Site-Specific Migration and Neuronal Differentiation of Human Neural Progenitor Cells after Transplantation in the Adult Rat Brain

TLDR

Human forebrain neural progenitor cells were expanded up to 10^7‑fold in vitro with epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor. When transplanted into adult rat neurogenic regions, the expanded human neural progenitors migrated along endogenous pathways to the olfactory bulb and dentate gyrus, differentiated site‑specifically into neurons, and also dispersed nondirectionally in the striatum up to ~1–1.5 mm, where glial‑like cells migrated further while neuronal cells stayed near the graft, demonstrating their capacity to respond to guidance cues and differentiate along multiple phenotypes for potential therapeutic use.

Abstract

Neural progenitor cells obtained from the embryonic human forebrain were expanded up to 10 7 -fold in culture in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory growth factor. When transplanted into neurogenic regions in the adult rat brain, the subventricular zone, and hippocampus, the in vitro propagated cells migrated specifically along the routes normally taken by the endogenous neuronal precursors: along the rostral migratory stream to the olfactory bulb and within the subgranular zone in the dentate gyrus, and exhibited site-specific neuronal differentiation in the granular and periglomerular layers of the bulb and in the dentate granular cell layer. The cells exhibited substantial migration also within the non-neurogenic region, the striatum, in a seemingly nondirected manner up to ∼1–1.5 mm from the graft core, and showed differentiation into both neuronal and glial phenotypes. Only cells with glial-like features migrated over longer distances within the mature striatum, whereas the cells expressing neuronal phenotypes remained close to the implantation site. The ability of the human neural progenitors to respond in vivo to guidance cues and signals that can direct their differentiation along multiple phenotypic pathways suggests that they can provide a powerful and virtually unlimited source of cells for experimental and clinical transplantation.