A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response
Abstract This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre‐clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co‐cultu...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10715 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841553659895218176 |
|---|---|
| author | Clémentine Richter Lorenz Latta Daria Harig Patrick Carius Janick D. Stucki Nina Hobi Andreas Hugi Paul Schumacher Tobias Krebs Alexander Gamrekeli Felix Stöckle Klaus Urbschat Galia Montalvo Franziska Lautenschläger Brigitta Loretz Alberto Hidalgo Nicole Schneider‐Daum Claus‐Michael Lehr |
| author_facet | Clémentine Richter Lorenz Latta Daria Harig Patrick Carius Janick D. Stucki Nina Hobi Andreas Hugi Paul Schumacher Tobias Krebs Alexander Gamrekeli Felix Stöckle Klaus Urbschat Galia Montalvo Franziska Lautenschläger Brigitta Loretz Alberto Hidalgo Nicole Schneider‐Daum Claus‐Michael Lehr |
| author_sort | Clémentine Richter |
| collection | DOAJ |
| description | Abstract This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre‐clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co‐cultured with macrophages differentiated from the THP‐1 cell line, creating a physiological biological microenvironment. To mimic the three‐dimensional architecture and dynamic expansion and relaxation of the air‐blood‐barrier, they are grown on a stretchable microphysiological lung‐on‐chip. For validating the in vitro model, three different protocols have been developed to demonstrate the clinically established anti‐inflammatory effect of glucocorticoids to reduce certain inflammatory markers after different pro‐inflammatory stimuli: (1) an inflammation caused by bacterial LPS (lipopolysaccharides) to simulate an LPS‐induced acute lung injury measured best with cytokine IL‐6 release; (2) an inflammation caused by LPS at ALI (air‐liquid interface) to investigate aerosolized anti‐inflammatory treatment, measured with chemokine IL‐8 release; and (3) an inflammation with a combination of human inflammatory cytokines TNFα and IFNγ to simulate a critical cytokine storm leading to epithelial barrier disruption, where the eventual weakening or protection of the epithelial barrier can be measured. In all cases, the presence of macrophages appeared to be crucial to mediating inflammatory changes in the alveolar epithelium. LPS induction led to inflammatory changes independently of stretch conditions. Dynamic stretch, emulating breathing‐like mechanics, was essential for in vitro modeling of the clinically relevant outcome of epithelial barrier disruption upon TNFα/IFNγ‐induced inflammation. |
| format | Article |
| id | doaj-art-306eeea721b44493b9ea312ec3c0ba22 |
| institution | Kabale University |
| issn | 2380-6761 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj-art-306eeea721b44493b9ea312ec3c0ba222025-01-09T06:19:46ZengWileyBioengineering & Translational Medicine2380-67612025-01-01101n/an/a10.1002/btm2.10715A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug responseClémentine Richter0Lorenz Latta1Daria Harig2Patrick Carius3Janick D. Stucki4Nina Hobi5Andreas Hugi6Paul Schumacher7Tobias Krebs8Alexander Gamrekeli9Felix Stöckle10Klaus Urbschat11Galia Montalvo12Franziska Lautenschläger13Brigitta Loretz14Alberto Hidalgo15Nicole Schneider‐Daum16Claus‐Michael Lehr17Helmholtz Institute for Pharmaceutical Research Saarland Saarbrücken GermanyHelmholtz Institute for Pharmaceutical Research Saarland Saarbrücken GermanyHelmholtz Institute for Pharmaceutical Research Saarland Saarbrücken GermanyHelmholtz Institute for Pharmaceutical Research Saarland Saarbrücken GermanyAlveoliX AG, Swiss Organs‐on‐Chip Innovation Bern SwitzerlandAlveoliX AG, Swiss Organs‐on‐Chip Innovation Bern SwitzerlandAlveoliX AG, Swiss Organs‐on‐Chip Innovation Bern SwitzerlandVitrocell® Systems GmbH Waldkirch GermanyVitrocell® Systems GmbH Waldkirch GermanyCenter for Thorax Medicine, Clinic Saarbrücken Saarbrücken GermanyCenter for Thorax Medicine, Clinic Saarbrücken Saarbrücken GermanySection of Thoracic Surgery of the Saar Lung Center, SHG Clinics Völklingen GermanyDepartment of Experimental Physics Saarland University Saarbrücken GermanyDepartment of Experimental Physics Saarland University Saarbrücken GermanyHelmholtz Institute for Pharmaceutical Research Saarland Saarbrücken GermanyHelmholtz Institute for Pharmaceutical Research Saarland Saarbrücken GermanyHelmholtz Institute for Pharmaceutical Research Saarland Saarbrücken GermanyHelmholtz Institute for Pharmaceutical Research Saarland Saarbrücken GermanyAbstract This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre‐clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co‐cultured with macrophages differentiated from the THP‐1 cell line, creating a physiological biological microenvironment. To mimic the three‐dimensional architecture and dynamic expansion and relaxation of the air‐blood‐barrier, they are grown on a stretchable microphysiological lung‐on‐chip. For validating the in vitro model, three different protocols have been developed to demonstrate the clinically established anti‐inflammatory effect of glucocorticoids to reduce certain inflammatory markers after different pro‐inflammatory stimuli: (1) an inflammation caused by bacterial LPS (lipopolysaccharides) to simulate an LPS‐induced acute lung injury measured best with cytokine IL‐6 release; (2) an inflammation caused by LPS at ALI (air‐liquid interface) to investigate aerosolized anti‐inflammatory treatment, measured with chemokine IL‐8 release; and (3) an inflammation with a combination of human inflammatory cytokines TNFα and IFNγ to simulate a critical cytokine storm leading to epithelial barrier disruption, where the eventual weakening or protection of the epithelial barrier can be measured. In all cases, the presence of macrophages appeared to be crucial to mediating inflammatory changes in the alveolar epithelium. LPS induction led to inflammatory changes independently of stretch conditions. Dynamic stretch, emulating breathing‐like mechanics, was essential for in vitro modeling of the clinically relevant outcome of epithelial barrier disruption upon TNFα/IFNγ‐induced inflammation.https://doi.org/10.1002/btm2.107153Racute lung injuryaerosolizationcytokine stormimmuno‐competentlung‐on‐chip |
| spellingShingle | Clémentine Richter Lorenz Latta Daria Harig Patrick Carius Janick D. Stucki Nina Hobi Andreas Hugi Paul Schumacher Tobias Krebs Alexander Gamrekeli Felix Stöckle Klaus Urbschat Galia Montalvo Franziska Lautenschläger Brigitta Loretz Alberto Hidalgo Nicole Schneider‐Daum Claus‐Michael Lehr A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response Bioengineering & Translational Medicine 3R acute lung injury aerosolization cytokine storm immuno‐competent lung‐on‐chip |
| title | A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response |
| title_full | A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response |
| title_fullStr | A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response |
| title_full_unstemmed | A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response |
| title_short | A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response |
| title_sort | stretchable human lung on chip model of alveolar inflammation for evaluating anti inflammatory drug response |
| topic | 3R acute lung injury aerosolization cytokine storm immuno‐competent lung‐on‐chip |
| url | https://doi.org/10.1002/btm2.10715 |
| work_keys_str_mv | AT clementinerichter astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT lorenzlatta astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT dariaharig astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT patrickcarius astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT janickdstucki astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT ninahobi astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT andreashugi astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT paulschumacher astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT tobiaskrebs astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT alexandergamrekeli astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT felixstockle astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT klausurbschat astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT galiamontalvo astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT franziskalautenschlager astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT brigittaloretz astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT albertohidalgo astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT nicoleschneiderdaum astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT clausmichaellehr astretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT clementinerichter stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT lorenzlatta stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT dariaharig stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT patrickcarius stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT janickdstucki stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT ninahobi stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT andreashugi stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT paulschumacher stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT tobiaskrebs stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT alexandergamrekeli stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT felixstockle stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT klausurbschat stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT galiamontalvo stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT franziskalautenschlager stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT brigittaloretz stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT albertohidalgo stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT nicoleschneiderdaum stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse AT clausmichaellehr stretchablehumanlungonchipmodelofalveolarinflammationforevaluatingantiinflammatorydrugresponse |