journal article·2020-01-31Open access

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

Diana J. Medina-Leyte, Mayra Domínguez-Pérez, Ingrid Mercado, María T. Villarreal-Molina, Leonor Jacobo-Albavera

Applied Sciences· Volume 10· Issue 3

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide, and extensive research has been performed to understand this disease better, using various experimental models. The endothelium plays a crucial role in the development of CVD, since it is an interface between bloodstream components, such as monocytes and platelets, and other arterial wall components. Human umbilical vein endothelial cell (HUVEC) isolation from umbilical cord was first described in 1973. To date, this model is still widely used because of the high HUVEC isolation success rate, and because HUVEC are an excellent model to study a broad array of diseases, including cardiovascular and metabolic diseases. We here review the history of HUVEC isolation, the HUVEC model over time, HUVEC culture characteristics and conditions, advantages and disadvantages of this model and finally, its applications in the area of cardiovascular diseases.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · Angiogenesis and VEGF in Cancer · Coronary Interventions and Diagnostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Laboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica, Tlalpan, Ciudad de México 14610, Mexico

Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México 04510, Mexico

Departamento de Ingeniería Celular y Biocatálisis; Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico

References (100+)

Show source-provided references
1. Epigenetic Biomarkers in Cardiovascular Diseases10.3389/fgene.2019.00950 ↗
2. Targeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation10.1155/2019/8563845 ↗
4. Maamoun, H., Abdelsalam, S.S., Zeidan, A., Korashy, H.M., and Agouni, A. (2019). Endoplasmic Reticulum Stress: A Critical Molecular Driver of Endothelial Dysfunction and Cardiovascular Disturbances Associated with Diabetes. Int. J. Mol. Sci., 20.10.3390/ijms20071658 ↗
5. Shear stress regulates endothelial microparticle release10.1161/CIRCRESAHA.112.300818 ↗
6. microRNA-338-3p promotes ox-LDL-induced endothelial cell injury through targeting BAMBI and activating TGF-β/Smad pathway10.1002/jcp.27814 ↗
7. Alternatives to animal testing: A review10.1016/j.jsps.2013.11.002 ↗
8. Animal models are essential to biological research: Issues and perspectives10.4155/fso.15.63 ↗
9. In vitro models, in vivo models, and pharmacokinetics: What can we learn from in vitro models?10.1086/321850 ↗
10. Studying the influence of angiogenesis in in vitro cancer model systems10.1016/j.addr.2015.11.004 ↗
11. A protocol for isolation and culture of human umbilical vein endothelial cells10.1038/nprot.2007.54 ↗
12. A human vascular endothelial cell model to study angiogenesis and tumorigenesis10.1093/carcin/19.4.673 ↗
13. Human vascular endothelial cells: A model system for studying vascular inflammation in diabetes and atherosclerosis10.1007/s11892-011-0182-2 ↗
14. Development of an in vitro model for vascular injury with human endothelial cells
15. In vitro models for assessing the potential cardiovascular disease risk associated with cigarette smoking10.1016/j.tiv.2012.08.018 ↗
16. Carlson, B.M. (2014). Establishment of the Basic Embryonic Body Plan. Human Embryology and Developmental Biology, Elsevier. [5th ed.].10.1016/B978-1-4557-2794-0.00006-1 ↗
17. Concise review: Human umbilical cord stroma with regard to the source of fetus-derived stem cells10.1634/stemcells.2007-0417 ↗
18. Wharton’s Jelly-Derived Mesenchymal Stem Cells: Phenotypic Characterization and Optimizing Their Therapeutic Potential for Clinical Applications10.3390/ijms140611692 ↗
19. Study on myofibroblast differentiation in the stromal cells of Wharton’s jelly: Expression and localization of alpha-smooth muscle actin10.1016/S0378-3782(97)00123-0 ↗
20. Human umbilical cord matrix stem cells: Preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease10.1634/stemcells.2005-0330 ↗
21. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord10.1634/stemcells.2004-0013 ↗
22. Organotypic culture and surface plantation using umbilical cord epithelial cells: Morphogenesis and expression of differentiation markers mimicking cutaneous epidermis10.1016/j.jdermsci.2004.06.003 ↗
23. Stem cell characteristics of amniotic epithelial cells10.1634/stemcells.2004-0357 ↗
24. Expression of epithelial markers by human umbilical cord stem cells. A topographical analysis10.1016/j.placenta.2014.09.007 ↗
25. Wharton’s Jelly stem cells: Future clinical applications10.1016/j.placenta.2011.06.010 ↗
26. Tissue engineering from Adam to the zygote: Historical reflections10.1007/s003450050015 ↗
27. Endothelium in tissue cultures10.1002/aja.1000300104 ↗
28. Culture of human endothelial cells derived from umbilical veins10.1172/JCI107470 ↗
29. Human vascular endothelial cells in culture. Growth and DNA synthesis10.1083/jcb.60.3.673 ↗
30. Vascular endothelium as a regulator of granulopoiesis: Production of colony-stimulating activity by cultured human endothelial cells10.1182/blood.V56.6.1060.1060 ↗
31. Increased permeability of microcarrier-cultured endothelial monolayers in response to histamine and thrombin. A model for the in vitro study of increased vasopermeability
32. Methods for the initiation and maintenance of human endothelial cell culture10.1177/153857448702100604 ↗
33. Activation of endothelial cells induces platelet thrombus formation on their matrix. Studies of new in vitro thrombosis model with low molecular weight heparin as anticoagulant
34. Differential regulation of stem cell factor mRNA expression in human endothelial cells by bacterial pathogens: An in vitro model of inflammation10.1182/blood.V83.10.2836.2836 ↗
35. An in vitro model of T cell activation by autologous cytomegalovirus (CMV)-infected human adult endothelial cells: Contribution of CMV-enhanced endothelial ICAM-110.4049/jimmunol.160.7.3143 ↗
36. Identification of angiogenic properties of insulin-like growth factor II in in vitro angiogenesis models10.1054/bjoc.1999.0931 ↗
37. In vitro models of vasculogenesis and angiogenesis10.1038/labinvest.3780252 ↗
38. Endothelial von Willebrand factor regulates angiogenesis10.1182/blood-2010-01-264507 ↗
39. Evaluation of the angiogenic potency of a novel exopolysaccharide produced by the MK1 bacterial strain10.1007/s12272-016-0776-y ↗
40. The human endothelial cell in tissue culture10.1007/BF00329383 ↗
41. Human fetal endothelial cells in culture10.1111/j.1600-0609.1975.tb02422.x ↗
42. Endothelial cell culture: Protocol to obtain and cultivate human umbilical endothelial cells10.1016/S0022-1759(01)00408-2 ↗
43. Isolation and culture of human umbilical vein endothelial cells (HUVEC)10.1002/9780471729259.mca04bs4 ↗
44. Characterization of hemodynamic ex vivo model to study endothelial activation by TNF-alpha in prefunded human veins
45. New Cytoplasmic Components in Arterial Endothelia10.1083/jcb.23.1.101 ↗
46. Human endothelial cells in culture10.1679/aohc1950.42.1 ↗
47. Fine structure of vascular endothelium in culture10.1016/S0022-5320(75)90004-0 ↗
48. Ultrastructural identification of umbilical cord vein endothelium in situ and in culture10.1007/BF00223261 ↗
49. Endothelial cells in culture: A model for studying vascular functions10.1006/phrs.1999.0655 ↗
50. Helgason, C.D., and Miller, C.L. (2005). Isolation and culture of primary endothelial cells. Basic Cell Culture Protocols, Springer.10.1385/1592598382 ↗
51. Targeted transplantation of human umbilical cord blood endothelial progenitor cells with immunomagnetic nanoparticles to repair corneal endothelium defect10.1089/scd.2014.0255 ↗
52. Transplantation of cryopreserved human umbilical cord blood-derived endothelial progenitor cells induces recovery of carotid artery injury in nude rats10.1186/s13287-015-0022-4 ↗
53. Niclosamide inhibits the inflammatory and angiogenic activation of human umbilical vein endothelial cells10.1007/s00011-015-0888-8 ↗
54. Urocortin 1 expression and secretion by human umbilical vein endothelial cells: In vitro effects of interleukin 8, interferon gamma, lipopolysaccharide, endothelin 1, prostaglandin F-2alpha, estradiol, progesterone and dexamethasone10.1016/j.peptides.2015.10.010 ↗
55. Resident endothelial progenitor cells from human placenta have greater vasculogenic potential than circulating endothelial progenitor cells from umbilical cord blood10.3727/215517911X617888 ↗
56. Conditioned medium from umbilical cord mesenchymal stem cells induces migration and angiogenesis10.3892/mmr.2015.3409 ↗
57. Temporal studies into attachment, VE-cadherin perturbation, and paracellular migration of human umbilical mesenchymal stem cells across umbilical vein endothelial monolayers10.1089/scd.2014.0207 ↗
58. Gestational diabetes mellitus impairs Nrf2-mediated adaptive antioxidant defenses and redox signaling in fetal endothelial cells in utero10.2337/db13-0169 ↗
59. Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells10.1074/jbc.270.52.31189 ↗
60. Endothelial cells of extremely premature infants display impaired immune response after proinflammatory stimulation10.1038/pr.2017.202 ↗
61. Neutrophil and endothelial adhesive function during human fetal ontogeny10.1189/jlb.0912468 ↗
62. Energy metabolism in umbilical endothelial cells from preterm and term neonates10.1515/jpm.2011.063 ↗
63. P-selectin expression by endothelial cells is decreased in neonatal rats and human premature infants10.1182/blood.V94.2.600 ↗
64. Vascular Endothelial Mitochondrial Function Predicts Death or Pulmonary Outcomes in Preterm Infants10.1164/rccm.201702-0353OC ↗
65. A new, rapid and reproducible method to obtain high quality endothelium in vitro10.1007/s10616-012-9459-9 ↗
66. Tissue-culture evaluation of the viability of blood vessels stored by refrigeration10.1097/00000658-194903000-00006 ↗
67. Culturing endothelial cells of microvascular origin10.1023/A:1009895723488 ↗
68. Human endothelial cells: Use of heparin in cloning and long-term serial cultivation10.1126/science.6635659 ↗
69. Simultaneous isolation of endothelial and smooth muscle cells from human umbilical artery or vein and their growth response to low-density lipoproteins10.1290/1071-2690(2002)038<0265:SIOEAS>2.0.CO;2 ↗
70. Freshney, R.I. (2005). Culture of specific cell types. Culture of Animal Cells: A Manual of Basic Technique, Wiley-Blackwell.10.1002/0471747599.cac023 ↗
71. Human adult endothelial cell growth in culture10.1016/0741-5214(84)90006-5 ↗
72. Serial propagation of human endothelial cells in vitro10.1083/jcb.91.2.420 ↗
73. Model systems for cardiovascular regenerative biology10.1101/cshperspect.a014019 ↗
74. H2S dependent and independent anti-inflammatory activity of zofenoprilat in cells of the vascular wall10.1016/j.phrs.2016.09.017 ↗
75. Endothelium in vitro: A review of human vascular endothelial cell lines for blood vessel-related research10.1023/A:1012259529167 ↗
76. Human umbilical endothelial cells (HUVECs) have a sex: Characterisation of the phenotype of male and female cells10.1186/s13293-014-0018-2 ↗
77. Sex-specific metabolic and functional differences in human umbilical vein endothelial cells from twin pairs10.1016/j.atherosclerosis.2019.10.007 ↗
78. Does cellular sex matter? Dimorphic transcriptional differences between female and male endothelial cells10.1016/j.atherosclerosis.2015.02.018 ↗
79. Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells10.1016/j.bbrc.2017.03.058 ↗
80. A critical analysis of current in vitro and in vivo angiogenesis assays10.1111/j.1365-2613.2008.00633.x ↗
81. Human vascular endothelial cells in culture. Lack of response to serum growth factors10.1016/0014-4827(76)90477-8 ↗
82. Long-term culture of capillary endothelial cells10.1073/pnas.76.10.5217 ↗
83. Induction of human vascular endothelial stress fibres by fluid shear stress10.1038/307648a0 ↗
84. Expression of leukocyte-endothelial cell adhesion molecules on monocyte adhesion to human endothelial cells on plasma treated PET and PTFE in vitro10.1016/S0142-9612(02)00219-3 ↗
85. Identification of endothelial cell genes by combined database mining and microarray analysis10.1152/physiolgenomics.00186.2002 ↗
86. Gestational Diabetes Mellitus Impairs Fetal Endothelial Cell Functions Through a Mechanism Involving MicroRNA-101 and Histone Methyltransferase Enhancer of Zester Homolog-210.1161/ATVBAHA.114.304730 ↗
87. Molecular and cellular properties of PECAM-1 (endoCAM/CD31): A novel vascular cell-cell adhesion molecule10.1083/jcb.114.5.1059 ↗
88. CD36 mediates the In vitro inhibitory effects of thrombospondin-1 on endothelial cells10.1083/jcb.138.3.707 ↗
89. Membrane glycoprotein CD36: A review of its roles in adherence, signal transduction, and transfusion medicine10.1182/blood.V80.5.1105.1105 ↗
90. The human progenitor cell antigen (CD34) is localized on endothelial cells, dermal dendritic cells, and perifollicular cells in formalin-fixed normal skin, and on proliferating endothelial cells and stromal spindle-shaped cells in Kaposi’s sarcoma10.1001/archderm.1991.04510010091009 ↗
91. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues10.1369/jhc.4A6514.2005 ↗
92. The role of junctional adhesion molecules in cell-cell interactions
93. Differentiation of umbilical cord lining membrane-derived mesenchymal stem cells into endothelial-like cells
94. Evidence for involvement of ICAM-1 and VCAM-1 in lymphocyte interaction with endothelium in experimental autoimmune encephalomyelitis in the central nervous system in the SJL/J mouse
95. The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis10.1002/path.1711710311 ↗
96. Polar secretion of endothelin-1 by cultured endothelial cells10.1016/S0021-9258(18)41966-7 ↗
97. The combined role of P- and E-selectins in atherosclerosis10.1172/JCI3001 ↗
98. The P-selectin glycoprotein ligand functions as a common human leukocyte ligand for P-and E-selectins10.1074/jbc.270.19.11662 ↗
99. Development of a high volume screen to identify inhibitors of endothelial cell activation10.1006/abio.1996.0407 ↗
100. Claudin-5 controls intercellular barriers of human dermal microvascular but not human umbilical vein endothelial cells10.1161/ATVBAHA.112.300893 ↗