Human cardiac fibroblasts adaptive responses to controlled combined mechanical strain and oxygen changes in vitro
Name
Ugolini-2017-Human cardiac fibroblasts adaptiv.pdf
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3.94 MB
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Adobe PDF
Checksum (MD5)
c330098f0b5a815f143b4b4d90203ce7
Author(s)
Ugolini, Giovanni Stefano
Pavesi, Andrea
Rasponi, Marco
Fiore, Gianfranco Beniamino
Soncini, Monica
Kamm, Roger Dale
Date Issued
March 2017
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Ugolini, Giovanni Stefano; Pavesi, Andrea; Rasponi, Marco; Fiore, Gianfranco Beniamino; Kamm, Roger and Soncini, Monica. “Human Cardiac Fibroblasts Adaptive Responses to Controlled Combined Mechanical Strain and Oxygen Changes in Vitro.” eLife 6 (March 2017): e22847 © 2017 Ugolini et al
Version
Final published version
Abstract
Upon cardiac pathological conditions such as ischemia, microenvironmental changes instruct a series of cellular responses that trigger cardiac fibroblasts-mediated tissue adaptation and inflammation. A comprehensive model of how early environmental changes may induce cardiac fibroblasts (CF) pathological responses is far from being elucidated, partly due to the lack of approaches involving complex and simultaneous environmental stimulation. Here, we provide a first analysis of human primary CF behavior by means of a multi-stimulus microdevice for combined application of cyclic mechanical strain and controlled oxygen tension. Our findings elucidate differential human CFs responses to different combinations of the above stimuli. Individual stimuli cause proliferative effects (PHH3+ mitotic cells, YAP translocation, PDGF secretion) or increase collagen presence. Interestingly, only the combination of hypoxia and a simulated loss of contractility (2% strain) is able to additionally induce increased CF release of inflammatory and pro-fibrotic cytokines and matrix metalloproteinases.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.7554/eLife.22847
