Intranasal delivery of mesenchymal stem cell-derived exosomes ameliorates experimental autoimmune encephalomyelitis

Abstract

Background: Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) have shown therapeutic potential in experimental autoimmune encephalomyelitis (EAE). As a non-invasive method of drug administration, intranasal delivery is anticipated to emerge as a novel option for the treatment of central nervous system (CNS) disorders. Therefore, this study aims to treat EAE by nasal exosomes and explore its specific mechanism, especially its impact on the blood-brain barrier (BBB).

Methods: BMSCs-Exos were isolated and characterized. An EAE model was then established, and these exosomes were administered intranasally to the mice. Changes in body weight and clinical scores were monitored following treatment to assess the efficacy. Additionally, inflammatory infiltrates and demyelination in the CNS were evaluated, alongside the quantification of expression levels of BBB-related adhesion molecules and tight junction (TJ) proteins.

Results: Intranasal delivery of BMSCs-Exos ameliorates the severity of EAE disease, reducing inflammatory infiltration in the CNS and demyelination in the spinal cord. This treatment did not influence the differentiation of T cells in the spleen. Furthermore, the nasal delivery of BMSCs-Exos enhances the integrity of TJs in the cerebral cortex and spinal cord, as well as inhibiting the expression of adhesion molecules. These exosomes promote the expression of TJ-related markers in bEnd3 cells, including ZO-1, Occludin, and Claudin 5. At the same time, they suppress the expression of adhesion molecule-related markers, such as ICAM1 and VCAM1.

Conclusions: Our study suggests that intranasal administration of BMSCs-Exos significantly reduces inflammatory infiltration and demyelination in the CNS of EAE mice. Furthermore, this treatment does not influence the differentiation of T cells in the spleen. Additionally, nasal reinfusion of BMSCs-Exos can improve the integrity of the BBB in EAE mice.

Keywords: Blood-brain barrier; Exosome; Experimental autoimmune encephalomyelitis; Mesenchymal stem cell.