Gene Therapy of Multiple Sclerosis Using Interferon beta-Secreting HumanBone Marrow Mesenchymal Stem Cells

Collection with item attached
2013
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/479388.do
DOI
10.1155/2013/696738
Title
Gene Therapy of Multiple Sclerosis Using Interferon beta-Secreting HumanBone Marrow Mesenchymal Stem Cells
Description
This study was supported by a Grant of the Korea Health Technology R&DProject, Ministry of Health & Welfare, Republic of Korea (A092258 andA110330). The authors thank Genexine Co., Ltd., for providing them withAd-IFN-beta.
abstract
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.
provenance
Made available in Cube on 2018-09-28T12:58:14Z (GMT). No. of bitstreams: 0
language
English
author
Ryu, Chung Heon
Park, Kwang Ywel
Hou, Yun
Jeong, Chang Hyun
Kim, Seong Muk
Jeun, Sin-Soo
accessioned
2018-09-28T12:58:14Z
available
2018-09-28T12:58:14Z
issued
2013
citation
BIOMED RESEARCH INTERNATIONAL
issn
2314-6133
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/479388.do
Funder
보건복지부
Funding Program
보건의료기술연구개발
Project ID
1465010210
Jurisdiction
Rep.of Korea
Project Name
Combination therapy for glioma using valproic acid and HSV-TK expressing MSCs
rights
openAccess
type
article


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