title: Expression of alpha5 integrin rescues fibronectin responsiveness in NT2N CNS neuronal cells.
abstract: 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.
authors: Department of Biology, University of Iowa, Iowa City, Iowa, USA.
authors: Marit N
authors: MN
authors: Meland
authors: Mary E
authors: ME
authors: Herndon
authors: Christopher S
authors: CS
authors: Stipp
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005822:Genetic Vectors; D007091:Image Processing, Computer-Assisted; D047468:Immunoprecipitation; D039482:Integrin alpha5 / Q000235:genetics* / Q000378:metabolism; D016086:Lentivirus / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection
chemical_list: D005353:Fibronectins; D039482:Integrin alpha5