Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis
A fundamental process in the development and progression of heart failure is fibrotic remodeling, characterized by excessive deposition of extracellular matrix proteins in response to injury. Currently, therapies that effectively target and reverse cardiac fibrosis are lacking, warranting novel ther...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.854314/full |
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| author | Thomas C. L. Bracco Gartner Thomas C. L. Bracco Gartner Thomas C. L. Bracco Gartner Sandra Crnko Sandra Crnko Laurynas Leiteris Iris van Adrichem Linda W. van Laake Linda W. van Laake Carlijn V. C. Bouten Carlijn V. C. Bouten Marie José Goumans Willem J. L. Suyker Willem J. L. Suyker Willem J. L. Suyker Joost P. G. Sluijter Joost P. G. Sluijter Joost P. G. Sluijter Jesper Hjortnaes Jesper Hjortnaes |
| author_facet | Thomas C. L. Bracco Gartner Thomas C. L. Bracco Gartner Thomas C. L. Bracco Gartner Sandra Crnko Sandra Crnko Laurynas Leiteris Iris van Adrichem Linda W. van Laake Linda W. van Laake Carlijn V. C. Bouten Carlijn V. C. Bouten Marie José Goumans Willem J. L. Suyker Willem J. L. Suyker Willem J. L. Suyker Joost P. G. Sluijter Joost P. G. Sluijter Joost P. G. Sluijter Jesper Hjortnaes Jesper Hjortnaes |
| author_sort | Thomas C. L. Bracco Gartner |
| collection | DOAJ |
| description | A fundamental process in the development and progression of heart failure is fibrotic remodeling, characterized by excessive deposition of extracellular matrix proteins in response to injury. Currently, therapies that effectively target and reverse cardiac fibrosis are lacking, warranting novel therapeutic strategies and reliable methods to study their effect. Using a gelatin methacryloyl hydrogel, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and human fetal cardiac fibroblasts (hfCF), we developed a multi-cellular mechanically tunable 3D in vitro model of human cardiac fibrosis. This model was used to evaluate the effects of a promising anti-fibrotic drug—pirfenidone—and yields proof-of-concept of the drug testing potential of this platform. Our study demonstrates that pirfenidone has anti-fibrotic effects but does not reverse all TGF-β1 induced pro-fibrotic changes, which provides new insights into its mechanism of action. |
| first_indexed | 2024-12-13T10:04:40Z |
| format | Article |
| id | doaj.art-9e7e4afc48db4fedbeafb5ecf7228b0f |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-13T10:04:40Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-9e7e4afc48db4fedbeafb5ecf7228b0f2022-12-21T23:51:34ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-03-01910.3389/fcvm.2022.854314854314Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac FibrosisThomas C. L. Bracco Gartner0Thomas C. L. Bracco Gartner1Thomas C. L. Bracco Gartner2Sandra Crnko3Sandra Crnko4Laurynas Leiteris5Iris van Adrichem6Linda W. van Laake7Linda W. van Laake8Carlijn V. C. Bouten9Carlijn V. C. Bouten10Marie José Goumans11Willem J. L. Suyker12Willem J. L. Suyker13Willem J. L. Suyker14Joost P. G. Sluijter15Joost P. G. Sluijter16Joost P. G. Sluijter17Jesper Hjortnaes18Jesper Hjortnaes19Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht, NetherlandsExperimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht, NetherlandsExperimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht, NetherlandsExperimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Biomedical Technology, Eindhoven University of Technology, Eindhoven, NetherlandsInstitute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht, NetherlandsUtrecht University, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht, NetherlandsExperimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, NetherlandsUtrecht University, Utrecht, NetherlandsDepartment of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht, NetherlandsA fundamental process in the development and progression of heart failure is fibrotic remodeling, characterized by excessive deposition of extracellular matrix proteins in response to injury. Currently, therapies that effectively target and reverse cardiac fibrosis are lacking, warranting novel therapeutic strategies and reliable methods to study their effect. Using a gelatin methacryloyl hydrogel, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and human fetal cardiac fibroblasts (hfCF), we developed a multi-cellular mechanically tunable 3D in vitro model of human cardiac fibrosis. This model was used to evaluate the effects of a promising anti-fibrotic drug—pirfenidone—and yields proof-of-concept of the drug testing potential of this platform. Our study demonstrates that pirfenidone has anti-fibrotic effects but does not reverse all TGF-β1 induced pro-fibrotic changes, which provides new insights into its mechanism of action.https://www.frontiersin.org/articles/10.3389/fcvm.2022.854314/fullcardiac fibrosistissue-engineeringdisease modelingpirfenidonetargeted proteomics3D cell culture |
| spellingShingle | Thomas C. L. Bracco Gartner Thomas C. L. Bracco Gartner Thomas C. L. Bracco Gartner Sandra Crnko Sandra Crnko Laurynas Leiteris Iris van Adrichem Linda W. van Laake Linda W. van Laake Carlijn V. C. Bouten Carlijn V. C. Bouten Marie José Goumans Willem J. L. Suyker Willem J. L. Suyker Willem J. L. Suyker Joost P. G. Sluijter Joost P. G. Sluijter Joost P. G. Sluijter Jesper Hjortnaes Jesper Hjortnaes Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis Frontiers in Cardiovascular Medicine cardiac fibrosis tissue-engineering disease modeling pirfenidone targeted proteomics 3D cell culture |
| title | Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis |
| title_full | Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis |
| title_fullStr | Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis |
| title_full_unstemmed | Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis |
| title_short | Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis |
| title_sort | pirfenidone has anti fibrotic effects in a tissue engineered model of human cardiac fibrosis |
| topic | cardiac fibrosis tissue-engineering disease modeling pirfenidone targeted proteomics 3D cell culture |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.854314/full |
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