Analysis of recombinant vegf gene expression by genetically modified umbilical cord bloodmononuclear cells in experiment in vivo
- Authors: Mukhamedshina Y.O1, Solov'eva VV1, Salafutdinov II1, Cherenkova EE1, Fedotova VY.1, Safiullov ZZ1, Izmaylov AA1, Sharifullina GA1, Abdulkhakov SR1, Kaligin MS1, Bashirov FV1, Mukhamed'yarov MA1, Shmarov MM1, Naroditskiy BS1, Kiyasov AP1, Rizvanov AA1, Islamov RR1, Mukhamedshina YO2,3,1, Solovieva VV2,3,1, Salafutdinov II2,3,1, Cherenkova EE2,3,1, Fedotova VY2,3,1, Safiullov ZZ2,3,1, Izmailov AA2,3,1, Sharifullina GA2,3,1, Abdulhakov SR2,3,1, Kaligin MS2,3,1, Bashirov FV2,3,1, Muhamediarov MA2,3,1, Shmarov MM2,3,1, Naroditskii BS2,3,1, Kiiasov AP2,3,1, Rizvanov AA2,3,1, Islamov RR2,3,1
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Affiliations:
- Кazan (Volga region) Federal University, Kazan
- Кazan State Medical University, Kazan
- Issue: Vol 7, No 3 (2012)
- Pages: 130-134
- Section: Articles
- URL: https://genescells.ru/2313-1829/article/view/121636
- DOI: https://doi.org/10.23868/gc121636
- ID: 121636
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Abstract
genetically modified cells should have an enhanced ability
to survive and active expression of the therapeutic
gene. In this paper, by using immunofluorescent staining
we investigated the functional activity of the gene-cell
formulation designed to deliver a therapeutic gene into the
area of regeneration. As a model we used transgenic SOD1-
G93A mice with amyotrophic lateral sclerosis phenotype
which received xenotransplantation of human umbilical cord
blood mononuclear cells, genetically modified with adenoviral
expression vector encoding vascular endothelial growth
factor (VEGF) and the reporter green fluorescent protein
(EGFP).
Results of the study allowed to establish not only the
duration of survival of transplanted cells, but also the
efficiency of expression of recombinant genes in genetically
modified cells in vivo. Double immunofluorescent staining
with antibodies against human nuclear antigen HNA and
VEGF detected HNA+/VEGF+ cells in the terminal stage of
disease 15 weeks after transplantation. These data suggest
that genetically modified umbilical cord blood mononuclear
cells, transplanted into SOD1-G93A transgenic mice, are
able to penetrate the blood-brain barrier and migrate into
the area of degeneration of nerve tissue and survive from
the time of transplantation until the death of animals at the
terminal stage of disease. At that time adenoviral expression
vector encoding therapeutic gene is functionally active in
transplanted cells, and secretory products of recombinant
gene act on target cells by a paracrine mechanism.
About the authors
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
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
V V Solovieva
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
I I Salafutdinov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
E E Cherenkova
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
V Y Fedotova
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
Z Z Safiullov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
A A Izmailov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
G A Sharifullina
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
S R Abdulhakov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
M S Kaligin
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
F V Bashirov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
M A Muhamediarov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
M M Shmarov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
B S Naroditskii
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
A P Kiiasov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
A A Rizvanov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
R R Islamov
Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;Кazan (Volga region) Federal University, Kazan;Кazan State Medical University, Kazan;
References
- Fuss I.J., Kanof M.E., Smith P.D. et al. Isolation of whole mononuclear cells from peripheral blood and cord blood. Curr Protoc Immunol. 2009; Chapter 7: Unit 7.1.
- Завалишин И.А., Бочков Н.П., Суетна З.А. и др. Генная тера- пия бокового амиотрофического склероза. Бюллетень эксперимен- тальной биологии и медицины 2008; 145(4): 467-70.
- Yang W.Z., Zhang Y., Wu F. et al. Safety evaluation of allogeneic umbilical cord blood mononuclear cell therapy for degenerative conditions. J. Transl. Med. 2010; 8:75.
- Ma N., Stamm C., Kaminski A. et al., Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice.Cardiovasc. Res. 2005; 66(1): 45-54.
- Neuhoff S., Moers J., Rieks M. et al. Proliferation, differentiation, and cytokine secretion of human umbilical cord blood-derived mononuclear cells in vitro. Exp. Hematol. 2007; 35(7): 1119-31.
- Vorburger S.A., Hunt K.K. Adenoviral gene therapy. Oncologist 2002; 7(1): 46-59.
- Yan R., Zhang L., Zhang Q. et al. A new finding concerning adenoviral-mediated gene transfer: A high-level, cell-specific transgene expression in the neural stem cells of adult mice. J. Virol. Methods. 2012. Epub ahead of print.
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