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The Journal of Neuroscience, July 15, 1999, 19(14):5990-6005
Site-Specific Migration and Neuronal Differentiation of Human
Neural Progenitor Cells after Transplantation in the Adult Rat
Brain
Rosemary A.
Fricker1, 2,
Melissa K.
Carpenter3, 4,
Christian
Winkler1,
Corinne
Greco3,
Monte A.
Gates1, 2, and
Anders
Björklund1
1 Wallenberg Neuroscience Center, Division of
Neurobiology, Lund University, S-223 Lund, Sweden,
2 Department of Neurology, Harvard Medical School,
Children's Hospital, Boston, Massachusetts 02115, 3 CytoTherapeutics, Lincoln, Rhode Island 02865, and
4 Geron Corporation, Menlo Park, California 94025
Neural progenitor cells obtained from the embryonic human forebrain
were expanded up to 107-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.
Key words:
progenitor cells; human; transplantation; neuron; subventricular zone; dentate gyrus; striatum
Copyright © 1999 Society for Neuroscience 0270-6474/99/19145990-16$05.00/0
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