Key Applications for Endothelial Cells

Endothelium with red blood cells

White Papers - Vascular Research

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  • Selected Applications

    Lonza offers endothelial cells from normal and diabetic donors. Read how researchers have been using our cells to study diabetes. We also carry a wide variety of HUVECs for angiogenesis assays.

     

    Select the application of interest from the navigation above or register to download our white papers below.

     

       

    White Papers – Vascular Research

    Diabetes-related Differential Gene Expression in Primary Human Adipose-derived Stem Cells and Aortic Endothelial Cells

     

    With the prevalence of diabetes growing worldwide, the availability of primary human cells from diabetic donors is critical to increase research and knowledge about the disease at a cellular level. In this study, we sought to identify genes differentially regulated in diabetic type 1 and type 2 adipose-derived stem cells (ADSCs) and human aortic endothelial cells (HAECs).

     

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    More White Papers Available

    • Automated Cell Signaling Assays Using Primary Human Umbilical Vein Endothelial Cells
    • Tube Formation Assay with Primary Human Umbilical Vein Endothelial Cells
    •  Expanded HUVECs for High-Throughput Screening
    • And more                               

     

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    What Are Endothelial Cells?

    Explore what endothelial cells are, where they occur in the body and what functions they have.

    Learn more
     
  • Blood Brain Barrier Models

    The endothelium acts as a barrier between blood and rest of the body tissue. It is selectively permeable for certain chemicals and white blood cells to move across from blood to tissue or for waste and carbon-dioxide to move from tissue to blood.

    The blood-brain barrier (BBB) is formed by microvascular endothelial cells, pericytes and astrocytes. It prevents the entry of most large hydrophilic molecules and many potentially harmful toxins from the blood into the brain. On the other hand, it also prevents the entry of many therapeutic agents into the brain making it difficult to develop drugs that can efficiently cross the blood-brain-barrier. Considerable efforts are made to better mimic and understand the functions of blood brain barrier systems to increase the efficacy of drug development.    

    Blood vessels in the brain 

    A schematic sketch of blood vessels in the brain

    By Armin Kübelbeck, CC BY 3.0

     

     

    Human brain microvascular endothelial cells 

    Spampinato et al. studied the effects of bioactive lipid S1P and fingolimod (an immune drug) on the BBB models. In this figure, human brain microvascular endothelial cells were cultured in EGM™-2 SingleQuot Kits and immunostained for the cytoskeleton component F-actin. Fig a. shows a confluent monolayer characterized by fusiform morphology and strict cell-to-cell contacts. Fig b shows exposure to inflammatory cytokines, TNFα and IFNγ, causing changes in hBMVEC morphology as consequence of reduced cell viability. In the presence of S1P (Fig c) or fingolimod phosphate (Fig d), effects of inflammatory cytokines on hBMVEC morphology are lessened. (CC BY 4.0)

      

    Select References with Lonza’s EGM™-2 Endothelial Growth Medium for Developing Blood-Brain-Barrier Models with Brain Microvascular Endothelial Cells

    • HCMEC/D3 cell line is commonly used as an vitro model to develop the BBB models. Vu et al demonstrates how HCMEC/D3 cell line can be grown in rich endothelial growth medium EGM™-2 on a collagen-coated porous membrane. The researchers were studying whether C. neoformans can cross the brain endothelium transcellularly without causing significant damage to the endothelial cells. .
    • Human Brain MicroVascular Endothelial Cells (hBMVEC), were grown in MCDB-131 media supplemented with EGM™-2 SingleQuots. Spampinatoet al. examined the ability of S1P(a bioactive sphigolipid) and fingolimod (an immune modulatory drug) to act on the BBB.

       

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  • Angiogenesis

    Angiogenesis is a term used to refer to “formation of new blood vessels”. Endothelial cells play a key function in maintaining homeostasis and formation of new blood vessels. “Angiogenesis involves the migration, growth, and differentiation of endothelial cells, which line the inside wall of blood vessels.”           


    Angiogenesis has been found to have key applications in cancer research. Tumor is supported by formation of new blood vessels that provides oxygen nutrients for cancer cells to grow and invade other tissue. Current research is focused on understanding how natural and/or synthetic angiogenesis inhibitors, also known as antiangiogenic agents, can have implications on stopping or lessening tumor growth. The key role of angiogenesis in tumor development and cancer metastasis makes inhibition of angiogenesis an attractive strategy to target a number of cancer types (Timar et. al., 2001).


    Human umbilical vein endothelial cells (HUVEC) are commonly used endothelial cell types for studying angiogenesis in vitro. VEGF (or VEGF-A “vascular endothelial growth factor”) and VEGFR-2 are key cytokines involved in stimulating angiogenesis. One of the easiest screening and target validation strategies for anti-angiogenic target identification involves knocking down targets in HUVECs and assessing subsequent effects on tube formation. The usage of small interfering RNA (siRNA) is one of the strategies to knock-down RNA, and thereby protein expression within cells. siRNA can be delivered within cells using either chemical transfection or electroporation-based strategies such as the one offered by the Lonza Nucleofector™ Technology.

     

    White Papers

    • Automated Cell Signaling Assays Using Primary Human Umbilical Vein Endothelial Cells
    • Tube Formation Assay with Primary Human Umbilical Vein Endothelial Cells
    • Expanded HUVECs for High-Throughput Screening
    • Assessment of the Anti-Angiogenic Effect of VEGFR2 siRNA in HUVEC

     

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    Endothelial Cells - HUVECs red blue stain

    Human Umbilical Vein Endothelial Cells (HUVEC) with red/blue stain

         
         
    Select References with Lonza’s HUVEC and EGM™-2 Medium for Angiogenesis Assays           
    • Legeay et al, in their study, show Lonza’s HUVECs were cultured in EGM-2 Medium and exposed to DEET found in mosquito repellants. The team showed how DEET specifically stimulates endothelial cells that promote angiogenesis which increases tumor growth.
    • Wang et al demonstrates Cetuximab inhibits tumor angiogenesis in vitro. Pooled HUVECs from Lonza were cultured in EGM-2 medium and migration assay was studied in the presence of pretreated medium with Cetuximab and Cal27 cells.   

     

    endothelial-cells-in-vitro-migration-assay-with-Lonza’s-pooled-huvecs                                         

    Wang et al demonstrates Cetuximab inhibits tumor angiogenesis in vitro. The research group performed an in vitro migration assay with Lonza’s pooled HUVECs to further confirm the function of cetuximab in angiogenesis in vitro. As shown in Fig. B, the findings exhibited that conditional medium (CM) significantly decreased HUVEC migration and tube formation after cetuximab pretreatment under both normoxic and hypoxic conditions when compared with the negative vehicle. (CC0 1.0)

       

     

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    References

    1 https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet                        

  • Tissue Engineering

    The first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago. With cardiovascular diseases becoming more prevalent and the need the limited availability of healthy autologous vessels for bypass grafting procedures, there is an increased need to look for alternative sources to increase treatment efficiency. This has fueled the growth of in vitro vascular tissue engineering field as driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel.”1

    Advancements are being made in vitro for testing new methods for vascular graft engineering ranging from seeding cells into decellularized naturally-derived scaffolds to using synthetic scaffolds and testing cell adherence. For such investigations, mimicking in vivo conditions as closely as possible becomes vital and hence primary cultures of endothelial and smooth muscle cells are utilized as ideal cell sources to advance research in this arena.                    

      

    Histological examination of the luminal side of the vascular graft

    Histological examination of the luminal side of the vascular graft

    At pre-implantation, the vascular endothelial cells distribute to the entire area of the graft (data not shown). Conversely, after implantation, vWF, CD31 and CellTracker Red-positive endothelial cells are seen at the inner lumen of the vessel. Furthermore, the vascular endothelial cells cover the inner surface of the vessel more continuously on the fifth day than on the second.

    Itoh, et al developed a novel method to create scaffold-free tubular tissue from multicellular spheroids (MCS) using a “Bio-3D printer”-based system. The research team made scaffold-free tubular tissues from MCSs composed of Lonza’s human umbilical vein endothelial cells, human aortic smooth muscle cells, and normal human dermal fibroblasts. The tubular tissues were cultured in a perfusion system and implanted into the abdominal aortas of F344 nude rats. The scaffold-free tubular tissues made of MCS using a Bio-3D printer underwent remodeling and endothelialization. (CC BY 4.0)

      

    Select References with Lonza’s Endothelial and Cardiac Smooth Muscle Cells for Tissue Engineering Applications

    • Bastijanic et. al utilized Lonza’s Human pulmonary artery endothelial cells (HPAECs) and human coronary artery smooth muscle cells (HCASMCs) and cultured them to 80–90% confluency in endothelial cell growth medium (EGM) or smooth muscle cell growth medium (SmGM), respectively. The cells were integrated individually within synthetic vascular scaffolds to test for cell adherence showing promising results.
    • Melchiorri et. al utilized Lonza’s HUVECs with biodegradable vascular grafts in an effort to improve the vascular graft endothelialization using enhancement techniques to the scaffold.    

       

     

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    References

    1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384697/

  • Inflammatory Processes

    Inflammation is body’s natural process of removing harmful stimuli and begin the healing process. Endothelial cells have been found to function as key modulators of the inflammatory processes. Consequently, dysfunction in endothelial cells can result in implications to inflammatory processes as well. Inflammation has also been linked to many disease areas including cardiovascular, pulmonary, neurological, autoimmune, diabetes to name a few. Therefore, endothelial cells become crucial components supporting research in many disease areas.


    According to an article by NatureReviews, microvascular endothelial cells (HMVEC) regulate and are active participants in inflammatory processes at a site of inflammation. The properties of endothelial cells change from acute to chronic inflammation and from innate to adaptive immunity. The article concludes that since inflammatory processes and endothelial cells are correlated, many anti-inflammatory therapies influence the behavior of endothelial cells and vascular therapeutics influence inflammation.

      

     

    Effects of nitric oxide on the vascular endothelium, inflammatory cells, and platelets.

    Sickle Cell Disease – Current Treatment and New Therapeutical Approaches

    Effects of nitric oxide on the vascular endothelium, inflammatory cells, and platelets. The image shows effects of NO impacting inflammatory cells and endothelial cells.

                           

     

                           


    Select References with Lonza’s Endothelial Cells as Regulators of Inflammatory Processes

    • Tellier, et al. stated that numerous studies have evidenced different consequences of cycling hypoxia versus chronic hypoxia on cancer cells as well as on endothelial cell behavior, altering angiogenesis, tumor growth, and metastasis. Endothelial cells, key regulators of tumor growth, differentially respond to changes in tumor microenvironment. The team hypothesized that endothelial cells could be a perceptive sensor of cycling hypoxia and inflammation simultaneously. Lonza’s HUVEC and EGM growth medium were used with colon cancer tissue to perform the study. Results showed that endothelial cells exposed to cycling hypoxia displayed an amplified inflammatory phenotype.
    • Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions. Dong, et al. sought to better understand the molecular mechanism of how cells respond to acidic tissue microenvironment. The team was investigating GPR4, a protein expressed by endothelial cells and also activated under acidic conditions. Several endothelial cell types from Lonza including  human umbilical vein endothelial cells (HUVEC), human lung microvascular endothelial cells (HMVEC-L) and human pulmonary artery endothelial cells (HPAEC) were utilized and grown in endothelial cell growth medium 2 (EGM-2), or EGM-2-MV medium. 

      

     


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  • Diabetes and Cardiovascular Diseases

    Endothelial dysfunction causes an imbalance between vasodilation and vasoconstriction. The term, endothelial dysfunction, has been used to refer to altered anticoagulant and anti-inflammatory properties of the endothelium, impaired modulation of vascular growth, and dysregulation of vascular remodeling1. Endothelial dysfunction is tied to an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide (NO) bioactivity in the vessel wall. This endothelial dysfunction has been implicated in many vascular diseases such as atherosclerosis, diabetes, hypertension and more. Impaired endothelium function in the coronary circulation has been found to have prognostic implications in that it predicts adverse cardiovascular events and long-term outcome1.
     

    White Paper

    • Diabetes-related Differential Gene Expression in Primary Human Adipose-derived Stem Cells and Aortic Endothelial Cells         


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    “Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium and accelerate atherosclerosis. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease”.2              


    Understanding and treating endothelial dysfunction is a major focus in the prevention of vascular complications caused due to diabetes. Comparing the function of endothelial cells from normal and diabetic donors becomes crucial to better understand the deficiencies in endothelial cells from diabetic donors. Lonza’s broad offering of human endothelial cells from normal and diabetic type 1 and 2 donors is better suited to support such studies.

         
         
    Select References with Lonza’s Endothelial Cells from Normal and Diabetic Donors  
    • Down-regulation of miR-200b increases VEGF, mediating structural and functional changes in the retina in diabetes. Ruiz,et al. were trying to establish a relationship between PRC2 (Polycomb Repressive Complex 2) and microRNA miR-200b to understand the mechanisms regulating miR-200b in diabetes. Lonza’s human dermal microvascular endothelial cells (HDMECs) isolated from non-diabetic and type 1 and type 2 diabetic individuals were utilized and grown in Lonza’s Endothelial Medium.
    • Tsukahara, et al. were trying to understand the mechanism of the cPA-PPARγ axis in the coronary artery endothelium, especially in patients with type II diabetes. Lonza’s human coronary artery endothelial cells (HCAECs) from normal and type 2 diabetic donors were grown in Lonza’s EGM™-2 Growth Medium to support the study.  

     

      

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    References

    1 http://circres.ahajournals.org/content/87/10/840

    2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350146/