Stimulation of functional vessel growth by gene therapy

2010 ◽  
Vol 2 (2-3) ◽  
pp. 102-112 ◽  
Author(s):  
Petra Korpisalo ◽  
Seppo Ylä-Herttuala
2000 ◽  
Vol 278 (2) ◽  
pp. H404-H411 ◽  
Author(s):  
Deborah H. Damon

Sympathetic nerves are purported to stimulate blood vessel growth. The mechanism(s) underlying this stimulation has not been determined. With use of an in vitro coculture model, the present study tests the hypothesis that sympathetic neurons stimulate the growth of vascular smooth muscle (VSM) and evaluates potential mechanisms mediating this stimulation. Sympathetic neurons isolated from superior cervical ganglia (SCG) stimulated the growth of VSM. Growth of VSM in the presence of SCG (856 ± 81%) was significantly greater than that in the absence of SCG (626 ± 66%, P < 0.05). SCG did not stimulate VSM growth in transwell cocultures. An antibody that neutralized the activity of transforming growth factor-β2 (TGF-β2) inhibited SCG stimulation of VSM growth in coculture. SCG stimulation of VSM growth was also inhibited by an endothelin A receptor antagonist. These data suggest novel mechanisms for sympathetic modulation of vascular growth that may play a role in the physiological and/or pathological growth of the vasculature.


2018 ◽  
Vol 71 (11) ◽  
pp. A271
Author(s):  
Maurits Hollander ◽  
Matthijs Jansen ◽  
Tineke Van der Pouw-Kraan ◽  
Edward Dolk ◽  
Paul Knaapen ◽  
...  

1979 ◽  
Vol 26 (4) ◽  
pp. 430-436 ◽  
Author(s):  
Kewal K. Thakral ◽  
William H. Goodson ◽  
Thomas K. Hunt

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 432 ◽  
Author(s):  
Ilnur I. Salafutdinov ◽  
Ilnaz M. Gazizov ◽  
Dilara K. Gatina ◽  
Ruslan I. Mullin ◽  
Alexey A. Bogov ◽  
...  

Several methods for the stimulation of skin wound repair have been proposed over the last few decades. The most promising among them are gene and stem cell therapy. Our present experiments combined several approaches via the application of human umbilical cord blood mononuclear cells (hUCB-MC) that were transfected with pBud-VEGF165-FGF2 plasmid (gene-cell therapy) and direct gene therapy using pBud-VEGF165-FGF2 plasmid to enhance healing of full thickness skin wounds in rats. The dual expression cassette plasmid pBud-VEGF165-FGF2 encodes both VEGF and FGF2 therapeutic genes, expressing pro-angiogenic growth factors. Our results showed that, with two weeks post-transplantation, some transplanted cells still retained expression of the stem cell and hematopoietic markers C-kit and CD34. Other transplanted cells were found among keratinocytes, hair follicle cells, endothelial cells, and in the derma. PCNA expression studies revealed that transplantation of transfected cells terminated proliferative processes in regenerating wounds earlier than transplantation of untransfected cells. In the direct gene therapy group, four days post-operatively, the processes of flap revascularization, while using Easy LDI Microcirculation Camera, was higher than in control wounded skin. We concluded that hUCB-MC can be used for the treatment of skin wounds and transfection these cells with VEGF and FGF2 genes enhances their regenerative abilities. We also concluded that the application of pBud-VEGF165-FGF2 plasmids is efficient for the direct gene therapy of skin wounds by stimulation of wound revascularization.


Author(s):  
Sanna Koponen ◽  
Emmi Kokki ◽  
Kati Kinnunen ◽  
Seppo Ylä-Herttuala

Pathological vessel growth harms vision and may finally lead to vision loss. Anti-angiogenic gene therapy with viral vectors for ocular neovascularization has shown great promise in pre-clinical studies. Most of the studies has conducted with different adeno-associate serotype vectors. In addition, Adeno and lentivirus vectors have been used. Therapy has targeted to block vascular endothelial growth factors or other pro-angiogenic factors. Clinical trials of intraocular gene therapy for neovascularization have shown the treatment to be safe without severe adverse events or systemic effects. Nevertheless, clinical studies have not proceeded phase 2 trials further.


Author(s):  
Katsu Takahashi ◽  
Honoka Kiso ◽  
Kazuyuki Saito ◽  
Yumiko Togo ◽  
Hiroko Tsukamoto ◽  
...  

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