Analysis of recombinant vegf gene expression by genetically modified umbilical cord bloodmononuclear cells in experiment in vivo
Ya O Mukhamedshina , V V Solov'eva , I I Salafutdinov , E E Cherenkova , V Yu Fedotova , Z Z Safiullov , A A Izmaylov , G A Sharifullina , S R Abdulkhakov , M S Kaligin , F V Bashirov , M A Mukhamed'yarov , M M Shmarov , B S Naroditskiy , A P Kiyasov , A A Rizvanov , R R Islamov , Y O Mukhamedshina , V V Solovieva , I I Salafutdinov , E E Cherenkova , V Y Fedotova , Z Z Safiullov , A A Izmailov , G A Sharifullina , S R Abdulhakov , M S Kaligin , F V Bashirov , M A Muhamediarov , M M Shmarov , B S Naroditskii , A P Kiiasov , A A Rizvanov , R R Islamov
Genes & Cells ›› 2012, Vol. 7 ›› Issue (3) : 130 -134.
Analysis of recombinant vegf gene expression by genetically modified umbilical cord bloodmononuclear cells in experiment in vivo
To obtain a significant therapeutic effect transplantedgenetically modified cells should have an enhanced abilityto survive and active expression of the therapeuticgene. In this paper, by using immunofluorescent stainingwe investigated the functional activity of the gene-cellformulation designed to deliver a therapeutic gene into thearea of regeneration. As a model we used transgenic SOD1-G93A mice with amyotrophic lateral sclerosis phenotypewhich received xenotransplantation of human umbilical cordblood mononuclear cells, genetically modified with adenoviralexpression vector encoding vascular endothelial growthfactor (VEGF) and the reporter green fluorescent protein(EGFP).Results of the study allowed to establish not only theduration of survival of transplanted cells, but also theefficiency of expression of recombinant genes in geneticallymodified cells in vivo. Double immunofluorescent stainingwith antibodies against human nuclear antigen HNA andVEGF detected HNA+/VEGF+ cells in the terminal stage ofdisease 15 weeks after transplantation. These data suggestthat genetically modified umbilical cord blood mononuclearcells, transplanted into SOD1-G93A transgenic mice, areable to penetrate the blood-brain barrier and migrate intothe area of degeneration of nerve tissue and survive fromthe time of transplantation until the death of animals at theterminal stage of disease. At that time adenoviral expressionvector encoding therapeutic gene is functionally active intransplanted cells, and secretory products of recombinantgene act on target cells by a paracrine mechanism.
vascular endothelial growth factor / green fluorescent protein / gene-cell therapy / umbilical cord blood mononuclear cells / amyotrophic lateral sclerosis
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