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Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression
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Abstract
Early 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.
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“Interestingly, BA toxicity as result of impaired hepatobiliary excretory function18 19 and functional (micro)cholestasis20 may also be involved in the pathogenesis of NASH.12”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [20]
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Metadata
- Authors
- Segovia-Miranda, F., Morales-Navarrete, H., Kücken, M., Moser, V., Seifert, S., Repnik, U., Rost, F., Brosch, M., Hendricks, A., Hinz, S., Röcken, C., Lütjohann, D., Kalaidzidis, Y., Schafmayer, C., Brusch, L., Hampe, J., & Zerial, M.
- Affiliations
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Center for Information Services and High Performance Computing (DE)
- University Hospital Carl Gustav Carus (DE)
- Max Planck Institute for the Physics of Complex Systems (DE)
- Universitätsmedizin Rostock (DE)
- University Hospital Schleswig-Holstein (DE)
- University Hospital Bonn (DE)
- Lomonosov Moscow State University (RU)
- Corresponding author
- Hampe, Jochen
- Zerial, Marino
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-12
- Volume
- 25
- Issue
- 12
- Pages
- 1885-1893
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6899159
- OpenAlex
- W2990404188
- Cited by
- 109
- References
- 107
- Citations by year
- 2026: 20 · 2025: 21 · 2024: 11 · 2023: 9 · 2022: 15 · 2021: 22 · 2020: 8 · 2019: 2
- FWCI
- 8.94
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-15-CMED-0002)
- Bundesministerium für Bildung und Forschung (031L008A, 031L0044, 031L0038, 031L0031, 031L0033)
- Technische Universität Dresden
- Max-Planck-Gesellschaft
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- non-alcoholic fatty liver disease, biliary pressure, morphometrics, disease progression, liver histopathology
- MeSH terms
- Bile Canaliculi, Biliary Tract, Cholestasis, Computer Simulation, Humans, Liver, Models, Biological, Disease Progression, Imaging, Three-Dimensional, Early Diagnosis, Non-alcoholic Fatty Liver Disease
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