1457.7.1 Neural Progenitor/Stem Cells
NPSCs are multipotent, self-renewing precursor cells that give rise to astrocytes,
oligodendrocytes, and neurons in the CNS. In the spinal cord, NPSCs are gener-
ally derived from fetal tissue. However, stem cells derived from fetal tissue
(embryonic stem cells; ESCs ) raise ethical concerns and are prone to tumor
development experimentally [ 326 ]. In light of this, NPSCs have recently been
discovered in the fi lum terminale of adult spinal cord tissue [ 327 – 330 ]. NPSCs
derived from the adult spinal cord consistently produce a neuron to glia ratio of
3:1 [ 331 , 332 ], and thus provide an attractive alternative to ESCs as a cell source
capable of neuronal differentiation. NPSCs transplanted into the spinal cord
after SCI have been reported to persist in the lesion site up to 24 weeks post
injury [ 333 ] and have widely been shown to promote endogenous recovery after
SCI lesion [ 334 – 336 ]. For example, Parr et al. demonstrated increased axon
ensheathing by transplanted NPSCs at the injury site, increased numbers of
endogenous oligodendrocytes , and notable axonal regrowth [ 334 ]. These results
were further corroborated in non-human primate contusion SCI models per-
formed by Nemati et al., who found that SVZ-derived NPSCs transplanted into
the spinal cord of macaque monkeys selectively differentiated into neuronal lin-
eages, homed to the injury site, and promoted improved behavioral outcomes
[ 337 ]. NPSCs also protect against excitotoxicity and secrete neurotrophic fac-
tors such as GDNF, NGF, and BDNF [ 338 , 339 ]. For example, Llado et al.
observed in vitro data suggesting that murine NPSCs implanted adjacent to spi-
nal cord organotypic sections will induce transplant-directed axonal outgrowth
due to secretion of GDNF and NGF by transplanted cells [ 338 ]. Further, spinal
cord explants were protected in the presence of NPSCs against glutamate induced
neurotoxicity [ 339 ]. Similarly, Lu et al. found that NPSCs expressed detectable
levels of GDNF, NGF, and BDNF both in vitro and in vivo, which facilitated host
axonal growth when transplanted in a murine SCI model [ 338 ].
The presence of NPSC transplants in the striatum after brain injury is of particu-lar interest, as it has been associated with enhanced motor and proprioceptive
recovery in neurodegenerative diseases. For instance, both the Anderson and the
Ebert groups employed amphetamine-induced rotation tasks to demonstrate that
NPSC transplantation is associated with increased recovery of motor symmetry
[ 340 , 341 ]. Further, Shear et al. demonstrated that the presence of exogenous
NPSCs in the injured hippocampus persisted up to 12 months post injury in a
rodent model of CCI, which was associated with long-term motor and cognitive
recovery compared to vehicle treatment and non-treatment groups [ 342 ]. Other
experimental TBI studies have demonstrated that transplanted NPSCs decrease
astroglial activation and activated microglial accumulation post-injury in a model
of mechanical hippocampal injury [ 343 ]. Finally, no signifi cant differences in effi -
cacy (as determined by histological analysis) have been observed between adult
and embryonic NPSCs, prompting the necessity for more investigation into trans-
lational applications [ 321 , 344 ].
7 Regenerative Strategies for the Central Nervous System