Amyotrophic lateral sclerosis (ALS) is an incurable, chronic, fatal neuro-degenerative disease characterized by
progressive loss of moto-neurons and paralysis of skeletal muscles. Reactivating dysfunctional areas is under earnest investigation
utilizing various approaches. Here we present an innovative gene-cell construct aimed at reviving inert structure
and function. Human umbilical cord blood cells (hUCBCs) transduced with adeno-viral vectors encoding human
VEGF, GDNF and/or NCAM genes were transplanted into transgenic ALS mice models. Significant improvement in behavioral
performance (open-field and grip-strength tests), as well as increased life-span was observed in rodents treated
with NCAM-VEGF or NCAM-GDNF co-transfected cells. Active trans-gene expression was found in the spinal cord of
ALS mice 10 weeks after delivering genetically modified hUCBCs, and cells were detectable even 5 months following
transplantation. Our gene-cell therapy model yielded prominent symptomatic control and prolonged life-time in ALS. Incredible
survivability of xeno-transpanted cells was also observed without any immune-suppression. These results suggest
that engineered hUCBCs may offer effective gene-cell therapy in ALS.
Keywords: Adeno-virus, amyotrophic lateral sclerosis (ALS), gene-cell therapy, glial cell-derived neuro-trophic factor
(GDNF), human umbilical cord blood cell (hUCBC), human umbilical cord blood mono-nuclear cell (hUCB-MC), neural cell
adhesion molecule (NCAM), vascular endothelial growth factor (VEGF), viral vector.
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