Topographic distribution of idiopathic pulmonary fibrosis: a hybrid physics- and agent-based model

Wellman, Tyler J.; Mondoñedo, Jarred R.; Davis, Gerald S.; Bates, Jason H. T.; Suki, Bélâ

doi:10.1088/1361-6579/aaca86

Cited by 23 publications

(33 citation statements)

References 43 publications

(73 reference statements)

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“…2 ) 135 . Further evidence has been derived from mathematical models, in which increased stiffness of the visceral pleura, e.g., following EMT and matrix synthesis, is predicted to be key in driving mechanotransduction pathways to propel a fibroblast activation chain towards the parenchyma 136 . In support of this, the pleura and underlying parenchyma of human IPF patients show strong immuno-labelling for MSLN, WT1 or calretinin 130 , 137 , 138 , and when isolated and cultured display increased contractility and movement compared to healthy mesothelium 130 .…”

Section: Injury and Disease In Adult Life: Recapitulation Of Coelomicmentioning

confidence: 99%

Mesothelial to mesenchyme transition as a major developmental and pathological player in trunk organs and their cavities

Koopmans

Rinkevich

2018

Commun Biol

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The internal organs embedded in the cavities are lined by an epithelial monolayer termed the mesothelium. The mesothelium is increasingly implicated in driving various internal organ pathologies, as many of the normal embryonic developmental pathways acting in mesothelial cells, such as those regulating epithelial-to-mesenchymal transition, also drive disease progression in adult life. Here, we summarize observations from different animal models and organ systems that collectively point toward a central role of epithelial-to-mesenchymal transition in driving tissue fibrosis, acute scarring, and cancer metastasis. Thus, drugs targeting pathways of mesothelium’s transition may have broad therapeutic benefits in patients suffering from these diseases.

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Section: Injury and Disease In Adult Life: Recapitulation Of Coelomicmentioning

confidence: 99%

Mesothelial to mesenchyme transition as a major developmental and pathological player in trunk organs and their cavities

Koopmans

Rinkevich

2018

Commun Biol

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“…How does this pathological change in the ECM spread? Current theories 31,32 require cells to migrate into the region of stiffer ECM for them to sense the altered matrix and respond by excessive secretion of matrix proteins thereby creating a positive feedback loop that leads to spread of this disease. However, given the collective nature of ECM stiffness sensing in SMC clusters, it may be possible for SMCs located far away from the site of ECM remodeling to detect this localized change even though these SMCs are not physically in contact with the stiff ECM.…”

Section: The Effect Of Localized Ecm Stiffening Can Be Sensed By Smcsmentioning

confidence: 99%

Intercellular communication controls agonist-induced calcium oscillations independently of gap junctions in smooth muscle cells

Stasiak

Jamieson

Bouffard

et al. 2019

Preprint

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Agonist-induced calcium oscillations constitute a critical part of the machinery by which smooth muscle cells (SMCs) regulate constriction in airways and the vasculature. The frequency of these Ca 2+ oscillations encodes the concentration of contractile agonist detected by the surface receptors on the SMC, with higher frequencies corresponding to higher agonist concentrations. Here, we report a collective phenomenon in SMCs where cells in multicellular ensembles exhibit synchronous agonist-induced Ca 2+ oscillations and increased Ca 2+ oscillation frequencies on stiffer substrates. This phenomenon is absent in isolated SMCs. We show that intercellular communication that enables this collective Ca 2+ response in SMCs does not involve transport across gap junctions or extracellular diffusion of signaling molecules. Instead, our data support a model in which force-transfer among SMCs regulates their agonist response. This collective response could influence asthma and hypertension at an early stage and also cause the pathology to progress much faster than currently believed.

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“…Another approach that has been used to both increase computational efficiency and improved model fidelity is the increasing use of "hybrid" models that combine the discrete elements of an ABM with functions better represented by differential equations. This is a natural convergence between ABMs and equation-based models, as more detailed rules for ABMs are expressible as mathematical functions, while increased compartmentalization and spatial discretization increase the ability of equation-based models to capture the heterogeneity and structural features of biological systems (see Ceresa et al, 2018;Cilfone et al, 2015;Dutta-Moscato et al, 2014;Marino et al, 2011;Marino & Kirschner, 2016;Mayorga, Cebrian, Verma, Hoops, & Bassaganya-Riera, 2018;Solovyev et al, 2013;Wellman et al, 2018).…”

Section: Methodological and Technological Developmentsmentioning

confidence: 99%

“…The authors validated key patterns and features from their ABM experimentally in lung histology sections from mice exposed to tobacco smoke. More recently, Wellman et al (2018) and Ceresa et al (2018) extended this work through the use of hybrid modeling approaches. Ceresa et al (2018) generated a hybrid finite-element model/ABM of COPD and tested key features against publicly available databases.…”

Section: Pulmonary Inflammationmentioning

confidence: 99%

Agent‐based models of inflammation in translational systems biology: A decade later

Vodovotz

2019

WIREs Mechanisms of Disease

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Agent‐based modeling is a rule‐based, discrete‐event, and spatially explicit computational modeling method that employs computational objects that instantiate the rules and interactions among the individual components (“agents”) of system. Agent‐based modeling is well suited to translating into a computational model the knowledge generated from basic science research, particularly with respect to translating across scales the mechanisms of cellular behavior into aggregated cell population dynamics manifesting at the tissue and organ level. This capacity has made agent‐based modeling an integral method in translational systems biology (TSB), an approach that uses multiscale dynamic computational modeling to explicitly represent disease processes in a clinically relevant fashion. The initial work in the early 2000s using agent‐based models (ABMs) in TSB focused on examining acute inflammation and its intersection with wound healing; the decade since has seen vast growth in both the application of agent‐based modeling to a wide array of disease processes as well as methodological advancements in the use and analysis of ABM. This report presents an update on an earlier review of ABMs in TSB and presents examples of exciting progress in the modeling of various organs and diseases that involve inflammation. This review also describes developments that integrate the use of ABMs with cutting‐edge technologies such as high‐performance computing, machine learning, and artificial intelligence, with a view toward the future integration of these methodologies. This article is categorized under: Translational, Genomic, and Systems Medicine > Translational Medicine Models of Systems Properties and Processes > Mechanistic Models Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models Models of Systems Properties and Processes > Organismal Models

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Topographic distribution of idiopathic pulmonary fibrosis: a hybrid physics- and agent-based model

Abstract: We conclude that the clinical manifestation of subpleural honeycombing in IPF may result from fibroblasts entering into a positive feedback loop induced by the abnormally high tissue stiffness near the pleura.

Cited by 23 publications

References 43 publications

Mesothelial to mesenchyme transition as a major developmental and pathological player in trunk organs and their cavities

Mesothelial to mesenchyme transition as a major developmental and pathological player in trunk organs and their cavities

Intercellular communication controls agonist-induced calcium oscillations independently of gap junctions in smooth muscle cells

Agent‐based models of inflammation in translational systems biology: A decade later

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