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3D reconstruction of human liver tissue at cellular resolution
Wesley B Fabyan1,2, Chelsea L Fortin1,2,3, Dorice L Goune1,2
1Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Science Advances
|February 18, 2026
Summary
Three-dimensional reconstructions reveal liver cirrhosis disrupts normal liver architecture, causing sinusoid dysregulation and network fragmentation. This 3D analysis offers new insights into cirrhotic pathobiology and potential treatments.
Area of Science:
- Hepatology
- Pathology
- Medical Imaging
Background:
- Liver microstructure is crucial for function; architectural disruption is pathologic.
- Two-dimensional (2D) histopathology has limitations in capturing complex 3D liver structures.
- Understanding 3D liver architecture is vital for diagnosing and treating liver diseases.
Purpose of the Study:
- To create detailed 3D reconstructions of nonfibrotic and cirrhotic human liver tissue.
- To analyze architectural changes in cirrhotic livers using advanced imaging techniques.
- To identify specific structural alterations associated with liver cirrhosis.
Main Methods:
- Immunostaining and tissue clearing techniques were employed.
- Advanced microscopy and computational software were used for 3D reconstruction.
- Multilobular reconstructions of human liver tissue (nonfibrotic and cirrhotic) were generated.
Main Results:
- Cirrhotic livers showed sinusoid zonal dysregulation.
- A reduction in glutamine synthetase-expressing pericentral hepatocytes was observed.
- Regression of central vein and hepatic arterial networks, along with biliary network fragmentation, was identified, suggesting a pro-portalization phenotype.
Conclusions:
- Three-dimensional (3D) pathological analysis reveals significant architectural disruption in cirrhotic human livers.
- The observed changes indicate a pro-portalization/decentralization phenotype in cirrhotic tissue.
- Further implementation of 3D pathological analyses can deepen the understanding of cirrhotic pathobiology and guide novel therapeutic strategies.
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