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treatment of stroke by reducing infarct size and promoting recovery of motor processes
[ 395 ]. However, the mechanisms behind ADSC- mediated post-injury enhancement of
motor function have yet to be fully elucidated in injury models of the brain.
In the spinal cord, there is evidence to suggest that partial recovery of motor func-tion after SCI may be due to the stimulation of angiogenesis and neurogenesis by
ADSCs [ 399 , 402 ]. An in vitro study of ADSCs transplanted into simulated hypoxic
conditions revealed enhanced neovascular formations, axonal growth, which corre-
lated with signifi cant functional recovery after in vivo transplantation into a rat SCI
model [ 399 ]. These results were likely due to secretion of VEGF by ADSCs, as
NPSCs co-transplanted with ADSCs exhibited signifi cantly reduced apoptosis in the
presence of ADSCs , while treatment with anti-VEGF attenuated this effect in a dose-
dependent manner [ 399 ]. Zhou et al. corroborated these fi ndings in rats that under-
went bilateral dorsal laminectomy [ 402 ]. Human ADSCs (hADSCs) themselves
exhibited elevated expression of VEGF and BDNF as compared to transplanted
human bone marrow stem cells (hBMSCs) [ 402 ]. This expression was correlated
with marked increases in angiogenesis and axon preservation and decreases in local
activation of macrophages/astrocytes and lesion cavity formation in hADSC treated
rats as compared to hBMSC rats [ 402 ]. Further, ADSC- derived Schwann cells have
been shown to express a wide range of neurotrophic factors including NGF, BDNF,
GDNF, and neurotrophin-4 (NT-4) [ 403 ]. Zainy et al. observed ADSC-derived
Schwann cells modulate the hostile environment in a full transection SCI model to
support axon regeneration and enhance functional recovery via the secretion of these
molecules [ 404 ]. Finally, there are successful phase 1 and phase 2 clinical trials
demonstrating the safety of autologous ADSC transplantation in acute spinal cord
injury to improve functional outcome of treated patients [ 405 ].
7.8 Combinatorial Techniques to Enhance
Neuroregeneration
Although there are many promising techniques to promote neural and endogenous
regeneration after central nervous system injury, no specifi c technique has proved to
be all encompassing in treating the number of factors impeding neuroregeneration
in the CNS. As such, it is thought that a multifactorial approach , utilizing the desir-
able attributes of all the current methodologies and applying them in a simultaneous
treatment, may be benefi cial. As discussed, biomaterials can serve as excellent
delivery vehicles for drugs, bioactive factors, and cells while providing physical
support for grafted cells to ensure retention and distribution at the transplantation
site. Matrices like these may enhance cell survival post-transplantation and promote
differentiation into desired phenotypes based on the scaffolds properties. As such,
many groups have attempted to incorporate combinations of neurotrophic signaling,
drug delivery, cellular delivery, and hydrogel scaffolding in one treatment approach
with varying results. Our review found that while modest attempts have been
A. Roussas et al.