Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis

Frontiers in Cardiovascular Medicine

article

Thomas C. L. Bracco Gartner¹  Sandra Crnko²  Laurynas Leiteris²  Iris van Adrichem²  Linda W. van Laake²  Carlijn V. C. Bouten⁴  Marie José Goumans⁶  Willem J. L. Suyker¹  Joost P. G. Sluijter²  Jesper Hjortnaes¹ 

[1] Department of Cardiothoracic Surgery, University Medical Center Utrecht;Regenerative Medicine Center Utrecht, Circulatory Health Laboratory;Experimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht;Department of Biomedical Technology, Eindhoven University of Technology;Institute for Complex Molecular Systems ,(ICMS), Eindhoven University of Technology;Department of Cell and Chemical Biology, Leiden University Medical Center;Utrecht University

关键词: cardiac fibrosis;    tissue-engineering;    disease modeling;    pirfenidone;    targeted proteomics;    3D cell culture;   

DOI  :  10.3389/fcvm.2022.854314

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY