Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain

Neural progenitor cells obtained from the embryonic human forebrain were ex panded up to 10(7)-fold in culture in the presence of epidermal growth fact or, basic fibroblast growth factor, and leukemia inhibitory growth factor. When transplanted into neurogenic regions in the adult rat brain, the subve ntricular zone, and hippocampus, the in vitro propagated cells migrated spe cifically along the routes normally taken by the endogenous neuronal precur sors: along the rostral migratory stream to the olfactory bulb and within t he subgranular zone in the dentate gyrus, and exhibited site-specific neuro nal differentiation in the granular and periglomerular layers of the bulb a nd in the dentate granular cell layer. The cells exhibited substantial migr ation also within the non-neurogenic region, the striatum, in a seemingly n ondirected manner up to similar to 1-1.5 mm from the graft core, and showed differentiation into both neuronal and glial phenotypes. Only cells with g lial-like features migrated over longer distances within the mature striatu m, whereas the cells expressing neuronal phenotypes remained close to the i mplantation site. The ability of the human neural progenitors to respond in vivo to guidance cues and signals that can direct their differentiation al ong multiple phenotypic pathways suggests that they can provide a powerful and virtually unlimited source of cells for experimental and clinical trans plantation.