This idea could help explain some of the most puzzling effects of EV-based therapies, like how they manage to bypass tissue compatibility issues or seem to work in very different disease settings.
The central concept is that EVs—tiny packages released by cells—don’t always act directly on the cells that need healing. Instead, they often first interact with “target” cells, such as macrophages (immune cells that help clean up and coordinate responses in the body). These target cells then produce their own new set of EVs, known as secondary EVs, which actually carry out the final therapeutic effects.
Circuits of primary administered EVs that activate new secondary EVs in the recipients
Two examples illustrate this theory. In immune tolerance, suppressor T cells release EVs that train nearby macrophages to produce secondary EVs that dampen overactive immune responses. In spinal cord injury, EVs from mesenchymal stromal cells (MSCs) interact with tissue macrophages, prompting them to send out secondary EVs that promote healing of local blood vessels and nerves.
This two-step EV process may also explain how MSC-derived EVs work across tissue barriers—something that has puzzled researchers—and why they seem to have specific effects in many different diseases. If the target cells responding to the original EVs produce new EVs tailored to their environment, that might account for the apparent specificity.
Askenase’s hypothesis opens the door to a broader understanding of EV-based therapies. It suggests that the healing power of EVs may often lie not just in what they carry, but in how they instruct other cells to continue the message.
