Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression.
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BiBTeXEarly disease diagnosis is key to the effective treatment of diseases. Histopathological analysis of human biopsies is the gold standard to diagnose tissue alterations. However, this approach has low resolution and overlooks 3D (three-dimensional) structural changes resulting from functional alterations. Here, we applied multiphoton imaging, 3D digital reconstructions and computational simulations to generate spatially resolved geometrical and functional models of human liver tissue at different stages of non-alcoholic fatty liver disease (NAFLD). We identified a set of morphometric cellular and tissue parameters correlated with disease progression, and discover profound topological defects in the 3D bile canalicular (BC) network. Personalized biliary fluid dynamic simulations predicted an increased pericentral biliary pressure and micro-cholestasis, consistent with elevated cholestatic biomarkers in patients' sera. Our spatially resolved models of human liver tissue can contribute to high-definition medicine by identifying quantitative multiparametric cellular and tissue signatures to define disease progression and provide new insights into NAFLD pathophysiology.
SEEK ID: https://seek.lisym.org/publications/192
PubMed ID: 31792455
Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM network
Publication type: Not specified
Journal: Nat Med
Citation: Nat Med. 2019 Dec 2. pii: 10.1038/s41591-019-0660-7. doi: 10.1038/s41591-019-0660-7.
Date Published: 2nd Dec 2019
Registered Mode: Not specified
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Created: 4th Dec 2019 at 10:11
Last updated: 8th Mar 2024 at 07:44
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Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM PALs, LiSyM network, LiSyM-Krebs Partnering, Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network
Institutions: Zentrum für Informationsdienste und Hochleistungsrechnen (ZIH), Technische Universität Dresden
https://orcid.org/0000-0003-0137-5106
Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT), LiSyM-Krebs Partnering, Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network
Institutions: Universitätsklinikum Dresden - Medizinische Klinik I, Bereich Gastroenterologie & Hepatologie, Zentrum für Informationsdienste und Hochleistungsrechnen (ZIH), Technische Universität Dresden
Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM network, LiSyM-Krebs Partnering, DEEP-HCC network, Forschungsnetzwerk LiSyM-Krebs
Institutions: Universitätsklinikum Campus Kiel - Klinik für Allgemeine Chirurgie und Thoraxchirurgie, Universitätsmedizin Rostock, Chirurgische Klinik und Poliklinik
Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...
Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)
Web page: https://www.lisym.org/
This comprises the whole LiSyM network
Programme: LiSyM: Liver Systems Medicine
Public web page: http://www.lisym.org
Start date: 1st Jan 2016
One of the tasks of the healthy liver is to store fat. Yet, at some stage, too much fat makes the liver sick. One critical time point occurs when a healthy fatty liver becomes inflamed and progresses to steatohepatitis, or NASH. LiSyM-Pillar I will identify what events lead to this transition. Does it occur in all parts of the liver? Which molecules indicate that it is taking place? Can the degeneration be stopped or undone - and if so, how?
Programme: LiSyM: Liver Systems Medicine
Public web page: http://www.lisym.org/our-work/pillar-research/zones-of-the-liver
Start date: 1st Jan 2016
We apply multiphoton imaging, 3D digital reconstructions and computational simulations to generate spatially-resolved geometrical and functional models of human liver tissue at different stages of non-alcoholic fatty liver disease (NAFLD).
Creator: Fabian Segovia Miranda
Submitter: Fabian Segovia Miranda
Creator: Fabian Segovia Miranda
Submitter: Fabian Segovia Miranda
Morpheus is the modelling and simulation framework for multicellular systems biology developed at Technische Universität Dresden. Manual, examples and binaries for Windows, Linux, MacOS at: https://morpheus.gitlab.io Open source code at: https://gitlab.com/morpheus.lab/morpheus
Creators: Lutz Brusch, Jörn Starruß, Walter de Back, Andreas Deutsch
Submitter: Lutz Brusch
Model type: Agent based modelling
Model format: MorpheusML
Environment: Morpheus
Code for the bile flow model in Segovia-Miranda et al.: Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression (https://www.nature.com/articles/s41591-019-0660-7)
See the README file in the link for details installing and running the code.
Creators: Michael Kücken, Lutz Brusch
Submitter: Michael Kücken
Model type: Ordinary differential equations (ODE)
Model format: Not specified
Environment: Not specified
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