A mouse model of progressive lung fibrosis with cutaneous involvement induced by a combination of oropharyngeal and osmotic minipump bleomycin delivery

Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously reso...

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Published inAmerican journal of physiology. Lung cellular and molecular physiology Vol. 326; no. 6; pp. L736 - L753
Main Authors Grandi, Andrea, Ferrini, Erica, Zoboli, Matteo, Buseghin, Davide, Pennati, Francesca, Khalajzeyqami, Zahra, Ciccimarra, Roberta, Villetti, Gino, Stellari, Franco Fabio
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Published United States American Physiological Society 01.06.2024
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Abstract Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at , , and , including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD. This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.
AbstractList Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at days 28, 35, and 42, including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD.NEW & NOTEWORTHY This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at days 28, 35, and 42, including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD.NEW & NOTEWORTHY This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.
Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at days 28 , 35 , and 42 , including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD. NEW & NOTEWORTHY This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.
This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD. Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at days 28, 35, and 42, including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD. NEW & NOTEWORTHY This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.
Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at days 28, 35, and 42, including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD.
Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at , , and , including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD. This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.
Author Buseghin, Davide
Pennati, Francesca
Khalajzeyqami, Zahra
Ciccimarra, Roberta
Villetti, Gino
Stellari, Franco Fabio
Ferrini, Erica
Grandi, Andrea
Zoboli, Matteo
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Cites_doi 10.1369/0022155417718541
10.1080/14397595.2019.1696505
10.1371/journal.pone.0270005
10.1038/s41598-020-71293-3
10.1007/s11926-019-0831-z
10.1038/labinvest.2014.145
10.26502/fccm.92920302
10.1016/j.mbplus.2021.100099
10.1152/ajplung.00210.2013
10.3389/fmed.2017.00118
10.1165/rcmb.2018-0147OC
10.1056/nejmoa1903076
10.3389/fvets.2020.588592
10.1183/13993003.02026-2019
10.1016/j.autrev.2021.102978
10.1111/ijd.15388
10.1152/ajplung.00180.2022
10.1136/jcp.41.4.467
10.1016/j.rmcr.2023.101921
10.1038/s41584-022-00864-7
10.1152/ajplung.00311.2019
10.2144/000112729
10.1136/annrheumdis-2016-210823
10.3390/immuno2030034
10.1056/NEJMra2005230
10.3389/fphar.2020.01117
10.1186/ar4070
10.1136/annrheumdis-2015-208029
10.1038/s41598-017-17204-5
10.1007/s10565-021-09676-z
10.3390/bioengineering8050063
10.1073/pnas.0801414105
10.1016/S2213-2600(20)30330-1
10.1038/s41598-021-97728-z
10.1186/s40248-017-0089-0
10.1359/jbmr.2002.17.7.1180
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Snippet Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for...
This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with...
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SubjectTerms Animal models
Animals
Biomarkers
Bleomycin
Bleomycin - administration & dosage
Bleomycin - toxicity
Computed tomography
Disease Models, Animal
Drug therapy
Female
Fibrosis
Histology
Hypodermis
Immunofluorescence
Lung - diagnostic imaging
Lung - drug effects
Lung - pathology
Lung diseases
Lung Diseases, Interstitial - chemically induced
Lung Diseases, Interstitial - diagnostic imaging
Lung Diseases, Interstitial - drug therapy
Lung Diseases, Interstitial - pathology
Medical imaging
Methods and Resources
Mice
Mice, Inbred C57BL
Oropharynx - diagnostic imaging
Oropharynx - drug effects
Oropharynx - pathology
Pulmonary Fibrosis - chemically induced
Pulmonary Fibrosis - drug therapy
Pulmonary Fibrosis - pathology
Scleroderma, Systemic - complications
Scleroderma, Systemic - drug therapy
Scleroderma, Systemic - pathology
Skin - drug effects
Skin - pathology
Systemic sclerosis
Thickness
Time dependence
X-Ray Microtomography
Title A mouse model of progressive lung fibrosis with cutaneous involvement induced by a combination of oropharyngeal and osmotic minipump bleomycin delivery
URI https://www.ncbi.nlm.nih.gov/pubmed/38651940
https://www.proquest.com/docview/3063796653
https://www.proquest.com/docview/3045116759
https://pubmed.ncbi.nlm.nih.gov/PMC11381007
Volume 326
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