Abstract
The ability to promote regeneration of the central nervous system remains elusive. Stroke is a leading cause of
death and disability and creates immense burdens on stroke survivors, their caregivers, and society. Although
acute stroke care has rapidly progressed over the past decades, only a small proportion of the patients qualify
for these treatments. This leaves a majority of stroke patients without effective medical therapy to augment their
stroke recovery. Biomaterials offer a unique avenue to interact with the nervous system. Stem cell treatments
are another emerging stroke therapy that shows promise in both basic and clinical trials. However, the optimal
method and environment for stem cell delivery remains unknown. We have developed a new stem cell delivery
system (ElectricStem) that utilizes conductive polymer scaffolds to transplant neural stem cells into the stroked-
brain. Because the polymers are conductive, electrical stimulation can be combined with the transplanted neural
stem cells. We have demonstrated that electrical modulation of transplanted neural stem cells dramatically
improves stroke recovery over traditional stem cell transplantation alone. In our preliminary studies, electrical
modulation of neural stem cell transplants also increases the production of endogenous stem cells in the brain
– suggesting a possible mechanism for this improved recovery. Further investigation about the role these
endogenous stem cells play in stroke recovery will identify important stroke recovery mechanisms. By evaluating
what proteins are upregulated in the transplanted neural stem cells that receive electrical modulation, we have
identified stanniocalcin-2 (STC2) as an important pathway for improved recovery. STC2 is a glycoprotein with
paracrine effects that plays a role in cell turnover and survival. If STC2 production is increased in transplanted
neural stem cells, the animals have improved functional outcomes, and we see greater numbers of endogenous
stem cells produced. If STC2 levels are decreased in the stem cells, the improvement in function and
endogenous stem cell production is lost. Our proposed research investigates the ability of ElectricStem to recruit
endogenous stem cells and alter their activity within the injured rodent brain tissue following stroke. The effects
of electrical modulation on the transplanted neural stem cells and host brain will be evaluated in relation to the
STC2 pathway. The project will also evaluate if STC2 is a potential therapy for stroke recovery. Finally, our
ElectricStem system will be used in a translational aged rodent model to determine if the promising functional
improvements seen in young adult animals are observed in older animals. Using these new techniques, we aim
to test the hypothesis that augmentation of important endogenous recovery pathways via bioengineered systems
will improve neural repair following stroke.
