title: Morphology and vasoactive hormone profiles from endothelial cells derived from stem cells of different sources.
abstract: Endothelial cells form a highly specialised lining of all blood vessels where they provide an anti-thrombotic surface on the luminal side and protect the underlying vascular smooth muscle on the abluminal side. Specialised functions of endothelial cells include their unique ability to release vasoactive hormones and to morphologically adapt to complex shear stress. Stem cell derived-endothelial cells have a growing number of applications and will be critical in any organ regeneration programme. Generally endothelial cells are identified in stem cell studies by well-recognised markers such as CD31. However, the ability of stem cell-derived endothelial cells to release vasoactive hormones and align with shear stress has not been studied extensively. With this in mind, we have compared directly the ability of endothelial cells derived from a range of stem cell sources, including embryonic stem cells (hESC-EC) and adult progenitors in blood (blood out growth endothelial cells, BOEC) with those cultured from mature vessels, to release the vasoconstrictor peptide endothelin (ET)-1, the cardioprotective hormone prostacyclin, and to respond morphologically to conditions of complex shear stress. All endothelial cell types, except hESC-EC, released high and comparable levels of ET-1 and prostacyclin. Under static culture conditions all endothelial cell types, except for hESC-EC, had the typical cobblestone morphology whilst hESC-EC had an elongated phenotype. When cells were grown under shear stress endothelial cells from vessels (human aorta) or BOEC elongated and aligned in the direction of shear. By contrast hESC-EC did not align in the direction of shear stress. These observations show key differences in endothelial cells derived from embryonic stem cells versus those from blood progenitor cells, and that BOEC are more similar than hESC-EC to endothelial cells from vessels. This may be advantageous in some settings particularly where an in vitro test bed is required. However, for other applications, because of low ET-1 release hESC-EC may prove to be protected from vascular inflammation.
authors.affiliation: Dept. of Cardiothoracic Pharmacology, Vascular Biology Section, National Heart and Lung Institute, Imperial College London, SW3 6LY, United Kingdom. Electronic address: daniel.reed09@imperial.ac.uk.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Reed
authors.affiliation: Dept. of Cardiac Pharmacology, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Imperial College London, W12 0NN, United Kingdom.
authors.forename: Gabor
authors.initials: G
authors.lastname: Foldes
authors.affiliation: Dept. of Cardiothoracic Pharmacology, Vascular Biology Section, National Heart and Lung Institute, Imperial College London, SW3 6LY, United Kingdom.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Kirkby
authors.affiliation: Dept. of Cardiothoracic Pharmacology, Vascular Biology Section, National Heart and Lung Institute, Imperial College London, SW3 6LY, United Kingdom.
authors.forename: Blerina
authors.initials: B
authors.lastname: Ahmetaj-Shala
authors.affiliation: Dept. of Cardiothoracic Pharmacology, Vascular Biology Section, National Heart and Lung Institute, Imperial College London, SW3 6LY, United Kingdom.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mataragka
authors.affiliation: Dept. of Cardiothoracic Pharmacology, Vascular Biology Section, National Heart and Lung Institute, Imperial College London, SW3 6LY, United Kingdom; Qatar Foundation Research and Development Division, Doha, Qatar.
authors.forename: Nura A
authors.initials: NA
authors.lastname: Mohamed
authors.affiliation: Dept. of Cardiothoracic Pharmacology, Vascular Biology Section, National Heart and Lung Institute, Imperial College London, SW3 6LY, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Francis
authors.affiliation: Heart and Vascular Center, Semmelweis University, Budapest H1122, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Gara
authors.affiliation: Dept. of Cardiac Pharmacology, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Imperial College London, W12 0NN, United Kingdom.
authors.forename: Sian E
authors.initials: SE
authors.lastname: Harding
authors.affiliation: Dept. of Cardiothoracic Pharmacology, Vascular Biology Section, National Heart and Lung Institute, Imperial College London, SW3 6LY, United Kingdom.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Mitchell
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology*; D019332:Endothelin-1 / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D033081:Shear Strength; D013234:Stem Cells / Q000166:cytology*; D013314:Stress, Mechanical; D014662:Vasoconstrictor Agents / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D019332:Endothelin-1; D006728:Hormones; D016209:Interleukin-8; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014662:Vasoconstrictor Agents; D011464:Epoprostenol
keywords: Endothelial cells; Endothelin-1; Prostacyclin; Shear stress; Stem cells