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Quantifying extracellular matrix turnover in human lung scaffold cultures

Rosmark, Oskar LU ; Åhrman, Emma LU ; Müller, Catharina LU ; Elowsson Rendin, Linda LU ; Eriksson, Leif LU ; Malmström, Anders LU ; Hallgren, Oskar LU ; Larsson-Callerfelt, Anna Karin LU ; Westergren-Thorsson, Gunilla LU and Malmström, Johan LU (2018) In Scientific Reports 8(1).
Abstract

Remodelling of the extracellular matrix is accomplished by altering the balance between matrix macromolecule production and degradation. However, it is not well understood how cells balance production of new matrix molecules and degradation of existing ones during tissue remodelling and regeneration. In this study, we used decellularized lung scaffolds repopulated with allogenic lung fibroblasts cultured with stable isotope labelled amino acids to quantify the balance between matrix production and degradation at a proteome-wide scale. Specific temporal dynamics of different matrisome proteins were found to correspond to the proliferative activity of the repopulating cells and the degree of extracellular deposition. The remodeling of the... (More)

Remodelling of the extracellular matrix is accomplished by altering the balance between matrix macromolecule production and degradation. However, it is not well understood how cells balance production of new matrix molecules and degradation of existing ones during tissue remodelling and regeneration. In this study, we used decellularized lung scaffolds repopulated with allogenic lung fibroblasts cultured with stable isotope labelled amino acids to quantify the balance between matrix production and degradation at a proteome-wide scale. Specific temporal dynamics of different matrisome proteins were found to correspond to the proliferative activity of the repopulating cells and the degree of extracellular deposition. The remodeling of the scaffold was characterized by an initial phase with cell proliferation and high production of cell adhesion proteins such as emilin-1 and fibronectin. Extended culture time resulted in increased levels of core matrisome proteins. In a comparison with monolayer cultures on plastic, culture in lung scaffolds lead to a pronounced accumulation of proteoglycans, such as versican and decorin, resulting in regeneration of an extracellular matrix with greater resemblance to native lung tissue compared to standard monolayer cultures. Collectively, the study presents a promising technique for increasing the understanding of cell- extracellular matrix interactions under healthy and diseased conditions.

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publication status
published
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in
Scientific Reports
volume
8
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85044953122
ISSN
2045-2322
DOI
10.1038/s41598-018-23702-x
language
English
LU publication?
yes
id
7676945c-728e-4e6e-b460-d1677b24934b
date added to LUP
2018-04-16 15:09:35
date last changed
2018-05-29 11:24:58
@article{7676945c-728e-4e6e-b460-d1677b24934b,
  abstract     = {<p>Remodelling of the extracellular matrix is accomplished by altering the balance between matrix macromolecule production and degradation. However, it is not well understood how cells balance production of new matrix molecules and degradation of existing ones during tissue remodelling and regeneration. In this study, we used decellularized lung scaffolds repopulated with allogenic lung fibroblasts cultured with stable isotope labelled amino acids to quantify the balance between matrix production and degradation at a proteome-wide scale. Specific temporal dynamics of different matrisome proteins were found to correspond to the proliferative activity of the repopulating cells and the degree of extracellular deposition. The remodeling of the scaffold was characterized by an initial phase with cell proliferation and high production of cell adhesion proteins such as emilin-1 and fibronectin. Extended culture time resulted in increased levels of core matrisome proteins. In a comparison with monolayer cultures on plastic, culture in lung scaffolds lead to a pronounced accumulation of proteoglycans, such as versican and decorin, resulting in regeneration of an extracellular matrix with greater resemblance to native lung tissue compared to standard monolayer cultures. Collectively, the study presents a promising technique for increasing the understanding of cell- extracellular matrix interactions under healthy and diseased conditions.</p>},
  articleno    = {5409},
  author       = {Rosmark, Oskar and Åhrman, Emma and Müller, Catharina and Elowsson Rendin, Linda and Eriksson, Leif and Malmström, Anders and Hallgren, Oskar and Larsson-Callerfelt, Anna Karin and Westergren-Thorsson, Gunilla and Malmström, Johan},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Quantifying extracellular matrix turnover in human lung scaffold cultures},
  url          = {http://dx.doi.org/10.1038/s41598-018-23702-x},
  volume       = {8},
  year         = {2018},
}