The study was financed by the Swedish Foundation for Strategic Research and the Research Council. "Our findings are an important step in the right direction and demonstrate that EVs can be a promising treatment for inflammation, but the technique also has great potential for many other diseases," says Samir EL Andaloussi, principal investigator at the Department of Laboratory Medicine, Karolinska Institutet and joint last author of the study with Joel Nordin from the same department. Treatment with EVs expressing both receptors also showed a significant increase in survival in mouse models for IBD. In the MS model, the researchers also found a significant reduction in the neurological symptoms seen in MS flare-ups. In the animal model for sepsis, treatment significantly improved survival, suggesting a successful dampening of the inflammatory response. The researchers then examined the effects of therapeutic EVs in three relevant inflammatory animal models for sepsis (blood poisoning), MS and IBD. "We used different methods to optimise the expression of receptors and tested the different variants of EVs in inflammatory cell models to identify which strategy gave the greatest anti-inflammatory effect," says Dhanu Gupta, doctoral student at the Department of Laboratory Medicine, Karolinska Institutet, joint first author of the study with departmental colleague Oscar Wiklander. In the present study, the researchers tried to inhibit the inflammatory substances using therapeutic EVs that express on their membranes the receptors that bind to IL 6 and TNF-α. This knowledge has resulted in the development of biological drugs that dampen the inflammatory response by inhibiting TNF-α and IL 6. TNF-α and IL 6 form in the body under inflammatory conditions such as multiple sclerosis (MS) and inflammatory bowel disease (IBD), and play a key part in inflammation and the subsequent tissue damage. Using biomolecular techniques, researchers at Karolinska Institutet have coated the outer EV membrane with therapeutic proteins, more precisely receptors that bind to the inflammatory substances TNF-α and interleukin 6 (IL 6). Consequently, EVs have garnered growing interest as potential drugs.
The tiny bubbles are found naturally in bodily fluids, are able to pass through biological barriers, like the blood-brain barrier, and can be used as natural carriers of therapeutic substances. They are nanometre-sized membrane-coated packages excreted by cells that can deliver fatty acids, proteins and genetic material to different tissues. Extracellular vesicles (EVs) are important in inter-cellular communication as carriers of biological signals.
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