149
7.7.5 Olfactory Ensheathing Cells
Olfactory ensheathing cells (OECs) are glial cells found within both the peripheral
and central nervous systems and are signifi cant contributors to the regenerative
capacity of olfactory neurons. In the CNS, OECs are found within the outer layers of
the olfactory bulb, while in the PNS OECs are dispersed within the olfactory epithe-
lium and the olfactory nerve. In either case, OECs form on bundles of olfactory
sensory neuron axons, which are then able to extend and re-enter the olfactory bulb
and re-synapse with second-order neurons in the glomerular layer [ 388 ]. The OECs
interact with resident astrocytes and fi broblasts to facilitate these connections [ 388 ].
Further, OECs are capable of preventing axons from recognizing growth inhibitory
molecules, thereby allowing them to elongate in otherwise inhibitory settings [ 389 ,
390 ]. As such, researchers have used these cells in various SCI models to promote
axonal elongation. In a hemi-transection injury model, injected OECs induced axo-
nal elongation into a denervated caudal host tract [ 391 ]. Similarly, in a transected
adult rat SCI model, OECs signifi cantly enhanced axonal regrowth, allowing axons
to extend through white matter tracts, gray matter, and glial scars [ 390 ]. Other groups
have found that using scaffolding techniques can augment OEC-mediated axonal
growth. In one of the fi rst studies utilizing this method, OECs induced axonal growth
through a Schwann cell-containing channel for distances as long as 2.5 cm and to a
slightly lesser extent in non Schwann cell seeded channels [ 392 ]. Given these prom-
ising results, there are now two successful clinical trials on record using OECs to
promote functional recovery in spinal cord injury patients [ 393 , 394 ].
7.7.6 Adipose-Derived Stem Cells
Adipose-derived stem cells (ADSCs) are more abundant, safer, and can be obtained in
a relatively non-invasive manner compared to other common stem cells [ 395 , 396 ].
Both in vivo and in vitro studies demonstrate that the presence of ADSCs supports
neurogenesis and survival of neural stem cells, illustrating their neuroprotective bene-
fi ts in addition to their safety [ 397 – 399 ]. Further, ADSCs appear to be safe for use in
the spinal cord, as human ADSCs (hADSCs) transplanted into both humans and ani-
mals under various injury models showed no signs of tumorigenicity or adverse effects
3 months post-transplantation [ 396 ]. ADSCs have been recorded to differentiate into
endothelial cells [ 400 ] in vitro after induced hypoxia, support axonal sprouting, and
modify the structure of the glial scar in white matter after full transection [ 401 ].
Because ADSCs are so easily harvested and safe for human use, experiments have
been performed via a number of neurological disorders to assess the therapeutic effi -
cacy of these cells. For instance, research employing a murine model of Alzheimer’s
disease found that transplanted ADSCs both increase neurogenic activity in the SGZ
and SVZ neurogenic niches and decrease the amount of oxidative stress on the neural
environment [ 395 ]. Transplantation of these stem cells has also shown promise in
7 Regenerative Strategies for the Central Nervous System