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An Agent-Based Model of Radiation-Induced Lung Fibrosis

Cogno, Nicolò ; Bauer, Roman ; Durante, Marco (2022)
An Agent-Based Model of Radiation-Induced Lung Fibrosis.
In: International Journal of Molecular Sciences, 2022, 23 (22)
doi: 10.26083/tuprints-00022973
Article, Secondary publication, Publisher's Version

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Item Type: Article
Type of entry: Secondary publication
Title: An Agent-Based Model of Radiation-Induced Lung Fibrosis
Language: English
Date: 19 December 2022
Place of Publication: Darmstadt
Year of primary publication: 2022
Publisher: MDPI
Journal or Publication Title: International Journal of Molecular Sciences
Volume of the journal: 23
Issue Number: 22
Collation: 21 Seiten
DOI: 10.26083/tuprints-00022973
Corresponding Links:
Origin: Secondary publication DeepGreen

Early- and late-phase radiation-induced lung injuries, namely pneumonitis and lung fibrosis (RILF), severely constrain the maximum dose and irradiated volume in thoracic radiotherapy. As the most radiosensitive targets, epithelial cells respond to radiation either by undergoing apoptosis or switching to a senescent phenotype that triggers the immune system and damages surrounding healthy cells. Unresolved inflammation stimulates mesenchymal cells’ proliferation and extracellular matrix (ECM) secretion, which irreversibly stiffens the alveolar walls and leads to respiratory failure. Although a thorough understanding is lacking, RILF and idiopathic pulmonary fibrosis share multiple pathways and would mutually benefit from further insights into disease progression. Furthermore, current normal tissue complication probability (NTCP) models rely on clinical experience to set tolerance doses for organs at risk and leave aside mechanistic interpretations of the undergoing processes. To these aims, we implemented a 3D agent-based model (ABM) of an alveolar duct that simulates cell dynamics and substance diffusion following radiation injury. Emphasis was placed on cell repopulation, senescent clearance, and intra/inter-alveolar bystander senescence while tracking ECM deposition. Our ABM successfully replicates early and late fibrotic response patterns reported in the literature along with the ECM sigmoidal dose-response curve. Moreover, surrogate measures of RILF severity via a custom indicator show qualitative agreement with published fibrosis indices. Finally, our ABM provides a fully mechanistic alveolar survival curve highlighting the need to include bystander damage in lung NTCP models.

Uncontrolled Keywords: agent-based modelling, RILF, IPF, senescence, bystander, 3D modelling, NTCP
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-229737
Additional Information:

This article belongs to the Special Issue Molecular and Cellular Mechanisms of Idiopathic Pulmonary Fibrosis and Interstitial Lung Diseases

Classification DDC: 500 Science and mathematics > 530 Physics
Divisions: 05 Department of Physics > Institute for Condensed Matter Physics
Date Deposited: 19 Dec 2022 12:41
Last Modified: 14 Nov 2023 19:05
SWORD Depositor: Deep Green
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/22973
PPN: 50324192X
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