Interferon-beta (IFN-??), a well-established standard treatment for multiple sclerosis (MS), has proved to exhibit clinical efficacy.\r\nIn this study, we first evaluated the therapeutic effects for MS using human bone marrow-derived mesenchymal stem cells (hBMMSCs)\r\nas delivery vehicles with lesion-targeting capability and IFN-?? as therapeutic gene.We also engineered hBM-MSCs to secret\r\nIFN-?? (MSCs-IFN??) via adenoviral transduction and confirmed the secretory capacity of MSCs-IFN?? by an ELISA assay. MSCs-\r\nIFN??-treated mice showed inhibition of experimental autoimmune encephalomyelitis (EAE) onset, and the maximum and average\r\nscore for all animals in each group was significantly lower in the MSCs-IFN??-treated EAE mice when compared with the MSCs-\r\nGFP-treated EAE mice. Inflammatory infiltration and demyelination in the lumbar spinal cord also significantly decreased in the\r\nMSCs-IFN??-treated EAE mice compared to PBS- or MSCs-GFP-treated EAE mice. Moreover, MSCs-IFN?? treatment enhanced\r\nthe immunomodulatory effects, which suppressed proinflammatory cytokines (IFN-?? and TNF-??) and conversely increased antiinflammatory\r\ncytokines (IL-4 and IL-10). Importantly, injected MSCs-IFN?? migrated into inflamed CNS and significantly reduced\r\nfurther injury of blood-brain barrier (BBB) permeability in EAE mice.Thus, our results provide the rationale for designing novel\r\nexperimental protocols to enhance the therapeutic effects for MS using hBM-MSCs as an effective gene vehicle to deliver the\r\ntherapeutic cytokines.
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