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Angiogenesis. 2018 Aug;21(3):425-532. doi: 10.1007/s10456-018-9613-x.

Consensus guidelines for the use and interpretation of angiogenesis assays.

Author information

1
Molecular Pharmacology Group, School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, University of Lausanne, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. Patrycja.Nowak-Sliwinska@unige.ch.
2
Translational Research Center in Oncohaematology, University of Geneva, Geneva, Switzerland. Patrycja.Nowak-Sliwinska@unige.ch.
3
Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Helsinki, Finland.
4
Laboratory of Tumor Microenvironment and Therapeutic Resistance, Department of Oncology, VIB-Center for Cancer Biology, KU Leuven, Louvain, Belgium.
5
Department of Pathology, University of Washington, Seattle, WA, USA.
6
University of Wisconsin, Madison, WI, USA.
7
European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
8
Division of Vascular Oncology and Metastasis Research, German Cancer Research Center, Heidelberg, Germany.
9
German Cancer Consortium, Heidelberg, Germany.
10
Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
11
Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
12
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA.
13
Department of Neurological Surgery, Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
14
Angiogenesis and Tumor Microenvironment Laboratory (INSERM U1029), University Bordeaux, Pessac, France.
15
Vascular Biology Program and Department of Surgery, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
16
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
17
Department of Oncology, University of Torino, Turin, Italy.
18
Candiolo Cancer Institute-FPO-IRCCS, 10060, Candiolo, Italy.
19
Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
20
Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium.
21
Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium.
22
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
23
Department of Microscopic Morphology/Histology, Angiogenesis Research Center, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania.
24
Department of Molecular Biology, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
25
Ludwig Institute for Cancer Research, Department of Oncology, University of Lausanne, Lausanne, Switzerland.
26
Department of Medical Pharmacology and Physiology, University of Missouri, School of Medicine and Dalton Cardiovascular Center, Columbia, MO, USA.
27
School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland.
28
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
29
Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
30
Institute of Anatomy, University of Bern, Bern, Switzerland.
31
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
32
Emily Couric Cancer Center, The University of Virginia, Charlottesville, VA, USA.
33
Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
34
Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, Leuven, Belgium.
35
Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute, Leuven, Belgium.
36
University of California, San Diego, La Jolla, CA, USA.
37
Institute of Ophthalmology, University College London, London, UK.
38
Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
39
Metabolomics Expertise Center, VIB Center for Cancer Biology, VIB, Leuven, Belgium.
40
Department of Oncology, Metabolomics Expertise Center, KU Leuven, Leuven, Belgium.
41
Molecular Oncology Laboratories, Oxford University Department of Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
42
MCDB, University of California, Los Angeles, CA, USA.
43
Department of Cancer Biology, Metastasis Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
44
Department of Medical Biophysics, Biological Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
45
Department of Physiology and Biophysics, University of Illinois, Chicago, IL, USA.
46
Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
47
The George Washington University School of Medicine, Washington, DC, USA.
48
Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.
49
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
50
HistoGeneX, Antwerp, Belgium.
51
Department of Cardiac Surgery, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
52
Pathology and Laboratory Medicine Service, VA Puget Sound Health Care System, Seattle, WA, USA.
53
Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, Liège, Belgium.
54
Department of Biotechnology and Molecular Medicine, University of Eastern Finland, Kuopio, Finland.
55
Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden.
56
Department of oncology UNIL-CHUV, Ludwig Institute for Cancer Research Lausanne, Lausanne, Switzerland.
57
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund, Sweden.
58
Genitourinary Program, Indiana University-Simon Cancer Center, Indianapolis, IN, USA.
59
Medical Research Council Centre for Reproductive Health, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.
60
Department of Physiology, Maastricht University, Maastricht, The Netherlands.
61
Einthoven Laboratory for Experimental Vascular Medicine, Department Surgery, LUMC, Leiden, The Netherlands.
62
Laboratory of Immunopathology, Institute of Biology and Experimental Medicine, National Council of Scientific and Technical Investigations (CONICET), Buenos Aires, Argentina.
63
Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
64
National Cancer Institute "Giovanni Paolo II", Bari, Italy.
65
Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
66
Institute of Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, WWU, Münster, Germany.
67
Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH, USA.
68
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
69
Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre and The Sir Peter MacCallum, Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
70
Translational Cancer Research Unit, GZA Hospitals, Sint-Augustinus & University of Antwerp, Antwerp, Belgium.
71
Medical Faculty, University of Münster, Albert-Schweitzer-Campus 1, Münster, Germany.
72
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
73
Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. aw.griffioen@vumc.nl.

Abstract

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

KEYWORDS:

Angiogenesis; Aortic ring; Chorioallantoic membrane (CAM); Corneal angiogenesis; Endothelial cell migration; Hindlimb ischemia; Intussusceptive angiogenesis; Microfluidic; Myocardial angiogenesis; Plug assay; Proliferation; Recombinant proteins; Retinal vasculature; Tip cells; Vascular network; Vessel co-option; Zebrafish

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