Stealing VEGF from Thy Neighbor

Domigan, Courtney K.; Iruela‐Arispe, M. Luisa

doi:10.1016/j.cell.2014.10.008

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…The fraction of tip cells selected depends on the rate at which VEGF is introduced from adjacent tissues: a stronger flux of VEGF can sustain more tip cells in the final pattern. From a multicellular perspective, this hypothesis, that limitations of VEGF control tip cell density, is consistent with previous experiment observations showing that VEGF receptors (VEGFR2) displayed by adjacent neurons act as strong sinks for VEGF that limit local formation of endothelial tip cells (28,29).…”

Section: Another Route To Predicting Variable Numbers Of Tip Cells Sesupporting

confidence: 91%

A VEGF reaction-diffusion mechanism that selects variable densities of endothelial tip cells

Bedell

Stroock

2019

Preprint

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The patterned differentiation of endothelial cells into tip and stalk cells represents an important step in the process of angiogenic sprouting. Vascular biologists hypothesize that changes in the density and overall structure of the vasculature can be traced in part to changes in the number of tip cells selected in the endothelium prior to sprout formation.However, the dominant hypotheses for tip cell selection invoke lateral inhibition via Notch; this juxtacrine mechanism predicts that a fixed fraction of endothelial cells become tip cells through a pattern-forming instability. Here, we present and analyze a hypothetical mechanism for tip cell selection that is based on endothelial competition for diffusible vascular endothelial growth factor (VEGF); this mechanism predicts that variable densities of tip cells emerge depending on the local (paracrine) production rate of VEGF. First, we hypothesize a network of VEGF signaling and trafficking based on previous experimental findings that could allow internalization of VEGF to occur with positive feedback. We formalize the hypothesis into a set of nonlinear ordinary differential equations and perform linear stability analysis to elucidate a general criterion for tip cell pattern formation under the mechanism.We use numerical integration to explore the nonlinear dynamics and final steady-states of tip cell patterns under this mechanism; the observed density of tip cells can be tuned from 10% to 84%. We conclude with proposals of future experiments and computational studies to explore how competitive consumption of diffusible VEGF may play a role in determining vascular structure.

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Section: Another Route To Predicting Variable Numbers Of Tip Cells Sesupporting

confidence: 91%

A VEGF reaction-diffusion mechanism that selects variable densities of endothelial tip cells

Bedell

Stroock

2019

Preprint

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“…For these growth factors, (i) VEGF is a central regulator of angiogenesis. It maintains endothelial cell integrity and is a potent mitogen for micro‐ and macrovascular endothelial cells . The VEGF content retained in the AVM was lower than that in the SIS.…”

Section: Discussionmentioning

confidence: 98%

“…It maintains endothelial cell integrity and is a potent mitogen for micro-and macrovascular endothelial cells. 15,16 The VEGF content retained in the AVM was lower than that in the SIS. (ii) FGF is a very effective angiogenic cytokine and an important mitogenic and differentiationinducing factor with broad biological functions in the cell differentiation process.…”

Section: Discussionmentioning

confidence: 99%

A new material for tissue engineered vagina reconstruction: Acellular porcine vagina matrix

Zhang

et al. 2017

J Biomedical Materials Res

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Acellular matrix materials have been widely used to repair various tissues and organs. According to the plastic principle, when a part of the body is lost, it should be replaced with a similar material. Therefore, the use of a homologous organ-specific acellular vaginal tissue in vagina reconstruction repair surgery may show good results. However, the acellular vagina matrix (AVM) form large vertebrates is difficult to isolate. In this study, we described a multistep method to prepare porcine AVM and evaluated the efficacy of acellularization. We also investigated the biomechanical properties, biological activity elements, and biocompatibility of the porcine AVM. We then used this material to reconstruct a rat vagina and performed further morphologic and functional analyses. Small intestinal submucosa (SIS), which is a commonly used acellular matrix material, was used in a control group. Histological examination, DNA content analysis, and agarose gel electrophoresis revealed that the decellularization procedure was effective. The AVM had acceptable biomechanical properties and sufficient growth factor production (VEGF, FGF, TGF-β1, and PDGF-BB) compared with that of the SIS. Subcutaneous transplantation in rats showed that the AVM had good biocompatibility. The tissue-engineered vagina using the AVM more resembled normal-appearing tissue than did that using SIS following morphologic and functional analyses. The AVM has great potential for application in vaginal reconstructive surgery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1949-1959, 2017.

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“…In neuron-specific deletions of Vegfr2 (Pax6 α-Cre, Vegfr2 floxed) , free VEGF proteins are markedly increased due to neurons insufficiently engulfing VEGF, which result in misdirected vertical angiogenic growth toward neurons and dense intraretinal vascular plexus. However, this mutant mouse has no MNV3 lesion ( Domigan and Iruela-Arispe, 2014 ; Okabe et al, 2014 ). A major difference between the sVEGFR1 deletion model ( Luo et al, 2013 ) and the Vegfr2 deletion model ( Okabe et al, 2014 ) is the Cre mouse line, iCre-75 only expresses in rods, but Pax6 α-Cre can express in all retinal cells ( Marquardt et al, 2001 ).…”

Section: Animal Models Of Type 3 Macular Neovascularizationmentioning

confidence: 92%

Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization

Wei

Chen

et al. 2021

Front. Neurosci.

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Type 3 macular neovascularization (MNV3), or retinal angiomatous proliferation (RAP), is a distinct type of neovascular age-related macular degeneration (AMD), which is a leading cause of vision loss in older persons. During the past decade, systematic investigation into the clinical, multimodal imaging, and histopathological features and therapeutic outcomes has provided important new insight into this disease. These studies favor the retinal origin of MNV3 and suggest the involvement of retinal hypoxia, inflammation, von Hippel–Lindau (VHL)–hypoxia-inducible factor (HIF)–vascular endothelial growth factor (VEGF) pathway, and multiple cell types in the development and progression of MNV3. Several mouse models, including the recently built Rb/p107/Vhl triple knockout mouse model by our group, have induced many of the histological features of MNV3 and provided much insight into the underlying pathological mechanisms. These models have revealed the roles of retinal hypoxia, inflammation, lipid metabolism, VHL/HIF pathway, and retinoblastoma tumor suppressor (Rb)–E2F cell cycle pathway in the development of MNV3. This article will summarize the clinical, multimodal imaging, and pathological features of MNV3 and the diversity of animal models that exist for MNV3, as well as their strengths and limitations.

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Stealing VEGF from Thy Neighbor

Cited by 8 publications

References 10 publications

A VEGF reaction-diffusion mechanism that selects variable densities of endothelial tip cells

A VEGF reaction-diffusion mechanism that selects variable densities of endothelial tip cells

A new material for tissue engineered vagina reconstruction: Acellular porcine vagina matrix

Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization

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