Human cardiac fibroblasts adaptive responses to controlled combined mechanical strain and oxygen changes in vitro

  1. Giovanni Stefano Ugolini
  2. Andrea Pavesi
  3. Marco Rasponi
  4. Gianfranco Beniamino Fiore
  5. Roger Kamm
  6. Monica Soncini  Is a corresponding author
  1. Politecnico di Milano, Italy
  2. Agency for Science, Technology and Research, Singapore
  3. Massachusetts Institute of Technology, United States

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.

Article and author information

Author details

  1. Giovanni Stefano Ugolini

    Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Andrea Pavesi

    Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2777-1043
  3. Marco Rasponi

    Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Gianfranco Beniamino Fiore

    Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Roger Kamm

    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Monica Soncini

    Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy
    For correspondence
    monica.soncini@polimi.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8607-7196

Funding

No external funding was received for this work.

Reviewing Editor

  1. Gordana Vunjak-Novakovic, Columbia University, United States

Version history

  1. Received: November 8, 2016
  2. Accepted: March 17, 2017
  3. Accepted Manuscript published: March 18, 2017 (version 1)
  4. Accepted Manuscript updated: March 22, 2017 (version 2)
  5. Version of Record published: April 27, 2017 (version 3)

Copyright

© 2017, Ugolini et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Giovanni Stefano Ugolini
  2. Andrea Pavesi
  3. Marco Rasponi
  4. Gianfranco Beniamino Fiore
  5. Roger Kamm
  6. Monica Soncini
(2017)
Human cardiac fibroblasts adaptive responses to controlled combined mechanical strain and oxygen changes in vitro
eLife 6:e22847.
https://doi.org/10.7554/eLife.22847

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