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Late Breaking Abstract - IPF lung-ECM subjected to cyclic stretch affect cellular activity

Bryan Falcones Olarte, Linda Elowsson Rendin, Anna Löfdahl, Isaac Almendros Lopez, Jorge Otero, Xiao-Hong Zhou, Martin Silverborn, Leif Bjermer, Göran Dellgren, Ramon Farré, Gunilla Westergren-Thorsson
European Respiratory Journal 2020 56: 4320; DOI: 10.1183/13993003.congress-2020.4320
Bryan Falcones Olarte
1Unit of Biophysics and Bioengineering, Universitat Autonoma de Barcelona, Barcelona, Spain
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  • For correspondence: bryan.falcones_olarte@med.lu.se
Linda Elowsson Rendin
2Lung Biology, Lund University, Lund, Sweden
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Anna Löfdahl
2Lung Biology, Lund University, Lund, Sweden
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Isaac Almendros Lopez
1Unit of Biophysics and Bioengineering, Universitat Autonoma de Barcelona, Barcelona, Spain
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Jorge Otero
1Unit of Biophysics and Bioengineering, Universitat Autonoma de Barcelona, Barcelona, Spain
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Xiao-Hong Zhou
3Bioscience Department, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden
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Martin Silverborn
4Department of Cardiothoracic Surgery and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
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Leif Bjermer
5Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden
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Göran Dellgren
4Department of Cardiothoracic Surgery and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
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Ramon Farré
1Unit of Biophysics and Bioengineering, Universitat Autonoma de Barcelona, Barcelona, Spain
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Gunilla Westergren-Thorsson
2Lung Biology, Lund University, Lund, Sweden
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Abstract

Introduction: Idiopathic pulmonary fibrosis (IPF) involves extensive remodeling of the extracellular matrix (ECM), primarily in the periphery of the lung. This leads to altered mechanical properties, which in turn results in altered mechanical stimulation of the cells. In stiffer and less elastic ECM found in IPF, fibroblasts are thus exposed to altered strain compared to a healthy ECM. Our aim is to investigate the impact of mechanical stimulation on fibroblasts activity in IPF.

Methods: IPF and healthy distal lung tissue were decellularized in slices (350 mm) to produce acellular lung scaffolds. The scaffolds were attached to a custom-made device for cyclic stretch built in polydimethylsiloxane and repopulated with healthy primary distal lung fibroblasts. The scaffolds were either exposed to cyclic stretch (0.2 Hz, 10% strain) or cultured under static conditions upto 3 days and analyzed for cell viability, histology, RNA expression, and released mediators.

Results: Compared to healthy scaffolds, fibroblasts on IPF scaffolds showed increased metabolic activity, both at static and cyclic stretch condition. Scaffolds under cyclic stretch showed preserved tissue morphology with dispersed elongated fibroblasts shown with H&E staining. Interestingly, we see a shift in released mediators linked to angiogenesis in cyclic stretch cultures, mostly pronounced in IPF scaffolds.

Discussion: We demonstrate that we have developed a physiological more relevant ex vivo model to study cellular responses in lung tissue. Our data indicate that there is a change in cellular activity in IPF tissue under cyclic stretch. This allows us to study the effect of alterations in mechanical and matrisome properties in chronic lung disease.

  • Idiopathic pulmonary fibrosis
  • Morphology

Footnotes

Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4320.

This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2020
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Late Breaking Abstract - IPF lung-ECM subjected to cyclic stretch affect cellular activity
Bryan Falcones Olarte, Linda Elowsson Rendin, Anna Löfdahl, Isaac Almendros Lopez, Jorge Otero, Xiao-Hong Zhou, Martin Silverborn, Leif Bjermer, Göran Dellgren, Ramon Farré, Gunilla Westergren-Thorsson
European Respiratory Journal Sep 2020, 56 (suppl 64) 4320; DOI: 10.1183/13993003.congress-2020.4320

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Late Breaking Abstract - IPF lung-ECM subjected to cyclic stretch affect cellular activity
Bryan Falcones Olarte, Linda Elowsson Rendin, Anna Löfdahl, Isaac Almendros Lopez, Jorge Otero, Xiao-Hong Zhou, Martin Silverborn, Leif Bjermer, Göran Dellgren, Ramon Farré, Gunilla Westergren-Thorsson
European Respiratory Journal Sep 2020, 56 (suppl 64) 4320; DOI: 10.1183/13993003.congress-2020.4320
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