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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, 23 (22)
doi: 10.3390/ijms232213920
Artikel, Bibliographie

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Kurzbeschreibung (Abstract)

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.

Typ des Eintrags: Artikel
Erschienen: 2022
Autor(en): Cogno, Nicolò ; Bauer, Roman ; Durante, Marco
Art des Eintrags: Bibliographie
Titel: An Agent-Based Model of Radiation-Induced Lung Fibrosis
Sprache: Englisch
Publikationsjahr: 2022
Ort: Darmstadt
Verlag: MDPI
Titel der Zeitschrift, Zeitung oder Schriftenreihe: International Journal of Molecular Sciences
Jahrgang/Volume einer Zeitschrift: 23
(Heft-)Nummer: 22
Kollation: 21 Seiten
DOI: 10.3390/ijms232213920
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Kurzbeschreibung (Abstract):

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.

Freie Schlagworte: agent-based modelling, RILF, IPF, senescence, bystander, 3D modelling, NTCP
Zusätzliche Informationen:

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

Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 530 Physik
Fachbereich(e)/-gebiet(e): 05 Fachbereich Physik
05 Fachbereich Physik > Institut für Physik Kondensierter Materie (IPKM)
Hinterlegungsdatum: 02 Aug 2024 12:46
Letzte Änderung: 02 Aug 2024 12:46
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