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The Journal of Neuroscience, December 1, 2000, 20(23):8727-8735
Adult Spinal Cord Stem Cells Generate Neurons after
Transplantation in the Adult Dentate Gyrus
Lamya S.
Shihabuddin,
Philip J.
Horner,
Jasodhara
Ray, and
Fred
H.
Gage
The Salk Institute, Laboratory of Genetics, La Jolla,
California 92037
The adult rat spinal cord contains cells that can proliferate and
differentiate into astrocytes and oligodendroglia in
situ. Using clonal and subclonal analyses we demonstrate that,
in contrast to progenitors isolated from the adult mouse spinal cord
with a combination of growth factors, progenitors isolated from the adult rat spinal cord using basic fibroblast growth factor alone display stem cell properties as defined by their multipotentiality and
self-renewal. Clonal cultures derived from single founder cells
generate neurons, astrocytes, and oligodendrocytes, confirming the
multipotent nature of the parent cell. Subcloning analysis showed that
after serial passaging, recloning, and expansion, these cells retained
multipotentiality, indicating that they are self-renewing.
Transplantation of an in vitro-expanded clonal population of cells into the adult rat spinal cord resulted in their
differentiation into glial cells only. However, after heterotopic transplantation into the hippocampus, transplanted cells that integrated in the granular cell layer differentiated into cells characteristic of this region, whereas engraftment into other hippocampal regions resulted in the differentiation of cells with astroglial and oligodendroglial phenotypes. The data indicate that
clonally expanded, multipotent adult progenitor cells from a
non-neurogenic region are not lineage-restricted to their developmental origin but can generate region-specific neurons in vivo
when exposed to the appropriate environmental cues.
Key words:
spinal cord; stem cells; FGF; transplantation; neuroplasticity; adult
Copyright © 2000 Society for Neuroscience 0270-6474/00/20238727-09$05.00/0
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