Intranasal administration of conditioned medium derived from mesenchymal stem cells-differentiated oligodendrocytes ameliorates experimental autoimmune encephalomyelitis

Abstract

In multiple sclerosis, myelin sheaths around the axons are degenerated due to uncontrolled inflammation in the central nervous system. Oligodendrocytes (OLs) are myelin-forming cells that secrete trophic factors necessary for myelin protection. Beneficial features of conditioned medium (CM) derived from different stem cells are nowadays under investigation in treating neurodegenerative diseases. Here, we used the differentiation capacity of Wharton's jelly mesenchymal stem cells (WJMSCs) to obtain OLs. Then, the study aimed to evaluate the status of inflammation and myelination in male experimental autoimmune encephalomyelitis (EAE) mice after intranasal administration of CM derived from OLs (OL-CM). Inflammation was studied by evaluating gliosis, inflammatory cell infiltration and expression of inflammation indicators including NLRP3 inflammasome, interleukin-1β, interleukin-18, glial fibrillary acidic protein, and ionized calcium binding adaptor molecule 1. Remyelination was studied by luxol fast blue staining and evaluating the expression of myelin indicators including myelin basic protein and oligodendrocyte transcription factor. In addition, we followed the trend of body weight and functional recovery during the 28-day study. ELISA assay revealed that OL-CM contained brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and ciliary neurotrophic factor. Data showed that OL-CM moderated inflammation, augmented remyelination, and gained normal body weight. Notably, these anti-inflammatory and regenerative effects of OL-CM improved neurological functions in EAE mice. In conclusion, the current study offered a new choice for treating multiple sclerosis using noninvasive intranasal administration of CM harvested from easily achievable WJMSCs-differentiated OLs.