Extracellular vesicles can act as a potent immunomodulators of human microglial cells

Functional impairments of microglia have been recently associated with several neurological conditions. Therefore, modulation of anti-inflammatory and phagocytic properties of microglial cells could represent a novel therapeutic approach. In the present study, we investigated the effects of extracellular vesicles (EVs) derived from stem cells from the dental pulp of human exfoliated deciduous teeth (SHEDs) on the inflammatory response and functional properties of immortalized human microglial cells. NF kappa B reporter assays demonstrated that EVs suppressed LPS-induced activation of NF kappa B signalling pathway in human microglial cells. The effect was similar to that obtained with anti-TLR4 blocking antibody. We also show that EVs differentially affected phagocytic activity of unpolarized (M0) and polarized (M1 and M2) microglial cells. EVs induced significant upregulation of phagocytic activity in M0 cells (by 39%), slight decrease in M1 cells, and moderate increase (by 21%) in M2 cells. The Seahorse XF Glycolysis Stress Test revealed that EVs induced an immediate and sustained increase of glycolytic activity in M0, M1, and M2 cells. Interestingly, EVs acted in an inverse dose-dependent manner. These findings indicate that EVs can induce glycolytic reprogramming of unpolarized and polarized human microglial cells. In conclusion, our pilot study demonstrates that EVs derived from SHEDs can act as a potent immunomodulators of human microglial cells. These findings could be potentially exploited for the development of new therapeutic strategies targeting neuroinflammatory microglia.