Fibroblast growth factor-2 overexpression in transplanted neural progenitors promotes perivascular cluster formation with a neurogenic potential.
Stem/progenitor cell-based therapies hold promises for repairing the damaged nervous system. However, the efficiency of these approaches for neuronal replacement remains very limited. A major challenge is to develop pretransplant cell manipulations that may promote the survival, engraftment, and differentiation of transplanted cells. Here, we investigated whether overexpression of fibroblast growth factor-2 (FGF-2) in grafted neural progenitors could improve their integration in the host tissue. We show that FGF-2-transduced progenitors grafted in the early postnatal rat cortex have the distinct tendency to associate with the vasculature and establish multiple proliferative clusters in the perivascular environment. The contact with vessels appears to be critical for maintaining progenitor cells in an undifferentiated and proliferative phenotype in the intact cortex. Strikingly, perivascular clusters of FGF-2 expressing cells seem to supply immature neurons in an ischemic environment. Our data provide evidence that engineering neural progenitors to overexpress FGF-2 may be a suitable strategy to improve the integration of grafted neural progenitor cells with the host vasculature thereby generating neurovascular clusters with a neurogenic potential for brain repair.
Jenny
Benoit
B
Department of Neurosciences, University Medical Center, University of Geneva Medical School, Geneva, Switzerland.
Kanemitsu
Michiko
M
Tsupykov
Oleg
O
Potter
Gael
G
Salmon
Patrick
P
Zgraggen
Eloisa
E
Gascon
Eduardo
E
Skibo
Galina
G
Dayer
Alexandre G
AG
Kiss
Jozsef Z
JZ
D000818:Animals; D001808:Blood Vessels; D002454:Cell Differentiation / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D020925:Hypoxia-Ischemia, Brain / Q000601:surgery*; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D016222:Fibroblast Growth Factor 2