Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays

Angiogenesis is a highly ordered physiological process regulated by the interaction of endothelial cells with an extensive variety of growth factors, extracellular matrix components and mechanical stimuli. One of the most important challenges in tissue engineering is the rapid neovascularization of...

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Main Authors: Serkan Dikici, Betül Aldemir Dikici, Shirin Issa Bhaloo, Mercedes Balcells, Elazer R. Edelman, Sheila MacNeil, Gwendolen C. Reilly, Colin Sherborne, Frederik Claeyssens
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-01-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fbioe.2019.00451/full
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author Serkan Dikici
Serkan Dikici
Betül Aldemir Dikici
Betül Aldemir Dikici
Betül Aldemir Dikici
Shirin Issa Bhaloo
Mercedes Balcells
Mercedes Balcells
Elazer R. Edelman
Elazer R. Edelman
Sheila MacNeil
Gwendolen C. Reilly
Gwendolen C. Reilly
Colin Sherborne
Frederik Claeyssens
Frederik Claeyssens
author_facet Serkan Dikici
Serkan Dikici
Betül Aldemir Dikici
Betül Aldemir Dikici
Betül Aldemir Dikici
Shirin Issa Bhaloo
Mercedes Balcells
Mercedes Balcells
Elazer R. Edelman
Elazer R. Edelman
Sheila MacNeil
Gwendolen C. Reilly
Gwendolen C. Reilly
Colin Sherborne
Frederik Claeyssens
Frederik Claeyssens
author_sort Serkan Dikici
collection DOAJ
description Angiogenesis is a highly ordered physiological process regulated by the interaction of endothelial cells with an extensive variety of growth factors, extracellular matrix components and mechanical stimuli. One of the most important challenges in tissue engineering is the rapid neovascularization of constructs to ensure their survival after transplantation. To achieve this, the use of pro-angiogenic agents is a widely accepted approach. The study of angiogenesis has gained momentum over the last two decades. Although there are various in vitro, ex vivo, and in vivo angiogenesis models that enable testing of newly discovered pro-angiogenic agents, the problem with researching angiogenesis is the choice of the most appropriate assay. In vivo assays are the most representative and reliable models, but they are expensive, time-consuming and can cause ethical concerns whereas in vitro assays are relatively inexpensive, practical, and reproducible, but they are usually lack of enabling the study of more than one aspect of angiogenesis, and they do not fully represent the complexity of physiological angiogenesis. Therefore, there is a need for the development of an angiogenesis model that allows the study of angiogenesis under physiologically more relevant, dynamic conditions without causing ethical concerns. Accordingly, in this study, we developed 3D in vitro dynamic angiogenesis model, and we tested the angiogenic potential of 2-deoxy-D-ribose (2dDR) in comparison with vascular endothelial growth factor (VEGF) using newly developed in vitro 3D dynamic model and well-established in vitro models. Our results obtained using conventional in vitro assays demonstrated that 2dDR promoted proliferation, migration and tube formation of human aortic endothelial cells (HAECs) in a dose-dependent manner. Then, the angiogenic activity of 2dDR was further assessed using the newly developed 3D in vitro model, which enabled the monitoring of cell proliferation and infiltration simultaneously under dynamic conditions. Our results showed that the administration of 2dDR and VEGF significantly enhanced the outgrowth of HAECs and the cellular density under either static or dynamic conditions.
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spelling doaj.art-2ba15d288e2742fc92d0303c01a577862022-12-21T20:45:06ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-01-01710.3389/fbioe.2019.00451497474Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro AssaysSerkan Dikici0Serkan Dikici1Betül Aldemir Dikici2Betül Aldemir Dikici3Betül Aldemir Dikici4Shirin Issa Bhaloo5Mercedes Balcells6Mercedes Balcells7Elazer R. Edelman8Elazer R. Edelman9Sheila MacNeil10Gwendolen C. Reilly11Gwendolen C. Reilly12Colin Sherborne13Frederik Claeyssens14Frederik Claeyssens15Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield, United KingdomInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United StatesDepartment of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield, United KingdomInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United StatesDepartment of Materials Science and Engineering, INSIGNEO Institute for In Silico Medicine, University of Sheffield, Sheffield, United KingdomInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United StatesInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United StatesBioengineering Department, Institut Quimic de Sarria, Ramon Llull University, Barcelona, SpainInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United StatesDivision of Cardiovascular Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United StatesDepartment of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield, United KingdomDepartment of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield, United KingdomDepartment of Materials Science and Engineering, INSIGNEO Institute for In Silico Medicine, University of Sheffield, Sheffield, United KingdomDepartment of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield, United KingdomDepartment of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield, United KingdomDepartment of Materials Science and Engineering, INSIGNEO Institute for In Silico Medicine, University of Sheffield, Sheffield, United KingdomAngiogenesis is a highly ordered physiological process regulated by the interaction of endothelial cells with an extensive variety of growth factors, extracellular matrix components and mechanical stimuli. One of the most important challenges in tissue engineering is the rapid neovascularization of constructs to ensure their survival after transplantation. To achieve this, the use of pro-angiogenic agents is a widely accepted approach. The study of angiogenesis has gained momentum over the last two decades. Although there are various in vitro, ex vivo, and in vivo angiogenesis models that enable testing of newly discovered pro-angiogenic agents, the problem with researching angiogenesis is the choice of the most appropriate assay. In vivo assays are the most representative and reliable models, but they are expensive, time-consuming and can cause ethical concerns whereas in vitro assays are relatively inexpensive, practical, and reproducible, but they are usually lack of enabling the study of more than one aspect of angiogenesis, and they do not fully represent the complexity of physiological angiogenesis. Therefore, there is a need for the development of an angiogenesis model that allows the study of angiogenesis under physiologically more relevant, dynamic conditions without causing ethical concerns. Accordingly, in this study, we developed 3D in vitro dynamic angiogenesis model, and we tested the angiogenic potential of 2-deoxy-D-ribose (2dDR) in comparison with vascular endothelial growth factor (VEGF) using newly developed in vitro 3D dynamic model and well-established in vitro models. Our results obtained using conventional in vitro assays demonstrated that 2dDR promoted proliferation, migration and tube formation of human aortic endothelial cells (HAECs) in a dose-dependent manner. Then, the angiogenic activity of 2dDR was further assessed using the newly developed 3D in vitro model, which enabled the monitoring of cell proliferation and infiltration simultaneously under dynamic conditions. Our results showed that the administration of 2dDR and VEGF significantly enhanced the outgrowth of HAECs and the cellular density under either static or dynamic conditions.https://www.frontiersin.org/article/10.3389/fbioe.2019.00451/fullangiogenesisvascular endothelial growth factor (VEGF)2-deoxy-D-ribose (2dDR)thymidine phosphorylase (TP)angiogenesis assaysshear stress
spellingShingle Serkan Dikici
Serkan Dikici
Betül Aldemir Dikici
Betül Aldemir Dikici
Betül Aldemir Dikici
Shirin Issa Bhaloo
Mercedes Balcells
Mercedes Balcells
Elazer R. Edelman
Elazer R. Edelman
Sheila MacNeil
Gwendolen C. Reilly
Gwendolen C. Reilly
Colin Sherborne
Frederik Claeyssens
Frederik Claeyssens
Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays
Frontiers in Bioengineering and Biotechnology
angiogenesis
vascular endothelial growth factor (VEGF)
2-deoxy-D-ribose (2dDR)
thymidine phosphorylase (TP)
angiogenesis assays
shear stress
title Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays
title_full Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays
title_fullStr Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays
title_full_unstemmed Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays
title_short Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays
title_sort assessment of the angiogenic potential of 2 deoxy d ribose using a novel in vitro 3d dynamic model in comparison with established in vitro assays
topic angiogenesis
vascular endothelial growth factor (VEGF)
2-deoxy-D-ribose (2dDR)
thymidine phosphorylase (TP)
angiogenesis assays
shear stress
url https://www.frontiersin.org/article/10.3389/fbioe.2019.00451/full
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