Indexed on: 28 May '13Published on: 28 May '13Published in: BioMed research international
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-IFN β ) via adenoviral transduction and confirmed the secretory capacity of MSCs-IFN β by an ELISA assay. MSCs-IFN β -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-IFN β -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 β -treated EAE mice compared to PBS- or MSCs-GFP-treated EAE mice. Moreover, MSCs-IFN β 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-IFN β 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.