Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex.
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.
Dayer
Alexandre G
AG
Department of Neurosciences, University Medical Center, University of Geneva Medical School, Geneva, Switzerland.
Jenny
Benoit
B
Sauvain
Marc-Olivier
MO
Potter
Gael
G
Salmon
Patrick
P
Zgraggen
Eloisa
E
Kanemitsu
Michiko
M
Gascon
Eduardo
E
Sizonenko
Stephane
S
Trono
Didier
D
Kiss
Jozsef Z
JZ
D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000737:chemistry / Q000293:injuries* / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000601:surgery; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014161:Transduction, Genetic / Q000379:methods; D019076:Transgenes; D014945:Wound Healing
D016222:Fibroblast Growth Factor 2