English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

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

MPS-Authors
/cone/persons/resource/persons222343

Segovia-Miranda,  Fabián
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/cone/persons/resource/persons219465

Morales-Navarrete,  Hernán
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/cone/persons/resource/persons219662

Seifert,  Sarah
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/cone/persons/resource/persons219285

Kalaidzidis,  Yannis
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/cone/persons/resource/persons219807

Zerial,  Marino
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Segovia-Miranda, F., Morales-Navarrete, H., Kücken, M., Moser, V., Seifert, S., Repnik, U., et al. (2019). Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression. Nature medicine, 25(12), 1885-1893. doi:10.1038/s41591-019-0660-7.


Cite as: https://hdl.handle.net/21.11116/0000-0006-7E66-B
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.