Human umbilical cord blood cells transfected with VEGF and L1CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesis-a novel approach in stem cell therapy

Genetically modified mono-nuclear cell fraction from human umbilical cord blood (HUCB) expressing human Vascular endothelial growth factor (VEGF) and Mouse neural L, cell adhesion molecule (L(1)CAM) were used for gene-stem cell therapy of transgenic (G)93(A) mice adopted as ail animal amyotrophic lateral sclerosis (ALS) model. We generated non-viral plasmid constructs, expressing human VEGF(165), (pcDNA-VEGF) and mouse neural L-1 cell adhesion molecule (pcDNA-mL(1)CAM). Mono-nuclear fraction of HUCB cells were transiently transfected by electro-poration with a mixture of expression plasmids (pcDNA-VEGF + pcDNA-mL(1)CAM). Sixteen transgenic female and male mice were randomly assigned to three groups: (1) transplantation of genetically modified HUCB cells expressing L, and VEGF (n = 6), (2) transplantation of un-transfected HUCB cells (it = 5), and (3) control group (n = 5). In first two experimental groups 1 x 10(6) cells were injected retro-orbitally in pre-symptomatic 22-25-week-old (G)93(A) mice. Our results demonstrate that HUCB cells Successfully grafted into nervous tissue of ALS mice and survived for over 3 months. Therefore, genetically modified HUCB cells migrate in the spinal cord parenchyma, proliferate, but instead of transforming into nerve cells, they differentiate into endothelial cells forming new blood vessels. We propose that: (A) expression Of Mouse neural LICAM is responsible for increased homing and subsequent proliferation of transplanted cells at the site Of neuro-degeneration, (B) expression Of human VEGF directs HUCB cell differentiation into endothelial cells, and (C) neuroprotective effect may stein from the delivery of various neuro-trophic factors from newly formed blood vessels. (C) 2008 Elsevier Ltd. All rights reserved.