期刊
BIOMED RESEARCH INTERNATIONAL
卷 2013, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2013/696738
关键词
-
资金
- Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A092258, A110330]
- Korea Health Promotion Institute [A110330] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Interferon-beta (IFN-beta), 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-beta as therapeutic gene. We also engineered hBM-MSCs to secret IFN-beta (MSCs-IFN beta) via adenoviral transduction and confirmed the secretory capacity of MSCs-IFN beta by an ELISA assay. MSCs-IFN beta-treated mice showed inhibition of experimental autoimmune encephalomyelitis (EAE) onset, and themaximum and average score for all animals in each group was significantly lower in the MSCs-IFN beta-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-IFN beta-treated EAE mice compared to PBS- or MSCs-GFP-treated EAE mice. Moreover, MSCs-IFN beta treatment enhanced the immunomodulatory effects, which suppressed proinflammatory cytokines (IFN-gamma and TNF-alpha) and conversely increased anti-inflammatory cytokines (IL-4 and IL-10). Importantly, injected MSCs-IFN beta 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.
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