Increased efficacy of adipose-derived mesenchymal stem cells transduced with klotho in differentiation and maturation of oligodendrocytes in a mouse model of experimental autoimmune encephalomyelitis.

Abstract

Current therapies for multiple sclerosis (MS) exert immunomodulatory effects but do not directly repair central nervous system (CNS) damage. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy for MS, as they have been shown to promote myelin repair. Genetic modifications of MSCs have been reported to enhance their therapeutic efficiency in neurodegenerative diseases. This study aimed to investigate the therapeutic potential of MSCs engineered with secreted klotho (s-KL) in enhancing remyelination by mature oligodendrocytes in an experimental autoimmune encephalomyelitis (EAE) model in mice. The results showed that MSCs carrying s-KL alleviated clinical signs and reduced inflammation and demyelination in the CNS more significantly than MSCs. Compared to MSCs, s-KL MSCs also exhibited an enhanced capacity for differentiation and maturation of oligodendrocytes, as demonstrated by increased mRNA and protein expression of Olig2 and Nogo-A in the CNS of mice with EAE. These findings indicate that overexpression of s-KL enhances the therapeutic potential of MSCs to induce remyelination and may represent a novel approach to improve the efficacy of stem cell-based therapy in MS.