ENGRAFTABLE HUMAN NEURAL STEM-CELLS RESPOND TO DEVELOPMENTAL CUES, REPLACE NEURONS, AND EXPRESS FOREIGN GENES

Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro, Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiat ion into multiple developmentally and regionally appropriate cell type s, and nondisruptive interspersion with host progenitors and their pro geny. These human NSCs can be genetically engineered and are capable o f expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical ge netic metabolic defect in neurons and glia in vitro, The human NSCs ca n also replace specific deficient neuronal populations, Cryopreservabl e human NSCs may be propagated by both epigenetic and genetic means th at are comparably safe and effective, By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a r ange of disorders.