Neural Stem Cell Poster
Neural Stem Cell Poster
Neural Stem Cell Poster
Neuronal
progenitor
Dopamine neurons
Neuroepithelial
cell
Neuroepithelium
Neurons
Radial glia
NSC
Embryonic histogenesis
Adult SVZ
Lateral ventricle
Blastocyst
Reprogramming:
STEMcircles provide a non-viral, non-integrating
approach to reprogramming somatic cells into
iPS cells. STEMcircles vectors have higher
transfection efficiencies and more persistent
expression than regular plasmid-based reprogramming
techniques.
Motor neurons
RA, Shh
BMPs, CNTF,
other factors
Hippocampus
Lateral
ventricle
Glia
Neurospheres
Astrocytes
CNTF, LIF
BMPs
Derivation and
expansion of NSCs
Neural induction:
AggreWell plates allow users to control the size and
shape of embryoid bodies (EBs), allowing reproducibility,
optimization of differentiation protocols to specific
Differentiation
OCT4,
SOX2
Remove
EGF, FGF-2
Hippocampus
Somatic tissue
Add
EGF, FGF-2
Parkinsons disease
FGF-8, Shh
NT-3, NT-4,
low FGF-2
2D monolayer culture
NSCs are located within two regions of the adult human and
rodent brain (green): the subgranular zone of the
hippocampus and the subventricular zone of the striatum2.
Adult NSCs generate new neurons throughout life that
integrate into hippocampal and olfactory circuits and are
thought to be important for memory and olfaction. These
NSCs can be isolated and expanded from rodent brains;
however, they are more difficult to isolate from human brain
biopsies or autopsy samples. Another type of NSC outside
these two regions expresses the marker NG2 and can also
proliferate in vitro and in vivo. However, this cell type does
not normally give rise to new neurons in vivo. NG2 cells can
be activated after injury and can generate new
oligodendrocytes.
BDNF, Dkk1,
Shh, cAMP
Neuroblast
Early embryo
Huntingtons disease
GABA neurons
PMN, VN,
NGN, PDGF,
cAMP, FGF-2
Oligodendrocytes
Transplantation
Expanded naive or partially differentiated populations of NSCs can be transplanted into the
CNS of experimental animals to test their potential to differentiate into functional neuronal
or glial cells in vivo. Such animal studies are the first steps towards developing cell therapies
for neurological disorders. At present, two clinical trials are under way in the USA,
transplanting fetally derived NSCs into the brains of children with Battens disease and
adults with ALS. Such transplants may help by replacing neural tissue and/or by releasing
growth factors that support any remaining functional tissue. One of the major challenges
with NSC-derived transplants is a chance of tumor growth from residual mitogenic cells.
EScell derived transplants in particular may grow teratomas from residual pluripotent,
dividing cells. Fetal- or adult-brain-derived transplants cannot grow teratomas but still carry
some risk of tumorigenicity, which will require careful monitoring. Immune rejection issues
will also be a challenge for this field.
Abbreviations
ALS, amyotrophic lateral sclerosis; BDNF, brain-derived
neurotrophic factor; BMP, bone morphogenetic factor;
cAMP, cyclic adenosine monophosphate; CNS, central
nervous system; CNTF, ciliary neurotrophic factor;
Dkk1, Dickkopf-1; EGF, epidermal growth factor;
ES, embryonic stem (cell); FDA, US Food and Drug
Administration; FGF, fibroblast growth factor;
GABA, g-aminobutyric acid; iPS, induced pluripotent
stem (cell); LIF, leukemia inhibitory factor; NG2, nerve/
glial antigen 2; NGN, neurogenin; NSC, neural stem cell;
NT, neurotrophin; PDGF, platelet-derived growth factor;
References
1. Alvarez-Buylla, A., Garca-Verdugo, J. M. & Tramontin,
A. D. A unified hypothesis on the lineage of neural
stem cells. Nature Rev. Neurosci. 2, 287293 (2001).
2. Zhao, C., Deng, W. & Gage, F. H. Mechanisms and
functional implications of adult neurogenesis. Cell
132, 645660 (2008).
Multiple sclerosis
Oligodendrocyte degeneration leads to
demyelination of axons, which causes slowed
conductance leading to a multitude of
neurological symptoms. In promising animal
studies, transplantation of pre-differentiated
NSCs results in remyelination and renewed
motor function. In human patients, the
challenge is to target transplanted cells to the
many demyelinated lesions that are widely
dispersed throughout the CNS.
Contact information
The authors are affiliated with the Regenerative Medicine
Institute at Cedars-Sinai Medical Center, Los Angeles,
California, USA.
e-mail: [email protected]
Edited by Annette Markus; copyedited by Anita Gould;
designed by Kirsten Lee
2010 Nature Publishing Group
http://www.nature.com/neuro/poster/neuralstemcells/
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