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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-2
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pubmed:dateCreated |
2008-6-2
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pubmed:abstractText |
Interferon-beta (IFN-beta), an approved treatment of multiple sclerosis (MS), produces only partial clinical responses. IFN-beta therapy has been limited by its short serum half-life and limited ability to cross the blood brain barrier. We have developed a means of delivering the IFN-beta gene both systemically and into the central nervous system (CNS) using bone marrow stem cells (BMSCs) as a vehicle and examined the therapeutic efficacy of this approach in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. A retroviral expression vector (pLXSN-IFNbeta) was used to stably transfect virus producer PA317 cells to generate retrovirus containing the IFN-beta gene which then was used to transduce BMSCs. IFN-beta engineered BMSCs were transplanted (i.v.) into mice that then were immunized with proteolipoprotein (PLP) to initiate EAE. IFN-beta-engineered BMSCs transplanted mice showed a significant inhibition of EAE onset, and the overall clinical severity was less compared to control groups. IFN-beta delivery strongly reduced infiltration of mononuclear cells possibly by inhibiting cell adhesion molecules. Reduced demyelination and increased remyelination were also observed in the IFN-beta treated group. Furthermore, inhibition of the pro-inflammatory cytokines TNF-alpha, IFN-gamma and IL-12 and enhanced expression of the anti-inflammatory cytokines IL-10, IL-4 and TGF-beta was observed in CNS tissue. In addition, mice receiving IFN-beta had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF. These results suggest that BMSCs can be used as vehicles to deliver the IFN-beta into the CNS. This is a potentially novel therapeutic approach which might be used in MS and other diseases of the CNS in which drug access is limited.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Icam1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Myelin Basic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myelin Proteolipid Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/myelin proteolipid protein (139-151)
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0165-5728
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pubmed:author |
pubmed-author:BalasubramanianShaileshS,
pubmed-author:BeverChristopher TCT,
pubmed-author:Dhib-JalbutSuhaylS,
pubmed-author:FordDavidD,
pubmed-author:GoolsbyJames EJE,
pubmed-author:GuptaAditiA,
pubmed-author:MakarTapas KTK,
pubmed-author:PatelNirajN,
pubmed-author:SinghIshwar SIS,
pubmed-author:SultanaShireenS,
pubmed-author:SuraKarna TKT,
pubmed-author:TrislerDavidD,
pubmed-author:ValenzuelaReuben MRM
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
196
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
67-81
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pubmed:dateRevised |
2011-8-26
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pubmed:meshHeading |
pubmed-meshheading:18471898-Animals,
pubmed-meshheading:18471898-Antigens, CD34,
pubmed-meshheading:18471898-Bone Marrow Cells,
pubmed-meshheading:18471898-Bone Marrow Transplantation,
pubmed-meshheading:18471898-Caspase 3,
pubmed-meshheading:18471898-Cells, Cultured,
pubmed-meshheading:18471898-Cytokines,
pubmed-meshheading:18471898-Disease Models, Animal,
pubmed-meshheading:18471898-Encephalomyelitis, Autoimmune, Experimental,
pubmed-meshheading:18471898-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:18471898-Female,
pubmed-meshheading:18471898-Gene Transfer Techniques,
pubmed-meshheading:18471898-In Situ Nick-End Labeling,
pubmed-meshheading:18471898-Intercellular Adhesion Molecule-1,
pubmed-meshheading:18471898-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:18471898-Interferon-beta,
pubmed-meshheading:18471898-Mice,
pubmed-meshheading:18471898-Myelin Basic Proteins,
pubmed-meshheading:18471898-Myelin Proteolipid Protein,
pubmed-meshheading:18471898-Peptide Fragments,
pubmed-meshheading:18471898-Recurrence,
pubmed-meshheading:18471898-Vascular Cell Adhesion Molecule-1
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pubmed:year |
2008
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pubmed:articleTitle |
Stem cell based delivery of IFN-beta reduces relapses in experimental autoimmune encephalomyelitis.
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pubmed:affiliation |
VA Maryland Healthcare System, Baltimore, MD 21201, United States. tmaka001@umaryland.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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