Oligodendroglia cell-derived extracellular vesicles enriched with HSPB8 reduce neuroinflammation in an MS model

Abstract

Living organisms are constantly exposed to environmental challenges that cause cellular stress, eventually resulting in neuroinflammation. As a response to stress, an increase in the expression of molecular chaperones, called small heat shock proteins (HSPBs), is observed in neuroinflammatory diseases like multiple sclerosis (MS). Unfortunately, administration of excessive HSPBs as a therapeutic strategy triggers a rather short response against MS lesion activity. We reason that the hostile environment found during neuroinflammation incapacitates the HSPBs. Therefore, packaging HSPBs within extracellular vesicles (EVs) could protect them against the inflammatory environment and enable them to execute their protective functions. Almost every cell in our body secretes EVs, which are biological nanocarriers that contain RNAs, proteins, and lipids. Furthermore, their capacity to cross the blood-brain barrier makes them ideal candidates as a drug delivery vehicle for therapeutics to the central nervous system. Our findings demonstrate that OL-EVs and OL-B8-EVs can be internalized by primary co-cultures and cerebellar slices, where they significantly increase autophagy and decrease ROS-mediated cell death. Furthermore, we show that OL-EVs and OL-B8-EVs can upregulate genes involved in the autophagy and ROS pathway. Taken together, our findings provide the next step in the development of cell-specific and next-generation nanotherapeutics capable of modulating neuroinflammatory diseases.