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Published year: 20192
Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression.

Abstract (Expand)

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.

Authors: F. Segovia-Miranda, H. Morales-Navarrete, M. Kucken, V. Moser, S. Seifert, U. Repnik, F. Rost, M. Brosch, A. Hendricks, S. Hinz, C. Rocken, D. Lutjohann, Y. Kalaidzidis, C. Schafmayer, L. Brusch, J. Hampe, M. Zerial

Date Published: 2nd Dec 2019

Publication Type: Not specified

Liquid-crystal organization of liver tissue.

Abstract (Expand)

Functional tissue architecture originates by self-assembly of distinct cell types, following tissue-specific rules of cell-cell interactions. In the liver, a structural model of the lobule was pioneered … by Elias in 1949. This model, however, is in contrast with the apparent random 3D arrangement of hepatocytes. Since then, no significant progress has been made to derive the organizing principles of liver tissue. To solve this outstanding problem, we computationally reconstructed 3D tissue geometry from microscopy images of mouse liver tissue and analyzed it applying soft-condensed-matter-physics concepts. Surprisingly, analysis of the spatial organization of cell polarity revealed that hepatocytes are not randomly oriented but follow a long-range liquid-crystal order. This does not depend exclusively on hepatocytes receiving instructive signals by endothelial cells, since silencing Integrin-beta1 disrupted both liquid-crystal order and organization of the sinusoidal network. Our results suggest that bi-directional communication between hepatocytes and sinusoids underlies the self-organization of liver tissue.

Authors: H. Morales-Navarrete, H. Nonaka, A. Scholich, F. Segovia-Miranda, W. de Back, K. Meyer, R. L. Bogorad, V. Koteliansky, L. Brusch, Y. Kalaidzidis, F. Julicher, B. M. Friedrich, M. Zerial

Date Published: 17th Jun 2019

Publication Type: Not specified

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