Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain.
The dentate gyrus of the hippocampus is one of the few areas of the adult brain that undergoes neurogenesis. In the present study, cells capable of proliferation and neurogenesis were isolated and cultured from the adult rat hippocampus. In defined medium containing basic fibroblast growth factor (FGF-2), cells can survive, proliferate, and express neuronal and glial markers. Cells have been maintained in culture for 1 year through multiple passages. These cultured adult cells were labeled in vitro with bromodeoxyuridine and adenovirus expressing beta-galactosidase and were transplanted to the adult rat hippocampus. Surviving cells were evident through 3 months postimplantation with no evidence of tumor formation. Within 2 months postgrafting, labeled cells were found in the dentate gyrus, where they differentiated into neurons only in the intact region of the granule cell layer. Our results indicate that FGF-2 responsive progenitors can be isolated from the adult hippocampus and that these cells retain the capacity to generate mature neurons when grafted into the adult rat brain.
Gage
F H
FH
Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Coates
P W
PW
Palmer
T D
TD
Kuhn
H G
HG
Fisher
L J
LJ
Suhonen
J O
JO
Peterson
D A
DA
Suhr
S T
ST
Ray
J
J
D000818:Animals; D015415:Biomarkers; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation; D002470:Cell Survival; D046508:Culture Techniques / Q000379:methods*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology* / Q000601:surgery*; D009474:Neurons / Q000187:drug effects / Q000637:transplantation* / Q000648:ultrastructure; D051381:Rats; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects / Q000648:ultrastructure
D015415:Biomarkers; D016222:Fibroblast Growth Factor 2