Human cardiac fibroblasts adaptive responses to controlled combined mechanical strain and oxygen changes in vitro
Author(s)Ugolini, Giovanni Stefano; Pavesi, Andrea; Rasponi, Marco; Fiore, Gianfranco Beniamino; Soncini, Monica; Kamm, Roger Dale; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering
eLife Sciences Publications, Ltd.
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
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