Exosomes derived from mesenchymal stem cells attenuate inflammation and demyelination of the central nervous system in EAE rats by regulating the polarization of microglia

Abstract

Multiple sclerosis (MS) is a chronic demyelinating disease caused by central nervous system (CNS) inflammation and immune dysfunction, which often leaves patients with severe physical disabilities. Microglia function in the surveillance of the CNS, and an imbalance in the M1/M2 phenotypes of microglia contribute to the progression of MS. Recent studies indicate that exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) play therapeutic roles in many autoimmune diseases and aid in tissue repair. However, it is not clear whether BMSC-derived exosomes can attenuate MS-associated inflammation and immune dysfunction, or how BMSC exosomes protect neurons. The experimental autoimmune encephalomyelitis (EAE) rat model was used to investigate the effect of exosomes on microglia polarization and inflammation in CNS. The results showed that exosome treatment significantly decreased neural behavioral scores, reduced the infiltration of inflammatory cells into the CNS, and decreased demyelination in comparison to untreated EAE rats. In addition, exosome treatment resulted in significant increases in the levels of M2-related cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β, whereas M1-related tumor necrosis factor (TNF)-α and IL-12 levels decreased significantly. Moreover, compared with the untreated EAE group, the exosome group displayed significantly increased protein and mRNA expression levels of M2 phenotype markers, whereas M1 marker expression decreased. Our findings were further confirmed in an in vitro HAPI microglia cell line model. In conclusion, these findings indicate that BMSC-derived exosomes can attenuate inflammation and demyelination of the CNS in the EAE rat model by regulating the polarization of microglia. Therefore, the use of BMSC-derived exosomes may be a potential therapeutic approach for the treatment of autoimmune and inflammatory diseases.

Keywords: Exosomes; Experimental autoimmune encephalomyelitis; Immunoregulation; Mesenchymal stem cells; Microglia; Polarization.