Academic Journal

Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices

التفاصيل البيبلوغرافية
العنوان: Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices
المؤلفون: Esther Marhuenda, Alvaro Villarino, Maria Narciso, Linda Elowsson, Isaac Almendros, Gunilla Westergren-Thorsson, Ramon Farré, Núria Gavara, Jorge Otero
المصدر: Frontiers in Pharmacology, Vol 13 (2022)
بيانات النشر: Frontiers Media S.A., 2022.
سنة النشر: 2022
المجموعة: LCC:Therapeutics. Pharmacology
مصطلحات موضوعية: ARDS, lung-on-a-chip, extracellular matrix, hydrogels, mesenchymal stromal cells, alveolar epithelial cells, Therapeutics. Pharmacology, RM1-950
الوصف: Acute Respiratory Distress Syndrome is one of the more common fatal complications in COVID-19, characterized by a highly aberrant inflammatory response. Pre-clinical models to study the effect of cell therapy and anti-inflammatory treatments have not comprehensively reproduced the disease due to its high complexity. This work presents a novel physiomimetic in vitro model for Acute Respiratory Distress Syndrome using lung extracellular matrix-derived hydrogels and organ-on-a-chip devices. Monolayres of primary alveolar epithelial cells were cultured on top of decellullarized lung hydrogels containing primary lung mesenchymal stromal cells. Then, cyclic stretch was applied to mimic breathing, and an inflammatory response was induced by using a bacteriotoxin hit. Having simulated the inflamed breathing lung environment, we assessed the effect of an anti-inflammatory drug (i.e., dexamethasone) by studying the secretion of the most relevant inflammatory cytokines. To better identify key players in our model, the impact of the individual factors (cyclic stretch, decellularized lung hydrogel scaffold, and the presence of mesenchymal stromal cells) was studied separately. Results showed that developed model presented a more reduced inflammatory response than traditional models, which is in line with what is expected from the response commonly observed in patients. Further, from the individual analysis of the different stimuli, it was observed that the use of extracellular matrix hydrogels obtained from decellularized lungs had the most significant impact on the change of the inflammatory response. The developed model then opens the door for further in vitro studies with a better-adjusted response to the inflammatory hit and more robust results in the test of different drugs or cell therapy.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1663-9812
Relation: https://www.frontiersin.org/articles/10.3389/fphar.2022.945134/full; https://doaj.org/toc/1663-9812
DOI: 10.3389/fphar.2022.945134
URL الوصول: https://doaj.org/article/fada4b93ac8b441286b7787de3dd6395
رقم الانضمام: edsdoj.fada4b93ac8b441286b7787de3dd6395
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:16639812
DOI:10.3389/fphar.2022.945134