Z Gastroenterol 2025; 63(01): e12-e13
DOI: 10.1055/s-0044-1801022
Abstracts │ GASL
Poster Visit Session I
BASIC HEPATOLOGY (FIBROGENESIS, NPC) 14/02/2025, 12.30pm – 01.00pm

Cellular cytokinesis, hyperplasia and hypertrophy define critical phases for liver regeneration efficiency

Stella Seddik Hammad
1   Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
Amnah Othman
2   Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo)
,
Mohamed Albadry
3   University Clinic Jena, Jena
,
Zhipeng Deng
4   University of Leipzig
,
Achim Weber
5   University Hospital Zurich
,
Anne Dropmann
1   Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
Adrian Friebel
4   University of Leipzig
,
Jan Hengstler
2   Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo)
,
Stefan Hoehme
4   University of Leipzig
,
Ursula Klingmüller
6   German Cancer Research Center (DKFZ)
,
Matthias Ebert
7   University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University
,
Kai Breuhahn
8   University Hospital Heidelberg
,
Beat Muellhaupt
9   University Hospital Zurich, University of Zurich
,
Steven Dooley
1   Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
Uta Dahmen
3   University Clinic Jena, Jena
,
Seddik Hammad
1   Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
› Author Affiliations
 
 

    Adult liver consists of hepatocytes with multiple ploidy classes. Quantifying ploidy and nuclearity distributions aids in developing models predicting regeneration efficiency after surgery.

    Mice were subjected to 2/3 partial hepatectomy (PHx) and observed between 0.5 to 90 days. 3D reconstructed images were generated from liver tissue slices co-stained with antibodies to visualize sinusoidal networks, pericentral hepatocytes, S-phase, and cell nuclei. The 3D quantification of polyploidy, nuclearity and proliferation using TiQuant was mathematically modeled using a state-transition framework integrated into a 3D spatiotemporal liver regeneration model.

    In healthy murine liver, more than 85% of hepatocytes display nuclear polyploidy, with about 75% being binucleated. Following PHx, about 50% of binucleated hepatocytes are lost within 24 hours, indicating cytokinesis occurs without altering DNA content. From postoperative days 2 to 7, fewer nuclei per cell and increased DNA content suggest that DNA synthesis followed by cytokinesis is the primary regeneration mechanism. In later stages of regeneration, an increase in liver mass indicates that hypertrophy appears to be the predominant process. Mathematical models suggest that cytokinesis regulate the transition between mono- and binucleated cells during regeneration.

    In conclusion, the process of liver regeneration can be divided in three phases: Cyokinesis without DNA synthesis, DNA synthesis followed by cytokinesis and hypertrophy to foster mass recovery. The percentage of binucleated hepatocytes is a predictor of the initial regeneration efficacy based on cytokinesis. This mechanism can be modeled using a state-transition framework integrated into a 3D spatio-temporal liver regeneration model, which simulates tissue-scale regenerative capacity.


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    Publication History

    Article published online:
    20 January 2025

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