Genetically perpetuated human neural stem cells engraft and differentiate into the adult mammalian brain

Citation
Fj. Rubio et al., Genetically perpetuated human neural stem cells engraft and differentiate into the adult mammalian brain, MOL CELL NE, 16(1), 2000, pp. 1-13
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR AND CELLULAR NEUROSCIENCE
ISSN journal
1044-7431 → ACNP
Volume
16
Issue
1
Year of publication
2000
Pages
1 - 13
Database
ISI
SICI code
1044-7431(200007)16:1<1:GPHNSC>2.0.ZU;2-Y
Abstract
Human neural stem cells (HNSCs) may serve as a cellular vehicle for molecul ar therapies as well as for cell replacement in the human CNS. The survival , integration, and differentiation of HNSC.100, a multipotent cell line of HNSCs (A. Villa et al. (2000), Exp. Neurol. 161, 67-84), conditionally perp etuated by genetic and epigenetic means, was investigated after transplanta tion to the striatum and substantia nigra of the adult, intact rat brain. T hese are two key regions in the mammalian brain involved in the control of voluntary movement and motor coordination, among other functions. Soon afte r transplantation (1 week), the cells had already integrated in a nondisrup tive manner into the surrounding tissue and migrated out of the implantatio n site to different distances depending on graft location (in the range of 0.5-2.5 mm). Cell migration was markedly more extensive in the striatum, wh ere the cells colonized the whole extent of the caudate-putamen, than in th e substantia nigra region. The engrafted cells completely downregulated the stem cell marker nestin and, due to their multipotential nature, different iated and expressed mature neural markers. As expected from cells grafted i nto nonneurogenic regions of the intact brain, the majority of differentiat ed cells expressed GFAP (astroglia), but expression of other markers, like GalC (oligodendroglia) and MAP2, beta-tubulin III, NeuN, and NSE (for matur e neurons) could also be detected. These results demonstrate that genetical ly perpetuated HNSCs, once transplanted, find residence in the host brain, where they differentiate, generating mature neural cells in the host, chime ric, adult mammalian brain. HNSCs cell lines may be a highly useful model f or the development of humanized systems for cell replacement and/or gene tr ansfer to the CNS, which will likely be strong candidates for future therap eutic application in human neurodegenerative conditions.