Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing. (March 2020)

• Record Type: Journal Article
• Authors: Mastikhina, Olya; Moon, Byeong-Ui; Williams, Kenneth; Hatkar, Rupal; Gustafson, Dakota; Mourad, Omar; Sun, Xuetao; Koo, Margaret; Lam, Alan Y.L.; Sun, Yu; Fish, Jason E.; Young, Edmond W.K.; Nunes, Sara S.
• Is Part Of: Biomaterials. Volume 233(2020)
• Publication Date: 2020-03
• Subjects: Organ-on-a-chip -- Tissue engineering -- Heart failure -- Cardiac fibrosis -- Human stem cell-derived cardiomyocytes -- Disease modeling -- Pirfenidone -- Carvediolol -- Losartan -- Force of contraction -- microRNA -- Extracellular vesicles; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2019.119741
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure in vitro, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function. Graphical abstract: Image 1