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Nat Med. 2019 Dec;25(12):1885-1893. doi: 10.1038/s41591-019-0660-7. Epub 2019 Dec 2.

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

Author information

1
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
2
Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.
3
Department of Medicine I, Gastroenterology and Hepatology, University Hospital Carl-Gustav-Carus, Technische Universität Dresden (TU Dresden), Dresden, Germany.
4
Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
5
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden, Germany.
6
Department of General Surgery, University Hospital Rostock, Rostock, Germany.
7
University Hospital Schleswig-Holstein, Kiel, Germany.
8
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
9
Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia.
10
Department of Medicine I, Gastroenterology and Hepatology, University Hospital Carl-Gustav-Carus, Technische Universität Dresden (TU Dresden), Dresden, Germany. jochen.hampe@uniklinikum-dresden.de.
11
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden, Germany. jochen.hampe@uniklinikum-dresden.de.
12
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. zerial@mpi-cbg.de.

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.

PMID:
31792455
PMCID:
PMC6899159
[Available on 2020-06-02]
DOI:
10.1038/s41591-019-0660-7

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