RT Journal Article
SR Electronic
T1 Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug screening
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 632406
DO 10.1101/632406
A1 Olya Mastikhina
A1 Byeong-Ui Moon
A1 Kenneth Williams
A1 Rupal Hatkar
A1 Dakota Gustafson
A1 Xuetao Sun
A1 Margaret Koo
A1 Alan Y.L. Lam
A1 Yu Sun
A1 Jason E. Fish
A1 Edmond W.K. Young
A1 Sara S. Nunes
YR 2019
UL http://biorxiv.org/content/early/2019/08/14/632406.abstract
AB 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.