152
only with pMNs decreased apoptosis and neuronal differentiation while simultane-
ously promoting axonal elongation and transplant integration into the host tissue
[ 412 ]. While these studies do show promise for the effectiveness of combinatorial
methods using only biomaterials, trophic factors, and a single cell type, more work
is necessary to fi ne-tune the sensitive interactions between carrier, signaling factors,
and cells.
Other groups have provided evidence that multiple neural cell types and
neurotrophic factors transplanted in biomaterial scaffolds may support cellular
transplantation. For example, co-transplantation of NPSCs and Schwann cells in
electrospun PLGA scaffolds has been shown to enhance axonal regeneration in sev-
eral studies [ 413 – 415 ]. Xia et al. demonstrated that NPSCs and Schwann cells in
PLGA scaffolds promote axonal elongation in vivo; however, there was no differen-
tiation of NPSCs into neuronal phenotypes in groups transplanted with Schwann
cells, and axons were not able to form synaptic connections. Xiong et al. expanded
on this approach by co-seeding NPSCs and Schwann cells in NT-3 loaded PLGA
scaffolds in vitro [ 413 ]. The authors reported increased differentiation of NPSCSs
into neurons and enhanced formation of active synaptic connections and myelina-
tion of neurites by the accompanied Schwann cells in vitro [ 413 ]. Taken together,
this information suggests that while combinatorial techniques may indeed be capa-
ble of addressing current therapeutic limitations, there is still work to be done in
determining the most effective therapeutic combinations.
References
- Langlois JA, Rutland-Brown W, Thomas KE (2006) Traumatic brain injury in the United
States: emergency department visits, hospitalizations, and deaths. Department of Health and
Human Services, Centers for Disease Control and Prevention, Division of Acute Care,
Rehabilitation Research and Disability Prevention, National Center for Injury Prevention and
Control - Yarnall A, Archibald N, Burn D (2012) Parkinson’s disease. Medicine (Baltimore) 40:529–
535. doi: 10.1016/j.mpmed.2012.07.008 - Mergenthaler P, Dirnagl U, Meisel A (2004) Pathophysiology of stroke: lessons from animal
models. Metab Brain Dis 19:151–167. doi: 10.1023/B:MEBR.0000043966.46964.e6 - Hagen EM, Lie SA, Rekand T et al (2010) Mortality after traumatic spinal cord injury: 50
years of follow-up. J Neurol Neurosurg Psychiatry 81:368–373 - Tator CH (1998) Biology of neurological recovery and functional restoration after spinal cord
injury. Neurosurgery 42:696–707 - The National Spinal Cord Injury Statistical Center (2015) Spinal cord injury (SCI) facts and
fi gures at a glance. Retrieved from: https://www.nscisc.uab.edu/Public/Facts%202015%20
Aug.pdf - Ma VY, Chan L, Carruthers KJ (2014) Incidence, prevalence, costs, and impact on disability
of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury,
traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and
back pa. Arch Phys Med Rehabil 95:986.e1–995.e1. doi: 10.1016/j.apmr.2013.10.032 - Blesch A, Lu P, Tuszynski MH (2002) Neurotrophic factors, gene therapy, and neural stem
cells for spinal cord repair. Brain Res Bull 57:833–838. doi: 10.1016/S0361-9230(01)00774-2
A. Roussas et al.