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Engineered stem cell-derived microglia as therapeutic vehicle for experimental autoimmune encephalomyelitis.
MedLine Citation:
PMID:  23324824     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Inflammation can be prevented in most inflammatory brain diseases, while tissue repair of the lesioned central nervous system (CNS) is still a major challenge. The CNS is difficult to access for protein therapeutics due to the blood-brain barrier. Here, we show that genetically engineered embryonic stem cell-derived microglia (ESdM) are a suitable therapeutic vehicle for neurotrophin-3 (NT3) in experimental autoimmune encephalomyelitis (EAE). The intravenously transplanted ESdM migrated into the inflammatory CNS lesions and engrafted there as microglial cells. EAE afflicted mice treated with ESdM that were genetically modified to express NT3 showed stable recovery from disease symptoms. The NT3-transduced ESdM created an anti-inflammatory cytokine milieu in the spinal cord and promoted neuronal sprouting. Furthermore, mice treated with NT3-transduced ESdM showed less axonal injury and reduced demyelination. Thus, genetically modified ESdM represent a suitable tool to introduce therapeutic neuroprotective and repair-promoting proteins into the CNS in neuroinflammatory diseases.Gene Therapy advance online publication, 17 January 2013; doi:10.1038/gt.2012.100.
Authors:
C Beutner; V Lepperhof; A Dann; B Linnartz-Gerlach; S Litwak; I Napoli; M Prinz; H Neumann
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Gene therapy     Volume:  -     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Neural Regeneration, Institute of Reconstructive Neurobiology, University Bonn and Hertie-Foundation, Bonn, Germany.
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