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      New artery of knowledge: 3D models of angiogenesis

      review-article
      1 , 1 , 1 , 2
      Vascular Biology
      Bioscientifica Ltd
      angiogenesis, endothelial cells, 3D assays

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          Abstract

          Angiogenesis and vasculogenesis are complex processes by which new blood vessels are formed and expanded. They play a pivotal role not only in physiological development and growth and tissue and organ repair, but also in a range of pathological conditions, from tumour formation to chronic inflammation and atherosclerosis. Understanding the multistep cell-differentiation programmes and identifying the key molecular players of physiological angiogenesis/vasculogenesis are critical to tackle pathological mechanisms. While many questions are yet to be answered, increasingly sophisticated in vitro, in vivo and ex vivo models of angiogenesis/vasculogenesis, together with cutting-edge imaging techniques, allowed for recent major advances in the field. This review aims to summarise the three-dimensional models available to study vascular network formation and to discuss advantages and limitations of the current systems.

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          Most cited references61

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          The zebrafish reference genome sequence and its relationship to the human genome.

          Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
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            Human blood vessel organoids as a model of diabetic vasculopathy

            The increasing prevalence of diabetes has resulted in a global epidemic1. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and amputation of lower limbs. These are often caused by changes in blood vessels, such as the expansion of the basement membrane and a loss of vascular cells2-4. Diabetes also impairs the functions of endothelial cells5 and disturbs the communication between endothelial cells and pericytes6. How dysfunction of endothelial cells and/or pericytes leads to diabetic vasculopathy remains largely unknown. Here we report the development of self-organizing three-dimensional human blood vessel organoids from pluripotent stem cells. These human blood vessel organoids contain endothelial cells and pericytes that self-assemble into capillary networks that are enveloped by a basement membrane. Human blood vessel organoids transplanted into mice form a stable, perfused vascular tree, including arteries, arterioles and venules. Exposure of blood vessel organoids to hyperglycaemia and inflammatory cytokines in vitro induces thickening of the vascular basement membrane. Human blood vessels, exposed in vivo to a diabetic milieu in mice, also mimic the microvascular changes found in patients with diabetes. DLL4 and NOTCH3 were identified as key drivers of diabetic vasculopathy in human blood vessels. Therefore, organoids derived from human stem cells faithfully recapitulate the structure and function of human blood vessels and are amenable systems for modelling and identifying the regulators of diabetic vasculopathy, a disease that affects hundreds of millions of patients worldwide.
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              THE CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTES

              An in vitro technique is described for assessing the chemotactic activity of soluble substances on motile cells. Antibody-antigen mixtures when incubated (37°C) in medium containing fresh (i.e. non-inactivated) normal rabbit serum exert a strong chemotactic effect on rabbit polymorphonuclear leucocytes. Results are described which indicate that, when antibody-antigen complexes are incubated (37°C) in fresh serum, a heat-stable (56°C) substance (or substances) is produced which acts directly as a chemotactic stimulus on the polymorphs. This heat-stable chemotactic substance is not produced when antibody-antigen complexes are incubated in serum which has been heated at 56°C for 30 minutes.
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                Author and article information

                Journal
                Vasc Biol
                Vasc Biol
                vb
                Vascular Biology
                Bioscientifica Ltd (Bristol )
                2516-5658
                2019
                03 December 2019
                : 1
                : 1
                : H135-H143
                Affiliations
                [1 ]National Heart and Lung Institute , Imperial College London, London, UK
                [2 ]Heart and Vascular Center , Semmelweis University, Budapest, Hungary
                Author notes
                Correspondence should be addressed to G Foldes: g.foldes@ 123456imperial.ac.uk
                Article
                VB-19-0026
                10.1530/VB-19-0026
                7439835
                16a3cf34-96c8-4339-81eb-3d74ed95ca6c
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 27 November 2019
                : 03 December 2019
                Categories
                Mini Review

                angiogenesis,endothelial cells,3d assays
                angiogenesis, endothelial cells, 3d assays

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