ArticleFrontiers in bioengineering and biotechnology2014
A Multiscale Agent-Based in silico Model of Liver Fibrosis Progression.
Article in Frontiers in bioengineering and biotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Application of Magnetic Resonance Imaging in Liver Biomechanics: A Systematic Review.Frontiers in physiology · 2021Pooled it
- Lumped parameter modeling of changes in liver hemodynamics due to cirrhosis.Biomechanics and modeling in mechanobiology · 2026Article
- An agent-based model suggests how senescent cell behavior and matrix mechanics drive pulmonary fibrosis in aged mice.bioRxiv : the preprint server for biology · 2026Article
- Preclinical approaches to studying liver and kidney fibrosis: models and methodologies.Frontiers in pharmacology · 2026Review
- Quantitative systems toxicology approach that integrates PBPK and core hepatic metabolism: a case study with valproic acid.Frontiers in pharmacology · 2026Article
- Quantitative Approaches to Accelerate MASH Drug Discovery and Development.Clinical pharmacology and therapeutics · 2025Review
- A rule-based multiscale model of hepatic stellate cell plasticity: Critical role of the inactivation loop in fibrosis progression.PLoS computational biology · 2024Article
- SimuCell3D: three-dimensional simulation of tissue mechanics with cell polarization.Nature computational science · 2024Article
- Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy.Cancers · 2024Review
- A liver digital twin for in silico testing of cellular and inter-cellular mechanisms in regeneration after drug-induced damage.iScience · 2024Article
- Computational simulation of liver fibrosis dynamics.Scientific reports · 2022Article
- Computational models in systems biology: standards, dissemination, and best practices.Current opinion in biotechnology · 2022Review
- From Seeing to Simulating: A Survey of Imaging Techniques and Spatially-Resolved Data for Developing Multiscale Computational Models of Liver Regeneration.Frontiers in systems biology · 2022Article
- Article
- Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach.Scientific reports · 2021Article
- Multiscale Computational Modeling of Vascular Adaptation: A Systems Biology Approach Using Agent-Based Models.Frontiers in bioengineering and biotechnology · 2021Review
- Multi-scale models of lung fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2020Review
- Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis.Frontiers in bioengineering and biotechnology · 2020Review
- Agent-based models of inflammation in translational systems biology: A decade later.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Computational/experimental evaluation of liver metastasis post hepatic injury: interactions with macrophages and transitional ECM.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic hepatic inflammation involves a complex interplay of inflammatory and mechanical influences, ultimately manifesting in a characteristic histopathology of liver fibrosis. We created an agent-based model (ABM) of liver tissue in order to computationally examine the consequence of liver inflammation. Our liver fibrosis ABM (LFABM) is comprised of literature-derived rules describing molecular and histopathological aspects of inflammation and fibrosis in a section of chemically injured liver. Hepatocytes are modeled as agents within hexagonal lobules. Injury triggers an inflammatory reaction, which leads to activation of local Kupffer cells and recruitment of monocytes from circulation. Portal fibroblasts and hepatic stellate cells are activated locally by the products of inflammation. The various agents in the simulation are regulated by above-threshold concentrations of pro- and anti-inflammatory cytokines and damage-associated molecular pattern molecules. The simulation progresses from chronic inflammation to collagen deposition, exhibiting periportal fibrosis followed by bridging fibrosis, and culminating in disruption of the regular lobular structure. The ABM exhibited key histopathological features observed in liver sections from rats treated with carbon tetrachloride (CCl4). An in silico "tension test" for the hepatic lobules predicted an overall increase in tissue stiffness, in line with clinical elastography literature and published studies in CCl4-treated rats. Therapy simulations suggested differential anti-fibrotic effects of neutralizing tumor necrosis factor alpha vs. enhancing M2 Kupffer cells. We conclude that a computational model of liver inflammation on a structural skeleton of physical forces can recapitulate key histopathological and macroscopic properties of CCl4-injured liver. This multiscale approach linking molecular and chemomechanical stimuli enables a model that could be used to gain translationally relevant insights into liver fibrosis.
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Registered trials
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