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. Singapore-MIT Alliance for Research and Technology, Singapore

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

    Biosym IRG, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore
    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.

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.

Metrics

  • 2,922
    views
  • 490
    downloads
  • 39
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.22847

Further reading

    1. Medicine
    2. Neuroscience
    Tomohiro Umeda, Ayumi Sakai ... Takami Tomiyama
    Research Article

    Neurodegenerative diseases are age-related disorders characterized by the cerebral accumulation of amyloidogenic proteins, and cellular senescence underlies their pathogenesis. Thus, it is necessary for preventing these diseases to remove toxic proteins, repair damaged neurons, and suppress cellular senescence. As a source for such prophylactic agents, we selected zizyphi spinosi semen (ZSS), a medicinal herb used in traditional Chinese medicine. Oral administration of ZSS hot water extract ameliorated Aβ and tau pathology and cognitive impairment in mouse models of Alzheimer’s disease and frontotemporal dementia. Non-extracted ZSS simple crush powder showed stronger effects than the extract and improved α-synuclein pathology and cognitive/motor function in Parkinson’s disease model mice. Furthermore, when administered to normal aged mice, the ZSS powder suppressed cellular senescence, reduced DNA oxidation, promoted brain-derived neurotrophic factor expression and neurogenesis, and enhanced cognition to levels similar to those in young mice. The quantity of known active ingredients of ZSS, jujuboside A, jujuboside B, and spinosin was not proportional to the nootropic activity of ZSS. These results suggest that ZSS simple crush powder is a promising dietary material for the prevention of neurodegenerative diseases and brain aging.

    1. Medicine
    Hyun Beom Song, Laura Campello ... Anand Swaroop
    Research Advance

    Inherited retinal degenerations (IRDs) constitute a group of clinically and genetically diverse vision-impairing disorders. Retinitis pigmentosa (RP), the most common form of IRD, is characterized by gradual dysfunction and degeneration of rod photoreceptors, followed by the loss of cone photoreceptors. Recently, we identified reserpine as a lead molecule for maintaining rod survival in mouse and human retinal organoids as well as in the rd16 mouse, which phenocopy Leber congenital amaurosis caused by mutations in the cilia-centrosomal gene CEP290 (Chen et al., 2023). Here, we show the therapeutic potential of reserpine in a rhodopsin P23H rat model of autosomal dominant RP. At postnatal day (P) 68, when males and females are analyzed together, the reserpine-treated rats exhibit higher rod-derived scotopic b-wave amplitudes compared to the controls with little or no change in scotopic a-wave or cone-derived photopic b-wave. Interestingly, the reserpine-treated female rats display enhanced scotopic a- and b-waves and photopic b-wave responses at P68, along with a better contrast threshold and increased outer nuclear layer thickness. The female rats demonstrate better preservation of both rod and cone photoreceptors following reserpine treatment. Retinal transcriptome analysis reveals sex-specific responses to reserpine, with significant upregulation of phototransduction genes and proteostasis-related pathways, and notably, genes associated with stress response. This study builds upon our previously reported results reaffirming the potential of reserpine for gene-agnostic treatment of IRDs and emphasizes the importance of biological sex in retinal disease research and therapy development.