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Title

Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex

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Published in Brain. 2007, vol. 130, no. Pt 11, p. 2962-2976
Abstract Strategies to enhance the capacity of grafted stem/progenitors cells to generate multipotential, proliferative and migrating pools of cells in the postnatal brain could be crucial for structural repair after brain damage. We investigated whether the over-expression of basic fibroblast growth factor 2 (FGF-2) in neural progenitor cells (NPCs) could provide a robust source of migrating NPCs for tissue repair in the rat cerebral cortex. Using live imaging we provide direct evidence that FGF-2 over-expression significantly enhances the migratory capacity of grafted NPCs in complex 3D structures, such as cortical slices. Furthermore, we show that the migratory as well as proliferative properties of FGF-2 over-expressing NPCs are maintained after in vivo transplantation. Importantly, after transplantation into a neonatal ischaemic cortex, FGF-2 over-expressing NPCs efficiently invade the injured cortex and generate an increased pool of immature neurons available for brain repair. Differentiation of progenitor cells into immature neurons was correlated with a gradual down-regulation of the FGF-2 transgene. These results reveal an important role for FGF-2 in regulating NPCs functions when interacting with the host tissue and offer a potential strategy to generate a robust source of migrating and immature progenitors for repairing a neonatal ischaemic cortex.
Keywords AnimalsAnimals, NewbornCell MovementCell ProliferationCerebral Cortex/chemistry/ injuries/pathologyFibroblast Growth Factor 2/analysis/genetics/ metabolismGene ExpressionGenetic EngineeringGenetic Vectors/administration & dosage/geneticsHIV-1/geneticsHumansHypoxia-Ischemia, Brain/surgeryImmunohistochemistryMicroscopy, FluorescenceModels, AnimalRatsRats, Sprague-DawleyStem Cell Transplantation/methodsStem Cells/ metabolism/pathologyTransduction, Genetic/methodsTransgenesWound Healing
Stable URL http://archive-ouverte.unige.ch/unige:10222
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Identifiers
PMID: 17728358
Structures
Research group Progéniteurs neuronaux
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