• Autofluorescence in freshly isolated adult human liver sinusoidal cells 

      Larsen, Anett Kristin; Simon-Santamaria, Jaione; Elvevold, Kjetil; Ericzon, Bo Gøran; Mortensen, Kim Erlend; McCourt, Peter Anthony; Smedsrød, Bård; Sørensen, Karen Kristine (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-13)
      Autofluorescent granules of various sizes were observed in primary human liver endothelial cells (LSECs) upon laser irradiation using a wide range of wavelengths. Autofluorescence was detected in LAMP-1 positive vesicles, suggesting lysosomal location. Confocal imaging of freshly prepared cultures and imaging flow cytometry of non-cultured cells revealed fluorescence in all channels used. Treatment ...
    • Chip-based optical microscopy for imaging membrane sieve plates of liver scavenger cells 

      Helle, Øystein Ivar; Øie, Cristina Ionica; McCourt, Peter Anthony; Ahluwalia, Balpreet Singh (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-08-26)
      The evanescent field on top of optical waveguides is used to image membrane network and sieve-plates of liver endothelial cells. In waveguide excitation, the evanescent field is dominant only near the surface (~100-150 nm) providing a default optical sectioning by illuminating fluorophores in close proximity to the surface and thus benefiting higher signal-to-noise ratio. The sieve plates of liver ...
    • The Computed Sinusoid 

      Boninsegna, Matteo; McCourt, Peter Anthony; Holte, Christopher Florian (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-11-11)
      Hepatic sinusoids are lined with thin endothelial cells with transcellular pores, termed fenestrations. These fenestrations are open channels that connect the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. Fenestrations range from 0.05 to 0.35 µm in diameter and cover 5–15% of the sinusoidal endothelial surface area, depending on their location ...
    • Cost-efficient nanoscopy reveals nanoscale architecture of liver cells and platelets 

      Mao, Hong; Diekmann, Robin; Liang, Hai; Cogger, Victoria Carroll; Le Couteur, David George; Lockwood, Glen P; Hunt, Nick; Schuttpelz, Mark; Huser, Thomas Rolf; Chen, Vivien; McCourt, Peter Anthony (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-09)
      Single-molecule localization microscopy (SMLM) provides a powerful toolkit to specifically resolve intracellular structures on the nanometer scale, even approaching resolution classically reserved for electron microscopy (EM). Although instruments for SMLM are technically simple to implement, researchers tend to stick to commercial microscopes for SMLM implementations. Here we report the construction ...
    • Effect of caffeine and other xanthines on liver sinusoidal endothelial cell ultrastructure 

      Mao, Hong; Szafranska, Karolina; Kruse, Larissa Dorothea; Holte, Christopher Florian; Wolfson, Deanna; Ahluwalia, Balpreet Singh; Whitchurch, Cynthia B.; Cole, Louise; Lockwood, Glen P.; Diekmann, Robin; Le Couteur, David; Cogger, Victoria C.; McCourt, Peter Anthony (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-17)
      Xanthines such as caffeine and theobromine are among the most consumed psychoactive stimulants in the world, either as natural components of cofee, tea and chocolate, or as added ingredients. The present study assessed if xanthines affect liver sinusoidal endothelial cells (LSEC). Cultured primary rat LSEC were challenged with xanthines at concentrations typically obtained from normal consumption of ...
    • The Effects of Metformin on Age-Related Changes in the Liver Sinusoidal Endothelial Cell 

      Hunt, Nicholas J; Lockwood, Glen P; Kang, Sun; Pulpitel, Tamara; Clark, Ximonie; Mao, Hong; McCourt, Peter Anthony; Cooney, Greg; Wali, Jibran; Le Couteur, Frank; Le Couteur, David G; Cogger, Victoria C (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-14)
      Age-related changes in the liver sinusoidal endothelium, particularly the reduction in fenestrations, contribute to insulin resistance in old age. Metformin impacts on the aging process and improves insulin resistance. Therefore, the effects of metformin on the liver sinusoidal endothelium were studied. Metformin increased fenestrations in liver sinusoidal endothelial cells isolated from both young ...
    • The effects of metformin on age-related changes in the liver sinusoidal endothelial cell 

      Hunt, Nick; Lockwood, Glen P; Kang, Sun; Pulpitel, Tamara; Clark, Ximonie; Mao, Hong; McCourt, Peter Anthony; Cooney, Greg; Wali, Jibran; Le Couteur, Frank; Le Couteur, David George; Cogger, Victoria Carroll (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-06-14)
      Age-related changes in the liver sinusoidal endothelium, particularly the reduction in fenestrations, contribute to insulin resistance in old age. Metformin impacts on the aging process and improves insulin resistance. Therefore, the effects of metformin on the liver sinusoidal endothelium were studied. Metformin increased fenestrations in liver sinusoidal endothelial cells isolated from both young ...
    • Efficient uptake of blood-borne BK and JC polyomavirus-like particles in endothelial cells of liver sinusoids and renal vasa recta 

      Simon-Santamaria, Jaione; Rinaldo, Christine Hanssen; Kardas, Piotr; Li, Ruomei; Malovic, Ivana; Elvevold, Kjetil H.; McCourt, Peter Anthony; Smedsrød, Bård; Hirsch, Hans H.; Sørensen, Karen Kristine (Journal article; Tidsskriftartikkel; Peer reviewed, 2014-11-06)
    • From fixed-dried to wet-fixed to live-comparative super-resolution microscopy of liver sinusoidal endothelial cell fenestrations 

      Szafranska, Karolina; Neuman, Tanja; Baster, Zbigniew; Rajfur, Zenon; Szelest, Oskar; Holte, Christopher Florian; Kubisiak, Agata; Kus, Edyta; Wolfson, Deanna; Chlopicki, Stefan; Ahluwalia, Balpreet Singh; Lekka, Malgorzata; Szymonski, Marek; McCourt, Peter Anthony; Zapotoczny, Barlomiej (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-20)
      Fenestrations in liver sinusoidal endothelial cells (LSEC) are transcellular nanopores of 50–350 nm diameter that facilitate bidirectional transport of solutes and macromolecules between the bloodstream and the parenchyma of the liver. Liver diseases, ageing, and various substances such as nicotine or ethanol can negatively influence LSECs fenestrations and lead to defenestration. Over the years, ...
    • Grazing incidence to total internal reflection fluorescence structured illumination microscopy enabled by a prism telescope 

      Ortkrass, Henning; Wiebusch, Gerd; Linnenbrügger, Jochen; Schürstedt, Jasmin; Szafranska, Karolina Joanna; McCourt, Peter Anthony; Huser, Thomas (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-11-13)
      In super-resolution structured illumination microscopy (SR-SIM) the separation between opposing laser spots in the back focal plane of the objective lens affects the pattern periodicity, and, thus, the resulting spatial resolution. Here, we introduce a novel hexagonal prism telescope which allows us to seamlessly change the separation between parallel laser beams for 3 pairs of beams, simultaneously. ...
    • Hepatic disposal of advanced glycation end products during maturation and aging 

      Svistounov, Dmitri; Oteiza, Ana; Zykova, Svetlana; Sørensen, Karen Kristine; McCourt, Peter Anthony; McLachlan, Andrew J; Mccuskey, Robert Scott; Smedsrød, Bård (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
      Aging is characterized by progressive loss of metabolic and biochemical functions and accumulation of metabolic by-products, including advanced glycation end products (AGEs), which are observed in several pathological conditions. A number of waste macromolecules, including AGEs are taken up from the circulation by endocytosis mainly into liver sinusoidal endothelial cells (LSECs) and Kupffer cells ...
    • High-speed TIRF and 2D super-resolution structured illumination microscopy with a large field of view based on fiber optic components 

      Ortkrass, Henning; Schürstedt, Jasmin; Wiebusch, Gerd; Szafranska, Karolina Joanna; McCourt, Peter Anthony; Huser, Thomas Rolf (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-16)
      Super-resolved structured illumination microscopy (SR-SIM) is among the most flexible, fast, and least perturbing fluorescence microscopy techniques capable of surpassing the optical diffraction limit. Current custom-built instruments are easily able to deliver two-fold resolution enhancement at video-rate frame rates, but the cost of the instruments is still relatively high, and the physical size ...
    • Highly oxidized albumin is cleared by liver sinusoidal endothelial cells via the receptors stabilin-1 and -2 

      Holte, Christopher Florian; Szafranska, Karolina Joanna; Kruse, Larissa Dorothea; Simon-Santamaria, Jaione; Li, Ruomei; Svistounov, Dmitri; McCourt, Peter Anthony (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-11-05)
      Oxidized albumin (oxHSA) is elevated in several pathological conditions, such as decompensated cirrhosis, acute on chronic liver failure and liver mediated renal failure. Patient derived oxidized albumin was previously shown to be an infammatory mediator, and in normal serum levels of oxHSA are low. The removal from circulation of oxidized albumins is therefore likely required for maintenance of ...
    • Liver sinusoidal endothelial cells contribute to the uptake and degradation of entero bacterial viruses 

      Øie, Cristina Ionica; Wolfson, Deanna; Yasunori, Tanji; Dumitriu, Gianina; Sørensen, Karen Kristine; McCourt, Peter Anthony; Ahluwalia, Balpreet Singh; Smedsrød, Bård (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-21)
      The liver is constantly exposed to dietary antigens, viruses, and bacterial products with inflammatory potential. For decades cellular uptake of virus has been studied in connection with infection, while the few studies designed to look into clearance mechanisms focused mainly on the role of macrophages. In recent years, attention has been directed towards the liver sinusoidal endothelial cells ...
    • Manipulating fenestrations in young and old liver sinusoidal endothelial cells 

      Hunt, Nicholas J; Lockwood, Glen P; Warren, Alessandra; Mao, Hong; McCourt, Peter Anthony; Le Couteur, David George; Cogger, Victoria Carroll (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-27)
      Fenestrations are pores within liver sinusoidal endothelial cells (LSECs) that enable the transfer of substrates (particularly insulin and lipoproteins) between blood and hepatocytes. With increasing age, there are marked reductions in fenestrations, referred to as pseudocapillarization. Currently, fenestrations are thought to be regulated by vascular endothelial growth factor and nitric oxide (NO) ...
    • Modelling fatty liver disease with mouse liver-derived multicellular spheroids 

      van Os, Elise Anne; Cools, Laura; Eysackers, Nathalie; Szafranska, Karolina; Smout, Ayla; Verhulst, Stefaan; Reynaert, Hendrik; McCourt, Peter Anthony; Mannaerts, Inge; van Grunsven, Leo A. (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-09-28)
      Chronic liver disease can lead to liver fibrosis and ultimately cirrhosis, which is a significant health burden and a major cause of death worldwide. Reliable in vitro models are lacking and thus mono-cultures of cell lines are still used to study liver disease and evaluate candidate anti-fibrotic drugs. We established functional multicellular liver spheroid (MCLS) cultures using primary mouse ...
    • Multimodal on-chip nanoscopy and quantitative phase imaging reveals the nanoscale morphology of liver sinusoidal endothelial cells 

      Butola, Ankit; Coucheron, David Andre; Szafranska, Karolina; Ahmad, Azeem; Mao, Hong; Tinguely, Jean-Claude; McCourt, Peter Anthony; Paramasivam, Senthilkumaran; Mehta, Dalip Singh; Agarwal, Krishna; Ahluwalia, Balpreet Singh (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-11-23)
      Visualization of three-dimensional (3D) morphological changes in the subcellular structures of a biological specimen is a major challenge in life science. Here, we present an integrated chip-based optical nanoscopy combined with quantitative phase microscopy (QPM) to obtain 3D morphology of liver sinusoidal endothelial cells (LSEC). LSEC have unique morphology with small nanopores (50-300 nm in ...
    • Multimodal super-resolution optical microscopy visualizes the close connection between membrane and the cytoskeleton in liver sinusoidal endothelial cell fenestrations 

      Mönkemöller, Viola; Øie, Cristina Ionica; Hubner, Wolfgang; Huser, Thomas Rolf; McCourt, Peter Anthony (Journal article; Tidsskriftartikkel; Peer reviewed, 2015)
      Liver sinusoidal endothelial cells (LSECs) act as a filter between blood and the hepatocytes. LSECs are highly fenestrated cells; they contain transcellular pores with diameters between 50 to 200 nm. The small sizes of the fenestrae have so far prohibited any functional analysis with standard and advanced light microscopy techniques. Only the advent of super-resolution optical fluorescence microscopy ...
    • New ways of looking at very small holes – using optical nanoscopy to visualize liver sinusoidal endothelial cell fenestrations 

      Øie, Cristina Ionica; Mönkemöller, Viola; Hübner, Wolfgang; Schüttpelz, Mark; Mao, Hong; Ahluwalia, Balpreet Singh; Huser, Thomas Rolf; McCourt, Peter Anthony (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-01-10)
      Super-resolution fluorescence microscopy, also known as nanoscopy, has provided us with a glimpse of future impacts on cell biology. Far-field optical nanoscopy allows, for the first time, the study of sub-cellular nanoscale biological structures in living cells, which in the past was limited to electron microscopy (EM) (in fixed/dehydrated) cells or tissues. Nanoscopy has particular utility in the ...
    • Novel targets for delaying aging: The importance of the liver and advances in drug delivery 

      Hunt, Nicholas J; McCourt, Peter Anthony; Le Couteur, David George; Cogger, Victoria C (Journal article; Tidsskriftartikkel, 2018-09-21)
      Age-related changes in liver function have a significant impact on systemic aging and susceptibility to age-related diseases. Nutrient sensing pathways have emerged as important targets for the development of drugs that delay aging and the onset age-related diseases. This supports a central role for the hepatic regulation of metabolism in the association between nutrition and aging. Recently, a role ...