Journal Article

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

Alexandre G. Dayer, Benoit Jenny, Marc-Olivier Sauvain, Gael Potter, Patrick Salmon, Eloisa Zgraggen, Michiko Kanemitsu, Eduardo Gascon, Stephane Sizonenko, Didier Trono and Jozsef Z. Kiss

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 11, pages 2962-2976
Published in print November 2007 | ISSN: 0006-8950
Published online August 2007 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awm200
Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex

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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: Brain repair; neonatal ischemia; neural progenitors; transplantation; migration; FGF-2

Journal Article.  7180 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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