Hydrodynamics of bile flow

Jansen, Petér L. M.

doi:10.1002/hep.29618

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…Bile flow is essential for normal liver function. Bile accumulation, due to its detergent-like properties, can cause liver damage 49,50 and bile pressure can affect metabolism 51 . Indeed, the accumulation of LD 52 and BAs 53 could induce oxidative stress and trigger apoptosis 29 , which is consistent with the reduction in pericentral hepatocytes observed in STEA and eNASH.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression

Segovia-Miranda

Morales‐Navarrete

Kücken

et al. 2019

Nat Med

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Section: Discussionmentioning

confidence: 99%

Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression

Segovia-Miranda

Morales‐Navarrete

Kücken

et al. 2019

Nat Med

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“…Unimpaired bile flow is essential for normal liver function. Previous studies have documented that bile accumulation, due to its detergent-like properties, can cause liver damage 52,53 and bile pressure can affect metabolism 54 . The occurrence of zonated cholestasis is a new piece in the NAFLD physiopathology puzzle that contributes to clarify some aspects of the disease so far without explanation, e.g.…”

Section: Discussionmentioning

confidence: 99%

3D spatially-resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression

Segovia-Miranda

Morales‐Navarrete

Kücken

et al. 2019

Preprint

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25Early disease diagnosis is key for the effective treatment of diseases. It relies on the 26 identification of biomarkers and morphological inspection of organs and tissues. 27Histopathological analysis of human biopsies is the gold standard to diagnose tissue 28 alterations. However, this approach has low resolution and overlooks 3D structural changes 29 that are consequence of functional alterations. Here, we applied multiphoton imaging, 3D 30 digital reconstructions and computational simulations to generate spatially-resolved 31 geometrical and functional models of human liver tissue at different stages of non-alcoholic 32 fatty liver disease (NAFLD). We identified a set of new morphometric cellular parameters 33 correlated with disease progression. Moreover, we found profound topological defects in the 34 3D bile canaliculi (BC) network. Personalized biliary fluid dynamic simulations predicted an 35 increased pericentral biliary pressure and zonated cholestasis, consistent with elevated 36 cholestatic biomarkers in patients' sera. Our spatially-resolved models of human liver tissue 37 can contribute to high-definition medicine by identifying quantitative multi-parametric cellular 38 and tissue signatures to define disease progression and provide new insights into NAFLD 39 pathophysiology. 42High definition medicine is emerging as an integrated approach to profile and restore 43 the health of an individual using a pipeline of multi-parametric analytical and therapeutic 44 technologies 1 . High-definition medicine relies on large data sets, e.g. genomics, 45 metabolomics, to characterize human health at the molecular level. It also relies on imaging, 46 image analysis and computational modelling approaches to identify structural and functional 47 abnormalities in organs and tissues associated with a disease state. Histology has been 48 classically used to characterize tissue structure and remains the method of choice to 49 describe and monitor a large variety of pathologies 2 . However, this technique has several 50 disadvantages, e.g. it is subjective (depends on the pathologist's skills), is often semi-51 quantitative and provides only two-dimensional (2D) information, i.e. does not account for 52 the three-dimensional (3D) complexity of tissues 3 . In recent years, an increasing number of 53 studies have highlighted the importance of considering 3D information for the 54 histopathological examination of tissues 4-7 . This is particularly crucial for the analysis of 3D 55 structures. The liver is a pertinent example of an organ with a complex 3D tissue 56 organization 8 . It consists of functional units, the liver lobule 9,10 , containing two intertwined 57 networks, the sinusoids for blood flow and the bile canaliculi (BC) for bile secretion and flux 9 . 58 Sinusoids and BC run antiparallel along the central vein (CV)-portal vein (PV) axis. The 59 hepatocytes are the major parenchymal cells and display a peculiar and unique type of cell 60 polarity distinct from that of simple epithelia 11 . Whereas in epit...

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“…Increased shear stress within the sinusoids can negatively impact the LSECs, leading to the enlargement of fenestrae through fusion and resultant disturbed microcirculation between the sinusoidal and perisinusoidal space. HCs secrete bile, which is transported via canaliculi, which are about 1.4 µm wide and eventually drain into the portal tracts' bile ductules, presumably resulting in very low shear stress [103]. Various disease states can increase the viscosity of bile, resulting in elevated shear stress.…”

Section: Physical Stresses and Fluid Flowmentioning

confidence: 99%

Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

et al. 2021

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Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies critical parameters for organization and function (tissue organization, blood flow, and physical stresses), reviews current microfluidic approaches to recreate tissues, and discusses current shortcomings and future directions for the development and application of these technologies. The organs emphasized are those involved in the metabolism or excretion of drugs (hepatic and renal systems) and organs sensitive to drug toxicity (cardiovascular system). This article examines the microfluidic/microfabrication approaches for each organ individually and identifies specific examples of TCs. This review will provide an excellent starting point for understanding, designing, and constructing novel TCs for possible integration within MPS.

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Hydrodynamics of bile flow

Cited by 3 publications

References 7 publications

Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression

Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression

3D spatially-resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression

Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

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