Amniotic Fluid Stem Cell derived Esovesicles modulate pathogenic immune responses in experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a complex disease of immune dysfunction and neurodegeneration and shows a female preponderance, although late pregnancy is the one condition that most profoundly mitigates MS symptoms. Serum exosomes, released by specific cell types during pregnancy, modulate the immune and central nervous systems and contribute to pregnancy-associated suppression of experimental autoimmune encephalomyelitis (EAE), an induced model of MS. The aim of our study was to control the inflammatory response and immune dysfunction in EAE, by administration of exovesicles (EVs) derived from Human Amniotic Fluid-derived Stem Cells (HASCs). We found that vesicles from HASCs were able to prevent autoimmune responses in EAE, suppressing inflammatory cytokines and promoting immunoregulatory effects. Moreover, we found that treatment with EVs, significantly reduced disease severity in EAE, relative to controls. Specifically, treatment with EVs reduced neurological deficits and suppressed Rorc, IL-17 and IL-4 in brain lymphnodes (BLN), while increased the percentage of regulatory T (Treg-Foxp3+) cells. In addition, treatment with EVs during EAE, promoteed a significant increase of the immune regulatory indoleamine 2,3-dioxygenase 1 (IDO1) mRNA. Taken together, the immunomodulatory effects observed from exosomes warrant further exploration into the active components mediating the proposed paracrine effects. The initial evidence strongly suggests that HASC-derived exosomes are the active therapeutic entities, and in this regard our study serves as an opportunity to develop biological therapeutic that harnesses the immunomodulatory and protective properties of stem cells.