Biowire Model of Interstitial and Focal Cardiac Fibrosis.

Autor:	Wang EY; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada., Rafatian N; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.; Toronto General Research Institute, Toronto, Ontario M5G 2C4, Canada., Zhao Y; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada., Lee A; RDM Division of Cardiovascular Medicine and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom., Lai BFL; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada., Lu RX; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada., Jekic D; McGill University, Montreal, Quebec H3A 2K6, Canada., Davenport Huyer L; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada., Knee-Walden EJ; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada., Bhattacharya S; RDM Division of Cardiovascular Medicine and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom., Backx PH; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.; Toronto General Research Institute, Toronto, Ontario M5G 2C4, Canada.; Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada., Radisic M; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.; Toronto General Research Institute, Toronto, Ontario M5G 2C4, Canada.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
Jazyk:	angličtina
Zdroj:	ACS central science [ACS Cent Sci] 2019 Jul 24; Vol. 5 (7), pp. 1146-1158. Date of Electronic Publication: 2019 Jun 04.
DOI:	10.1021/acscentsci.9b00052
Abstrakt:	Myocardial fibrosis is a severe global health problem due to its prevalence in all forms of cardiac diseases and direct role in causing heart failure. The discovery of efficient antifibrotic compounds has been hampered due to the lack of a physiologically relevant disease model. Herein, we present a disease model of human myocardial fibrosis and use it to establish a compound screening system. In the Biowire II platform, cardiac tissues are suspended between a pair of poly(octamethylene maleate (anhydride) citrate) (POMaC) wires. Noninvasive functional readouts are realized on the basis of the deflection of the intrinsically fluorescent polymer. The disease model is constructed to recapitulate contractile, biomechanical, and electrophysiological complexities of fibrotic myocardium. Additionally, we constructed a heteropolar integrated model with fibrotic and healthy cardiac tissues coupled together. The integrated model captures the regional heterogeneity of scar lesion, border zone, and adjacent healthy myocardium. Finally, we demonstrate the utility of the system for the evaluation of antifibrotic compounds. The high-fidelity in vitro model system combined with convenient functional readouts could potentially facilitate the development of precision medicine strategies for cardiac fibrosis modeling and establish a pipeline for preclinical compound screening. Competing Interests: The authors declare the following competing financial interest(s): Y.Z. and M.R. are co-founders of TARA Biosystems Inc. and hold equity in this company. TARA Biosystems Inc. uses the Biowire II technology described in this manuscript for commercial applications. All other authors have no conflicts of interest.
Databáze:	MEDLINE
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