Combination of Vascular Endothelial Growth Factor (VEGF) and Thymidine Phosphorylase (TP) to Improve Angiogenic Gene Therapy

Bouis, Diane; Boelens, Mirjam C.; Peters, Erna; Koolwijk, Pieter; Stob, Gerrie J.; Kema, Ido P.; Klinkenberg, Marco; Mulder, Nanno; Hospers, Geke A.P.

doi:10.1023/b:agen.0000021389.49659.31

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…In summary, we have shown that endothelial cells grown in three-dimensional spheroid culture and co-implanted with hOBs into PBCB-scaffolds, organize in vivo into tubes and form dense functional vessel networks. [15][16][17], gene therapeutic approaches [18,19] or cell-based therapies using endothelial cells [9,10]. In this study, we have employed a three-dimensional endothelial cell spheroid system to improve in vivo vascularization in bone tissue constructs.…”

Section: Resultsmentioning

confidence: 99%

“…Without the generation of a functional vascular network, implanted cells will undergo apoptosis due to limitations in oxygen and nutrient supply. Multifarious strategies to induce therapeutic angiogenesis are described and comprise the use of various recombinant angiogenic growth factors such as VEGF and bFGF [15–17], gene therapeutic approaches [18, 19] or cell‐based therapies using endothelial cells [9, 10]. In this study, we have employed a three‐dimensional endothelial cell spheroid system to improve in vivo vascularization in bone tissue constructs.…”

Section: Discussionmentioning

confidence: 99%

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In vivo engineering of a human vasculature for bone tissue engineering applications

Steffens

Wenger

Stärk

et al. 2009

J Cellular Molecular Medi

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The neovascularization of three-dimensional voluminous tissues, such as bone, represents an important challenge in tissue engineering applications. The formation of a preformed vascular plexus could maintain cell viability and promote vascularization after transplantation. We have developed a three-dimensional spheroidal coculture system consisting of human primary endothelial cells and human primary osteoblasts (hOBs) to improve angiogenesis in bone tissue engineering applications. In this study, we investigated the survival and vascularization of the engineered implants in vivo. Endothelial cell spheroids were cocultured with hOBs in fibrin and seeded into scaffolds consisting of processed bovine cancellous bone (PBCB). The cell-seeded scaffolds were evaluated for their angiogenic potential in two different in vivo assays: the chick embryo chorioallantoic membrane (CAM) model and the severe combined immunodeficiency disorder (SCID) mouse model. In both assays, the development of a complex three-dimensional network of perfused human neovessels could be detected. After subcutaneous implantation into immunodeficient mice, the newly formed human vasculature was stabilized by the recruitment of murine smooth muscle α-actin-positive mural cells and anastomoses with the mouse vasculature. We conclude that this endothelial cell spheroid system can be used to create a network of functional perfused blood vessels in vivo. The finding that this process takes place with high efficacy in the presence of co-implanted primary osteoblasts and in an osteoconductive environment provided by the PBCB scaffold, suggests that this system may be suitable for improving vascularization in bone tissue engineering.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In vivo engineering of a human vasculature for bone tissue engineering applications

Steffens

Wenger

Stärk

et al. 2009

J Cellular Molecular Medi

View full text Add to dashboard Cite

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“…Without the generation of a functional vascular network, the implanted cells will undergo apoptosis due to limitations in oxygen and nutrient supply. Strategies to generate perfused microvessels in tissue engineering applications are multifarious and comprise the use of in vitro fabricated perfused microvessels [Neumann et al, 2003], the induction of host blood vessel formation by various angiogenic growth factors such as VEGF and bFGF [Pieper et al, 2002;Perets et al, 2003;Zisch et al, 2003] or gene therapeutic approaches to induce neoangiogenesis [Rebar et al, 2002;Bouis et al, 2003; for a review, see Dor et al, 2003]. In this study, we have employed a cell-based approach to improve angiogenesis in tissue-engineered constructs, using endothelial cells grown in form of three-dimensional spheroids.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterization of a Spheroidal Coculture Model of Endothelial Cells and Fibroblasts for Improving Angiogenesis in Tissue Engineering

Wenger

Kowalewski

Stahl

et al. 2005

Cells Tissues Organs

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Neovascularization is a critical step in tissue engineering applications since implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of central tissues. We have developed a three-dimensional spheroidal coculture system consisting of human umbilical vein endothelial cells (HUVECs) and human primary fibroblasts (hFBs) to improve angiogenesis in tissue engineering applications. Morphological analysis of cryosections from HUVEC/hFB cospheroids revealed a characteristic temporal and spatial organization with HUVECs located in the center of the cospheroid and a peripheral localization of fibroblasts. In coculture spheroids, the level of apoptosis of endothelial cells was strongly decreased upon cocultivation with fibroblasts. Collagen-embedded HUVEC spheroids develop numerous lumenized capillary-like sprouts. This was also apparent for HUVEC/hFB cospheroids, albeit to a lesser extent. Quantification of cumulative sprout length revealed an approximately 35% reduction in endothelial cell sprouting upon cocultivation with fibroblasts in cospheroids. The slight reduction in endothelial cell sprouting was not mediated by a paracrine mechanism but is most likely due to the formation of heterogenic cell contacts between HUVECs and hFBs within the cospheroid. The model system introduced in this study is suitable for the development of a preformed lumenized capillary-like network ex vivo and may therefore be useful for improving angiogenesis in in vivo tissue engineering applications.

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“…Endothelial cells are involved in the inner cell lining of all blood vessels [1,2]. It is important to mention that endothelial cells in response to tissue injury or hypoxic conditions can form new vessels through a differentiation process called angiogenesis [3,4].…”

Section: Introductionmentioning

confidence: 99%

Interaction of Some Amino-Nitrile Derivatives with Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) Using a Theoretical Model

et al. 2023

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Background Some studies indicate that the angiogenesis process is related to vascular endothelial growth factor, which can interact with endothelial cell surface receptors (VEGF-R1, VEGF-R2, and VEGF-R3); this biochemical process and other factors result in the promotion and growth of new blood vessels under normal conditions. However, some studies indicate that this phenomenon could also occur in cancer cells. It is important to mention that some amino derivatives have been prepared as VEGF-R1 inhibitors; however, their interaction with VEGF-R1 is not clear, perhaps due to different experimental approaches or differences in their chemical structure. Objective The aim of this study was to evaluate the theoretical interaction of several amino-nitrile derivatives (Compounds 1 to 38) with VEGF-R1. Methods The theoretical interaction of amino-nitrile derivatives with VEGF-R1 was carried out using the 3hng protein as the theoretical model. In addition, cabozantinib, pazopanib, regorafenib, and sorafenib were used as controls in the DockingServer program. Results The results showed different amino acid residues involved in the interaction of amino-nitrile derivatives with the 3hng protein surface compared with the controls. In addition, the inhibition constant (Ki) was lower for Compounds 10 and 34 than for cabozantinib. Other results show that Ki for Compounds 9, 10, 14, 27–29 and 34–36 was lower in comparison with pazopanib, regorafenib, and sorafenib. Conclusions All theoretical data suggest that amino-nitrile derivatives could produce changes in the growth of some cancer cell lines through VEGFR-1 inhibition. Therefore, these amino-nitrile derivatives could be a therapeutic alternative to treat some types of cancer.

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Combination of Vascular Endothelial Growth Factor (VEGF) and Thymidine Phosphorylase (TP) to Improve Angiogenic Gene Therapy

Cited by 6 publications

References 41 publications

In vivo engineering of a human vasculature for bone tissue engineering applications

In vivo engineering of a human vasculature for bone tissue engineering applications

Development and Characterization of a Spheroidal Coculture Model of Endothelial Cells and Fibroblasts for Improving Angiogenesis in Tissue Engineering

Interaction of Some Amino-Nitrile Derivatives with Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) Using a Theoretical Model

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