Hacking communication among cells to turn off inflammation

A study carried out by researchers of Ospedale San Raffaele guided by Roberto Furlan shows that extracellular vesicles may be used to modulate brain inflammation. Researchers employed an experimental model of multiple sclerosis. The study was published in Molecular Therapy and paves the way to the use of vesicles as deliverers of therapeutic molecules.

Cells communicate non-stop with one another using a biochemical language, i.e. exchanging molecules instead of words. One of the ways they talk to their neighbors involves the release of molecules through their membrane into the so-called extracellular vesicles. Researchers have been studying vesicles for a while, with the hope to use them as deliverers of therapeutic messages to cells.

Neurons and glia cellsNeurons and glia cells

Neurons and glia cells (GerryShaw, Wikimedia Commons)

Today in Molecular Therapy a group of researchers of Ospedale San Raffaele – guided by Roberto Furlan, deputy director of the Institute of experimental neurology – show how they managed to engineer specific cells of the central nervous system (microglial cells) so that they could release vesicles that fought inflammation. The vesicles were tested on mice affected by EAE (the experimental model of multiple sclerosis) and caused a reduction of both inflammation and symptoms of the disease. The study was supported by the Italian MS association (AISM) and its foundation (FISM).

Like all cells of our body, central nervous system cells produce extracellular vesicles that carry molecules with a key role for the regulation of several physiological and pathological processes, i.e. synaptic transmission, neurodegeneration and progression of tumors. Patients affected with multiple sclerosis show a particularly intense exchange of vesicles among microglia cells, i.e. immune cells populating the brain and the spinal cord. Researchers noticed a similar phenomenon in animal models.

In this study some cells were engineered in laboratory so that they could produce special extracellular vesicles carrying on their surface an absorption signal (‘eat me’) addressed to microglial cells, which are over-activated in multiple sclerosis. Several molecules were delivered to microglial cells through the vesicles, including IL4, a cytokine that fights inflammation. Once the vesicles were injected into the cerebrospinal fluid – which transported them to the brain and the spinal cord – researchers noticed they reduced inflammation and damage to nervous tissues.

Our study shows that extracellular vesicles might be used as small shuttles to transfer a great variety of molecules, also contemporarily. It is an innovative system to administer drugs and might help us fight several neuroinflammatory diseases” says Roberto Furlan.

Casella G., Colombo F., Finardi A., Descamps H., Ill-Raga G., Spinelli A., Podini P., Bastoni M., Martino G., Muzio L., Furlan R. Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis