Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells
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 stud...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/5/4396 |
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| author | Dilara Z. Gatina Ilnaz M. Gazizov Margarita N. Zhuravleva Svetlana S. Arkhipova Maria A. Golubenko Marina O. Gomzikova Ekaterina E. Garanina Rustem R. Islamov Albert A. Rizvanov Ilnur I. Salafutdinov |
| author_facet | Dilara Z. Gatina Ilnaz M. Gazizov Margarita N. Zhuravleva Svetlana S. Arkhipova Maria A. Golubenko Marina O. Gomzikova Ekaterina E. Garanina Rustem R. Islamov Albert A. Rizvanov Ilnur I. Salafutdinov |
| author_sort | Dilara Z. Gatina |
| collection | DOAJ |
| description | 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-SDF1α, 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. |
| first_indexed | 2024-03-11T07:23:14Z |
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| id | doaj.art-15f270e8d6cd4704b9cc13e7878f7ebb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T07:23:14Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-15f270e8d6cd4704b9cc13e7878f7ebb2023-11-17T07:47:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245439610.3390/ijms24054396Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear CellsDilara Z. Gatina0Ilnaz M. Gazizov1Margarita N. Zhuravleva2Svetlana S. Arkhipova3Maria A. Golubenko4Marina O. Gomzikova5Ekaterina E. Garanina6Rustem R. Islamov7Albert A. Rizvanov8Ilnur I. Salafutdinov9Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, RussiaDepartment of Medical Biology and Genetics, Kazan State Medical University, 420012 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, RussiaDepartment of Medical Biology and Genetics, Kazan State Medical University, 420012 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, RussiaStimulating 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-SDF1α, 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.https://www.mdpi.com/1422-0067/24/5/4396human umbilical cord blood mononuclear cellsangiogenesisrecombinant adenovirusesgene modificationtransgene expressionVEGF |
| spellingShingle | Dilara Z. Gatina Ilnaz M. Gazizov Margarita N. Zhuravleva Svetlana S. Arkhipova Maria A. Golubenko Marina O. Gomzikova Ekaterina E. Garanina Rustem R. Islamov Albert A. Rizvanov Ilnur I. Salafutdinov Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells International Journal of Molecular Sciences human umbilical cord blood mononuclear cells angiogenesis recombinant adenoviruses gene modification transgene expression VEGF |
| title | Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells |
| title_full | Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells |
| title_fullStr | Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells |
| title_full_unstemmed | Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells |
| title_short | Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells |
| title_sort | induction of angiogenesis by genetically modified human umbilical cord blood mononuclear cells |
| topic | human umbilical cord blood mononuclear cells angiogenesis recombinant adenoviruses gene modification transgene expression VEGF |
| url | https://www.mdpi.com/1422-0067/24/5/4396 |
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