LATE-BREAKING ABSTRACT: Anti-fibrotic effects of nintedanib and pirfenidone in 2D versus 3D lung cultures

Lehmann, Mareike; Buhl, Lara; Wagner, Darcy E.; Behr, Jürgen; Lindner, Michael; Königshoff, Mélanie

doi:10.1183/13993003.congress-2016.oa478

Cited by 2 publications

(1 citation statement)

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“…Preliminary studies treating slices with bleomycin, or influenza, have not yielded changes ex vivo that are observed in vivo (29,73), although encouraging results using TGF-b have been found (102). It is possible to generate lung slices from mice that have been treated with bleomycin in vivo, and these have increased levels of extracellular matrix (103-105); there are encouraging results using nintedanib and pirfenidone in these slices as well (102). An important feature of murine or human lung slice cultures is that they can be used to assess effects of drugs directly on structural cells in the absence of vasculature or inflammatory cell influx.…”

Section: Ex Vivo Lung Slices For Preclinical Testingmentioning

confidence: 99%

An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis

Jenkins

Moore

Chambers

et al. 2017

Am J Respir Cell Mol Biol

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Numerous compounds have shown efficacy in limiting development of pulmonary fibrosis using animal models, yet few of these compounds have replicated these beneficial effects in clinical trials. Given the challenges associated with performing clinical trials in patients with idiopathic pulmonary fibrosis (IPF), it is imperative that preclinical data packages be robust in their analyses and interpretations to have the best chance of selecting promising drug candidates to advance to clinical trials. The American Thoracic Society has convened a group of experts in lung fibrosis to discuss and formalize recommendations for preclinical assessment of antifibrotic compounds. The panel considered three major themes (choice of animal, practical considerations of fibrosis modeling, and fibrotic endpoints for evaluation). Recognizing the need for practical considerations, we have taken a pragmatic approach. The consensus view is that use of the murine intratracheal bleomycin model in animals of both genders, using hydroxyproline measurements for collagen accumulation along with histologic assessments, is the best-characterized animal model available for preclinical testing. Testing of antifibrotic compounds in this model is recommended to occur after the acute inflammatory phase has subsided (generally after Day 7). Robust analyses may also include confirmatory studies in human IPF specimens and validation of results in a second system using in vivo or in vitro approaches. The panel also strongly encourages the publication of negative results to inform the lung fibrosis community. These recommendations are for preclinical therapeutic evaluation only and are not intended to dissuade development of emerging technologies to better understand IPF pathogenesis.

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Section: Ex Vivo Lung Slices For Preclinical Testingmentioning

confidence: 99%

An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis

Jenkins

Moore

Chambers

et al. 2017

Am J Respir Cell Mol Biol

Self Cite

300

254

View full text Add to dashboard Cite

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Pulmonary fibrosis: risk factors, pathogenesis and <i>in vivo/in vitro</i> experimental modeling

Chistyakova

2023

Genes & Cells

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Pulmonary fibrosis is a group of lung diseases characterized by scar formation and interstitial pneumonia with a mean life expectancy of 3-5 yearspost diagnosis. Risk factors for developing IPF include external (environment) and internal (genetic risk factors). The central role in the formation of fibrosis is played by the massive myofibroblasts and the excessive deposition of extracellular matrix, including collagen I type. The main approaches for PF treatment is either lung transplantation or therapeutic treatment by antifibrotic drugs. However, for both approaches there are a number of limitations, for surgical the lack of donor organs and immune rejection of transplanted tissues, for therapeutic the drugs that are identified in animal studies fail in human clinical trials. Thus, there is a necessity for advancing of humanized in vitro models to improve treatments prior to human clinical trials. The development of different tissue (two-, three-dimensional) models has created systems capable of emulating human lung structure, function, and cell and matrix interactions, which have shown potential for in vitro drug testing. In this review, we focused on PF risk factors, development mechanisms, and a review of the main in vitro and in vivo models for studying PF.

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LATE-BREAKING ABSTRACT: Anti-fibrotic effects of nintedanib and pirfenidone in 2D versus 3D lung cultures

Cited by 2 publications

References 0 publications

An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis

An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis

Pulmonary fibrosis: risk factors, pathogenesis and <i>in vivo/in vitro</i> experimental modeling

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