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Ex vivo micro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation.

Scotton, CJ; Hayes, B; Alexander, R; Datta, A; Forty, EJ; Mercer, PF; Blanchard, A; (2013) Ex vivo micro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation. Eur Respir J , 42 (6) 1633 - 1645. 10.1183/09031936.00182412. Green open access

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Abstract

Research into the pathogenesis underlying the development of idiopathic pulmonary fibrosis is hampered by a repertoire of animal models that fail to recapitulate all the features of the human disease. Better use and understanding of what the animal models represent may improve clinical predictability. We interrogated ex vivo micro-computed tomography (CT) as a novel end-point measure in the mouse model of bleomycin-induced lung fibrosis (BILF), and to evaluate a therapeutic dosing regimen for preclinical drug evaluation. A detailed characterisation of BILF was performed using standard end-point measures (lung hydroxyproline and histology). High resolution micro-CT (∼13.7 μm voxel size) was evaluated for quantifying the extent and severity of lung fibrosis. The period from 14 to 28 days following bleomycin instillation represents progression of established fibrosis. A therapeutic dosing regimen during this period was validated using a transforming growth factor-β receptor-1 kinase inhibitor, and micro-CT provided a highly sensitive and quantitative measure of fibrosis. Moreover, fibrotic lesions did not completely resolve, but instead persisted for ≥6 months following a single insult with bleomycin. Ex vivo micro-CT analysis of BILF allows robust evaluation of therapeutic dosing once fibrosis is already well established, requiring fewer mice than conventional biochemical end-points.

Type: Article
Title: Ex vivo micro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1183/09031936.00182412
Publisher version: http://dx.doi.org/10.1183/09031936.00182412
Language: English
Additional information: © ERS 2013. ERJ Open articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 3.0.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1389549
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