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Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues
BACKGROUND: In recent years, there have been breakthroughs in the preclinical research of respiratory diseases, such as organoids and organ tissue chip models, but they still cannot provide insight into human respiratory diseases well. Human lung slices model provides a promising in vitro model for...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061769/ https://www.ncbi.nlm.nih.gov/pubmed/36998092 http://dx.doi.org/10.1186/s40001-023-01104-8 |
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author | Sun, Ying Jing, Pengyu Gan, Helina Wang, Xuejiao Zhu, Ximing Fan, Jiangjiang Li, Haichao Zhang, Zhipei Lin, James Chi Jen Gu, Zhongping |
author_facet | Sun, Ying Jing, Pengyu Gan, Helina Wang, Xuejiao Zhu, Ximing Fan, Jiangjiang Li, Haichao Zhang, Zhipei Lin, James Chi Jen Gu, Zhongping |
author_sort | Sun, Ying |
collection | PubMed |
description | BACKGROUND: In recent years, there have been breakthroughs in the preclinical research of respiratory diseases, such as organoids and organ tissue chip models, but they still cannot provide insight into human respiratory diseases well. Human lung slices model provides a promising in vitro model for the study of respiratory diseases because of its preservation of lung structure and major cell types. METHODS: Human lung slices were manually prepared from small pieces of lung tissues obtained from lung cancer patients subjected to lung surgery. To evaluate the suitability of this model for lung fibrosis research, lung slices were treated with CdCl(2) (30 μM), TGF-β1 (1 ng/ml) or CdCl(2) plus TGF-β1 for 3 days followed by toxicity assessment, gene expression analysis and histopathological observations. RESULTS: CdCl(2) treatment resulted in a concentration-dependent toxicity profile evidenced by MTT assay as well as histopathological observations. In comparison with the untreated group, CdCl(2) and TGF-β1 significantly induces MMP2 and MMP9 gene expression but not MMP1. Interestingly, CdCl(2) plus TGF-β1 significantly induces the expression of MMP1 but not MMP2, MMP7 or MMP9. Microscopic observations reveal the pathogenesis of interstitial lung fibrosis in the lung slices of all groups; however, CdCl(2) plus TGF-β1 treatment leads to a greater alveolar septa thickness and the formation of fibroblast foci-like pathological features. The lung slice model is in short of blood supply and the inflammatory/immune-responses are considered minimal. CONCLUSIONS: The results are in favor of the hypothesis that idiopathic pulmonary fibrosis (IPF) is mediated by tissue damage and abnormal repair. Induction of MMP1 gene expression and fibroblast foci-like pathogenesis suggest that this model might represent an early stage of IPF. |
format | Online Article Text |
id | pubmed-10061769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100617692023-03-31 Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues Sun, Ying Jing, Pengyu Gan, Helina Wang, Xuejiao Zhu, Ximing Fan, Jiangjiang Li, Haichao Zhang, Zhipei Lin, James Chi Jen Gu, Zhongping Eur J Med Res Research BACKGROUND: In recent years, there have been breakthroughs in the preclinical research of respiratory diseases, such as organoids and organ tissue chip models, but they still cannot provide insight into human respiratory diseases well. Human lung slices model provides a promising in vitro model for the study of respiratory diseases because of its preservation of lung structure and major cell types. METHODS: Human lung slices were manually prepared from small pieces of lung tissues obtained from lung cancer patients subjected to lung surgery. To evaluate the suitability of this model for lung fibrosis research, lung slices were treated with CdCl(2) (30 μM), TGF-β1 (1 ng/ml) or CdCl(2) plus TGF-β1 for 3 days followed by toxicity assessment, gene expression analysis and histopathological observations. RESULTS: CdCl(2) treatment resulted in a concentration-dependent toxicity profile evidenced by MTT assay as well as histopathological observations. In comparison with the untreated group, CdCl(2) and TGF-β1 significantly induces MMP2 and MMP9 gene expression but not MMP1. Interestingly, CdCl(2) plus TGF-β1 significantly induces the expression of MMP1 but not MMP2, MMP7 or MMP9. Microscopic observations reveal the pathogenesis of interstitial lung fibrosis in the lung slices of all groups; however, CdCl(2) plus TGF-β1 treatment leads to a greater alveolar septa thickness and the formation of fibroblast foci-like pathological features. The lung slice model is in short of blood supply and the inflammatory/immune-responses are considered minimal. CONCLUSIONS: The results are in favor of the hypothesis that idiopathic pulmonary fibrosis (IPF) is mediated by tissue damage and abnormal repair. Induction of MMP1 gene expression and fibroblast foci-like pathogenesis suggest that this model might represent an early stage of IPF. BioMed Central 2023-03-30 /pmc/articles/PMC10061769/ /pubmed/36998092 http://dx.doi.org/10.1186/s40001-023-01104-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Sun, Ying Jing, Pengyu Gan, Helina Wang, Xuejiao Zhu, Ximing Fan, Jiangjiang Li, Haichao Zhang, Zhipei Lin, James Chi Jen Gu, Zhongping Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues |
title | Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues |
title_full | Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues |
title_fullStr | Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues |
title_full_unstemmed | Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues |
title_short | Evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues |
title_sort | evaluation of an ex vivo fibrogenesis model using human lung slices prepared from small tissues |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061769/ https://www.ncbi.nlm.nih.gov/pubmed/36998092 http://dx.doi.org/10.1186/s40001-023-01104-8 |
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