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regeneration is associated with the secretion of trophic factors like NGF, FGF-2,
BDNF, or NT-3 by Schwann cells [ 371 ]. Schwann cells remain biologically active
in the CNS for long periods of time, and have been shown to survive, integrate, and
support axonal growth up to 5 weeks after transplantation in rat contusion SCI mod-
els [ 370 ]. In addition, more recent studies have reported cell survival for up to 6
weeks after transplantation in multichannel scaffolds [ 372 ]. Nonetheless, Schwann
cells also exhibit limited migration from the graft site as a result of their inability to
coexist with or migrate beyond astrocytes, resulting in axonal stalls at the graft-host
interface [ 373 ]. As such, it is unlikely that Schwann cells alone will be suffi cient to
stimulate neuroregenerative effects in the CNS, but may play integral roles in com-
binatorial approaches to repair damage in the brain or spinal cord.
7.7.4 Mesenchymal Stem Cells
MSCs are adult stem cells obtained from bone marrow, blood, adipose, and dental
tissues. MSCs are quickly and easily expanded in vitro, are easily isolated, can
maintain their viability after cryopreservation at −80 °C, are able to self-renew, and
have been reported to differentiate into essentially all non-hematopoietic lineages
such as osteoblasts, adipocytes, chondrocytes, myoblasts, and early progenitors of
neural cells [ 374 , 375 ]. In fact, MSCs have been demonstrated to adopt neuronal
phenotypes in in vitro studies and after in vivo transplantation in contusion SCI,
stroke, TBI, and neurodegenerative disease models [ 376 – 380 ]. As a transplant
option for neuroregeneration, MSCs are particularly useful due to a lack of antigens
that trigger detrimental graft-versus-host responses [ 381 ]. Further, MSCs them-
selves secrete a number of anti-infl ammatory, anti-apoptotic, and trophic signaling
factors that support axonal growth, remyelination, and protection from cellular
apoptosis [ 380 , 382 ]. These many positive characteristics make MSCs unique can-
didates for autologous transplantation in the CNS in place of tumorigenic, ethically
questionable ESCs [ 326 ]. Furthermore, MSC treatment in the mouse brain was
associated with enhanced survival outcomes after observed increases in prolifera-
tion of endogenous neurons and oligodendrocytes after CCI and induced ischemia,
results of which were correlated with the expression of BDNF, FGF, Bcl2, and NGF
by MSCs [ 383 – 385 ].
Although, these neurotrophic and anti-infl ammatory effects have primarily beenobserved in the brain, a recent study of MSC grafts after spinal cord compression
injury found that MSC transplants secrete NGF and promote signifi cant tissue spar-
ing within the lesion area [ 386 ]. Further, results showed that grafted rats exhibit
signifi cantly greater revascularization than non-grafted rats [ 386 , 387 ]. Taken
together, these data illustrate a role for MSC transplants in promoting endogenous
repair of host tissue. MSC transplants may also serve as a means of molecular deliv-
ery as several research groups have genetically engineered MSCs to deliver neuro-
trophic factors, receptor kinases, and HGF in an effort to promote graft survival and
regeneration of host tissue [ 325 , 386 ].
A. Roussas et al.