Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.945134/full |
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| author | Esther Marhuenda Esther Marhuenda Alvaro Villarino Maria Narciso Maria Narciso Linda Elowsson Isaac Almendros Isaac Almendros Isaac Almendros Gunilla Westergren-Thorsson Ramon Farré Ramon Farré Ramon Farré Núria Gavara Núria Gavara Núria Gavara Jorge Otero Jorge Otero Jorge Otero |
| author_facet | Esther Marhuenda Esther Marhuenda Alvaro Villarino Maria Narciso Maria Narciso Linda Elowsson Isaac Almendros Isaac Almendros Isaac Almendros Gunilla Westergren-Thorsson Ramon Farré Ramon Farré Ramon Farré Núria Gavara Núria Gavara Núria Gavara Jorge Otero Jorge Otero Jorge Otero |
| author_sort | Esther Marhuenda |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T21:09:20Z |
| format | Article |
| id | doaj.art-fada4b93ac8b441286b7787de3dd6395 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T21:09:20Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-fada4b93ac8b441286b7787de3dd63952022-12-22T04:03:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.945134945134Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devicesEsther Marhuenda0Esther Marhuenda1Alvaro Villarino2Maria Narciso3Maria Narciso4Linda Elowsson5Isaac Almendros6Isaac Almendros7Isaac Almendros8Gunilla Westergren-Thorsson9Ramon Farré10Ramon Farré11Ramon Farré12Núria Gavara13Núria Gavara14Núria Gavara15Jorge Otero16Jorge Otero17Jorge Otero18Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, University de Barcelona, Barcelona, SpainCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, University de Barcelona, Barcelona, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, University de Barcelona, Barcelona, SpainThe Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, SpainLung Biology, Biomedical Center, Department of Medical Science,Lund University, Lund, SwedenUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, University de Barcelona, Barcelona, SpainCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainLung Biology, Biomedical Center, Department of Medical Science,Lund University, Lund, SwedenUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, University de Barcelona, Barcelona, SpainCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, University de Barcelona, Barcelona, SpainCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainThe Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, University de Barcelona, Barcelona, SpainCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, SpainThe Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, SpainAcute 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.945134/fullARDSlung-on-a-chipextracellular matrixhydrogelsmesenchymal stromal cellsalveolar epithelial cells |
| spellingShingle | Esther Marhuenda Esther Marhuenda Alvaro Villarino Maria Narciso Maria Narciso Linda Elowsson Isaac Almendros Isaac Almendros Isaac Almendros Gunilla Westergren-Thorsson Ramon Farré Ramon Farré Ramon Farré Núria Gavara Núria Gavara Núria Gavara Jorge Otero Jorge Otero Jorge Otero Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices Frontiers in Pharmacology ARDS lung-on-a-chip extracellular matrix hydrogels mesenchymal stromal cells alveolar epithelial cells |
| title | Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices |
| title_full | Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices |
| title_fullStr | Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices |
| title_full_unstemmed | Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices |
| title_short | Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices |
| title_sort | development of a physiomimetic model of acute respiratory distress syndrome by using ecm hydrogels and organ on a chip devices |
| topic | ARDS lung-on-a-chip extracellular matrix hydrogels mesenchymal stromal cells alveolar epithelial cells |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.945134/full |
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