Gene therapy of multiple sclerosis using interferon β-secreting human bone marrow mesenchymal stem cells

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Abstract

Interferon-beta (IFN-β), a well-established standard treatment for multiple sclerosis (MS), has proved to exhibit clinical efficacy. In this study, we first evaluated the therapeutic effects for MS using human bone marrow-derived mesenchymal stem cells (hBM-MSCs) as delivery vehicles with lesion-targeting capability and IFN-β as therapeutic gene. We also engineered hBM-MSCs to secret IFN-β (MSCs-IFNβ) via adenoviral transduction and confirmed the secretory capacity of MSCs-IFNβ by an ELISA assay. MSCs-IFNβ-treated mice showed inhibition of experimental autoimmune encephalomyelitis (EAE) onset, and the maximum and average score for all animals in each group was significantly lower in the MSCs-IFNβ-treated EAE mice when compared with the MSCs-GFP-treated EAE mice. Inflammatory infiltration and demyelination in the lumbar spinal cord also significantly decreased in the MSCs-IFNβ-treated EAE mice compared to PBS- or MSCs-GFP-treated EAE mice. Moreover, MSCs-IFNβ treatment enhanced the immunomodulatory effects, which suppressed proinflammatory cytokines (IFN-γ and TNF-α) and conversely increased anti-inflammatory cytokines (IL-4 and IL-10). Importantly, injected MSCs-IFNβ migrated into inflamed CNS and significantly reduced further injury of blood-brain barrier (BBB) permeability in EAE mice. Thus, our results provide the rationale for designing novel experimental protocols to enhance the therapeutic effects for MS using hBM-MSCs as an effective gene vehicle to deliver the therapeutic cytokines. © 2013 Chung Heon Ryu et al.

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Ryu, C. H., Park, K. Y., Hou, Y., Jeong, C. H., Kim, S. M., & Jeun, S. S. (2013). Gene therapy of multiple sclerosis using interferon β-secreting human bone marrow mesenchymal stem cells. BioMed Research International, 2013. https://doi.org/10.1155/2013/696738

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