A liver digital twin for in silico testing of cellular and inter-cellular mechanisms in regeneration after drug-induced damage.

Abstract:

This communication presents a mathematical mechanism-based model of the regenerating liver after drug-induced pericentral lobule damage resolving tissue microarchitecture. The consequence of alternative hypotheses about the interplay of different cell types on regeneration was simulated. Regeneration dynamics has been quantified by the size of the damage-induced dead cell area, the hepatocyte density and the spatial-temporal profile of the different cell types. We use deviations of observed trajectories from the simulated system to identify branching points, at which the systems behavior cannot be explained by the underlying set of hypotheses anymore. Our procedure reflects a successful strategy for generating a fully digital liver twin that, among others, permits to test perturbations from the molecular up to the tissue scale. The model simulations are complementing current knowledge on liver regeneration by identifying gaps in mechanistic relationships and guiding the system toward the most informative (lacking) parameters that can be experimentally addressed.

SEEK ID: https://seek.lisym.org/publications/440

PubMed ID: 38371522

Projects: C-TIP-HCC network, LiSyM network

Publication type: Journal

Journal: iScience

Citation: iScience. 2023 Sep 28;27(2):108077. doi: 10.1016/j.isci.2023.108077. eCollection 2024 Feb 16.

Date Published: 16th Feb 2024

Registered Mode: by PubMed ID

Authors: J. Zhao, A. Ghallab, R. Hassan, S. Dooley, J. G. Hengstler, D. Drasdo

help Submitter
Activity

Views: 223

Created: 30th Sep 2024 at 08:32

help Tags

This item has not yet been tagged.

help Attributions

None

Powered by
(v.1.15.2)
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH