Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells

被引：8

作者：

Gatina, Dilara Z. ^{[1
]}

Gazizov, Ilnaz M. ^{[2
]}

Zhuravleva, Margarita N. ^{[1
]}

Arkhipova, Svetlana S. ^{[1
]}

Golubenko, Maria A. ^{[1
]}

Gomzikova, Marina O. ^{[1
]}

Garanina, Ekaterina E. ^{[1
]}

Islamov, Rustem R. ^{[2
]}

Rizvanov, Albert A. ^{[1
]}

Salafutdinov, Ilnur I. ^{[1
,2
]}

机构：

[1] Kazan Volga Reg Fed Univ, Inst Fundamental Med & Biol, Kazan 420008, Russia

[2] Kazan State Med Univ, Dept Med Biol & Genet, Kazan 420012, Russia

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 05期

关键词：

human umbilical cord blood mononuclear cells; angiogenesis; recombinant adenoviruses; gene modification; transgene expression; VEGF; FGF2; SDF1; alpha; NUDE mice; Matrigel plugs; cytokine profile; ENDOTHELIAL GROWTH-FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; SOMATIC STEM-CELL; GENE-THERAPY; UNRELATED DONORS; BONE-MARROW; IN-VIVO; TRANSPLANTATION; ADENOVIRUS; VECTORS;

D O I：

10.3390/ijms24054396

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Stimulating the process of angiogenesis in treating ischemia-related diseases is an urgent task for modern medicine, which can be achieved through the use of different cell types. Umbilical cord blood (UCB) continues to be one of the attractive cell sources for transplantation. The goal of this study was to investigate the role and therapeutic potential of gene-engineered umbilical cord blood mononuclear cells (UCB-MC) as a forward-looking strategy for the activation of angiogenesis. Adenovirus constructs Ad-VEGF, Ad-FGF2, Ad-SDF1 alpha, and Ad-EGFP were synthesized and used for cell modification. UCB-MCs were isolated from UCB and transduced with adenoviral vectors. As part of our in vitro experiments, we evaluated the efficiency of transfection, the expression of recombinant genes, and the secretome profile. Later, we applied an in vivo Matrigel plug assay to assess engineered UCB-MC's angiogenic potential. We conclude that hUCB-MCs can be efficiently modified simultaneously with several adenoviral vectors. Modified UCB-MCs overexpress recombinant genes and proteins. Genetic modification of cells with recombinant adenoviruses does not affect the profile of secreted pro- and anti-inflammatory cytokines, chemokines, and growth factors, except for an increase in the synthesis of recombinant proteins. hUCB-MCs genetically modified with therapeutic genes induced the formation of new vessels. An increase in the expression of endothelial cells marker (CD31) was revealed, which correlated with the data of visual examination and histological analysis. The present study demonstrates that gene-engineered UCB-MC can be used to stimulate angiogenesis and possibly treat cardiovascular disease and diabetic cardiomyopathy.

引用

页数：19

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