Fibrotic microtissue array to predict anti-fibrosis drug efficacy

Mohammadnabi Asmani, Sanjana Velumani, Yan Li, Nicole Wawrzyniak, Isaac Hsia, Zhaowei Chen, Boris Hinz and Ruogang Zhao ()
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Mohammadnabi Asmani: The State University of New York
Sanjana Velumani: The State University of New York
Yan Li: The State University of New York
Nicole Wawrzyniak: The State University of New York
Isaac Hsia: The State University of New York
Zhaowei Chen: The State University of New York
Boris Hinz: University of Toronto
Ruogang Zhao: The State University of New York

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Fibrosis is a severe health problem characterized by progressive stiffening of tissues which causes organ malfunction and failure. A major bottleneck in developing new anti-fibrosis therapies is the lack of in vitro models that recapitulate dynamic changes in tissue mechanics during fibrogenesis. Here we create membranous human lung microtissues to model key biomechanical events occurred during lung fibrogenesis including progressive stiffening and contraction of alveolar tissue, decline in alveolar tissue compliance and traction force-induced bronchial dilation. With these capabilities, we provide proof of principle for using this fibrotic tissue array for multi-parameter, phenotypic analysis of the therapeutic efficacy of two anti-fibrosis drugs recently approved by the FDA. Preventative treatments with Pirfenidone and Nintedanib reduce tissue contractility and prevent tissue stiffening and decline in tissue compliance. In a therapeutic treatment regimen, both drugs restore tissue compliance. These results highlight the pathophysiologically relevant modeling capability of our novel fibrotic microtissue system.

Date: 2018
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DOI: 10.1038/s41467-018-04336-z

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