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Treatment with nintedanib attenuates fibrosis in a new humanized mouse model for idiopathic pulmonary fibrosis

 
: Plappert, Linda; Jäger, Benedikt; Kraus, Kim Jessica; Wollin, Lutz; Prasse, Antje

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Pneumologie 72 (2018), Nr.3, S.229
ISSN: 0934-8387
Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin, Sektionen Zellbiologie und Infektiologie (Herbsttagung) <2017, Gießen>
Englisch
Abstract
Fraunhofer ITEM ()

Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with mean survival time of about 3 years. Nintedanib was recently approved for the treatment of IPF. Our previous work suggested a pathogenic role of airway basal cells (ABC) in IPF. In order to test this we established a new humanized mouse model based on primary ABC lines derived from IPF patients. This mouse models resembles histomorphological changes of IPF including honeycomb cyst formation.
Objectives: The aim of our study was to test the effect of nintedanib treatment in our newly established humanized mouse model of IPF.Methods:C57/B6N Rag2 KO mice, between 6 – 11 weeks old, were used in the study. At day 0 a low dose of bleomycin was injected i.t. under light anesthesia. Three days later human ABCs from IPF patients (n = 22) were injected i.t. in a pair of C57/B6N Rag2 KO mice. For each cell line we tested the effect of nintedanib treatment twice daily versus PBS (control). Lungs were harvested at day 21. Formalin fixed paraffin embedded lung tissues were used for Masson trichrome stain and Ashcroft score. Lung function was measured using a standard protocol and hydroxyproline levels were determined by a commercially available kit.
Results: Histomorphological analysis including Ashcroft score showed a statistically significant decrease in fibrotic lesions of mice treated with nintedanib. In line with that we also observed significantly lower hydroxyproline levels in mice treated with nintedanib. Lung function test and BAL differential counts did not reveal any significant differences.
Conclusion: Our data demonstrate an ameliorating effect of nintedanib treatment in our newly established humanized mouse model of IPF which is based on lung tissue remodeling elicited by ABCs from IPF patients.

: http://publica.fraunhofer.de/dokumente/N-559349.html