Long-term fate of human telencephalic progenitor cells grafted into the adult mouse brain: effects of previous amplification in vitro.
We assessed the developmental potential of human telencephalic progenitor cells, with and without previous amplification in vitro, following grafting into the nonlesioned adult mouse CNS. Cell suspensions, shown to contain neuroepithelium-like and neuroblast-like cells, were injected into the subventricular zone (SVZ) and the striatum. These two regions were selected for comparative studies because one, the SVZ, is mitotically active, whereas the other, the striatum, is mitotically inactive. In situ hybridization with a human-specific Alu probe showed that the cells survived for up to 30 weeks in both targets and migrated away from the injection site. Fresh cells continued to proliferate and gave rise to very extended grafts before differentiating into neurons and glia. We further show that, when grown in vitro prior to grafting, human cells acquired new properties: Their proliferation was very limited, and they differentiated more rapidly. This study therefore provides new information about the use of these cells, which are a potential tool for both cellular and gene therapy.
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 7091, Bâtiment CERVI, Hôpital de la Pitié Salpêtrière, Paris, France.
Delphine
D
Buchet
Marie-Hélène
MH
Buc-Caron
Olivier
O
Sabaté
François
F
Lachapelle
Jacques
J
Mallet
D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000196:embryology / Q000601:surgery; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D017072:Neostriatum / Q000166:cytology / Q000196:embryology* / Q000601:surgery; D009419:Nerve Tissue Proteins; D064231:Nestin; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D013687:Telencephalon / Q000166:cytology / Q000196:embryology* / Q000637:transplantation*; D014404:Tubulin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016900:Neurofilament Proteins; D018809:Proliferating Cell Nuclear Antigen; D014404:Tubulin; D014746:Vimentin; C085284:microtubule-associated protein 1B; D016875:tau Proteins; D016222:Fibroblast Growth Factor 2; D001973:Bromodeoxyuridine