Page 85 - NNS 2014 Program & Abstract Book

early death of transplanted cells. The precise cause of transplanted cell
death remains elusive and strategies that significantly enhance trans-
plant survival have not yet been developed. To date, strategies to
prevent transplanted cell death have focused on either blocking in-
duction of cell death or blocking cell death signaling once started.
Although there has been some success with these strategies, the
presence of multiple cell death inducers and complex cross-talk be-
tween cell death pathways once activated have meant that the effects
of the aforementioned strategies are modest. An alternative strategy is
to counteract acute cell death signaling via direct activation of pro-
survival pathways. One method to elevate prosurvival pathways in
cells is to activate transcription factors involved in endogenous
adaptive responses to stress. Among the transcription factors impli-
cated in adaptive cellular responses to stress are the hypoxia inducible
factors (HIFs). In the current study we examine the effect of en-
hancing HIF activity in Schwann cells transplanted into the injured
spinal cord of rats. We demonstrate that transplanted cells normally
have low levels of HIF transcriptional activity and that enhancing HIF
activity through either overexpression or pharmacological manipula-
tion results in improved survival of transplanted cells. This suggests
that transcription factor activation may be a beneficial strategy for
promoting the survival of transplanted cells.
Key words
cell survival, hypoxia inducible factor, Schwann cells, spinal cord
injury, transcription factor, transplantation
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B2-05
DEVELOPMENT OF A LUMBAR SPINAL CORD INJURY
MODEL TO EXAMINE THE THERAPEUTIC POTENTIAL OF
TRANSPLANTING NEURONALLY INDUCED NSPCS
Moonen, G.1,2, Tator, C.H.1,2
1University of Toronto, Institute of Medical Science, Toronto, Canada
2Toronto Western Hospital, University Health Network, Toronto,
Canada
Patients with injuries to the thoracolumbar region of the spinal
cord often lose clusters of neurons that are essential for loco-
motion. Our focus is on replacing lost neuronal circuitry by
transplanting adult spinal-derived neural stem/progenitor cells
(NSPCs) that have been differentiated into neurons in vitro.
We hypothesize that optimal differentiation of NSPCs in vitro
towards a neuronal lineage will promote transplant survival and
functional recovery after transplantation in the injured lumbar
spinal cord.
NSPCs were treated with 1mM dibutyryl-cyclic AMP (dbcAMP) to
enhance neuronal differentiation and stained with BIII tubulin to
confirm neuronal character. To characterize the lumbar spinal cord
injury model, various modified aneurysm clips (56 g, 35 g, 26 g and
20 g) were applied to 40 adult female Wistar rats (Wi) to assess
spontaneous functional recovery as measured by the open field BBB
locomotor scale. 40 (Wi) rats were injured with a 26 g clip and split
into 4 treatment groups: (1) dbcAMP treated cells + Rolipram injec-
tion (RI) post-op, (2) dbcAMP treated cells + saline injection (SI), (3)
untreated cells + RI, (4) media injection control + SI. Four hundred
thousand cells were transplanted 1mm rostral and caudal to the injury
site in the subacute phase of injury.
DbcAMP robustly differentiated NSPCs towards BIII positive
neurons: 72% – 6.3. Rats recovered spontaneously to 2 – 1 in the most
severe 56 g group, 2.5 – 1 in the 35 g group, 4 – 2.5 in the 26 g group
and 8.5 – 2.5 in the 20 g group after 6 wks. In the transplant study, rats
in the double treatment group (dbcAMP cells + RI) improved to a
statistically significant (p < 0.05) average of 5.16( – 3.2) compared to
dbcAMP + saline = 2.2( – 1.5), untreated cells + RI = 1.1( – 1.07) or
control = 2.2( – 1.3).
We have generated a novel pre-clinical lumbar spinal cord injury
model and displayed that transplant of neuronally differentiated stem
cells results in increased functional recovery.
Key words
CPG, cyclic AMP, lumbar, neural stem cell, neuronal differentiation,
spinal cord
B2-06
DOMAINS OF NEURAL CONTROL OF WALKING IN HU-
MAN SPINAL CORD INJURY
Awai, L.1, Bolliger, M.1, Ferguson, A.R.2, Courtine, G.3, Curt, A.1
1Balgrist University Hospital, Zurich, Switzerland
2University of California San Francisco, San Francisco, USA
3Swiss Federal Institute of Technology, Lausanne, Switzerland
Measures of walking function based on time-distance parameters,
although clinically meaningful for determining ambulatory capacity,
provide limited information on gait quality and changes in neural control
after injury. In incomplete spinal cord injury (iSCI) disentangling dif-
ferent domains of neural control of walking and a stratification of
WITHDRAWN
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