rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-11-12
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pubmed:abstractText |
The extracellular matrix protein fibronectin is implicated in neuronal regeneration in the peripheral nervous system. In the central nervous system (CNS), fibronectin is up-regulated at sites of penetrating injuries and stroke; however, CNS neurons down-regulate the fibronectin receptor alpha5beta1 integrin during differentiation and generally respond poorly to fibronectin. NT2N CNS neuron-like cells (derived from NT2 precursor cells) have been used in preclinical and clinical studies for treatment of stroke and a variety of CNS injury and disease models. Here we show that, like primary CNS neurons, NT2N cells down-regulate alpha5beta1 integrin during differentiation and respond poorly to fibronectin. The poor neurite outgrowth by NT2N cells on fibronectin can be rescued by transducing NT2 precursors with a retroviral vector expressing alpha5 integrin under the control of the murine stem cell virus 5' long terminal repeat. Sustained alpha5 integrin expression is compatible with the CNS-like neuronal differentiation of NT2N cells and does not prevent robust neurite outgrowth on other integrin ligands. Thus, alpha5 integrin expression in CNS neuronal precursor cells may provide a strategy for enhancing the outgrowth and survival of implanted cells in cell-replacement therapies for CNS injury and disease.
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pubmed:grant |
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pubmed:commentsCorrections |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1097-4547
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
222-32
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pubmed:dateRevised |
2011-7-19
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pubmed:meshHeading |
pubmed-meshheading:19598247-Cell Adhesion,
pubmed-meshheading:19598247-Cell Line,
pubmed-meshheading:19598247-Extracellular Matrix,
pubmed-meshheading:19598247-Fibronectins,
pubmed-meshheading:19598247-Fluorescent Antibody Technique,
pubmed-meshheading:19598247-Gene Expression,
pubmed-meshheading:19598247-Genetic Vectors,
pubmed-meshheading:19598247-Image Processing, Computer-Assisted,
pubmed-meshheading:19598247-Immunoprecipitation,
pubmed-meshheading:19598247-Integrin alpha5,
pubmed-meshheading:19598247-Lentivirus,
pubmed-meshheading:19598247-Neurites,
pubmed-meshheading:19598247-Neurogenesis,
pubmed-meshheading:19598247-Neurons,
pubmed-meshheading:19598247-Transfection
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pubmed:year |
2010
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pubmed:articleTitle |
Expression of alpha5 integrin rescues fibronectin responsiveness in NT2N CNS neuronal cells.
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pubmed:affiliation |
Department of Biology, University of Iowa, Iowa City, Iowa, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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