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hLMSC Secretome Affects Macrophage Activity Differentially Depending on Lung-Mimetic Environments

Falcones, Bryan LU orcid ; Söderlund, Zackarias LU orcid ; Ibáñez-Fonseca, Arturo LU orcid ; Almendros, Isaac ; Otero, Jordi ; Farré, Ramon ; Rolandsson Enes, Sara LU orcid ; Elowsson Rendin, Linda LU and Westergren-Thorsson, Gunilla LU orcid (2022) In Cells 11(12).
Abstract

Mesenchymal stromal cell (MSC)-based therapies for inflammatory diseases rely mainly on the paracrine ability to modulate the activity of macrophages. Despite recent advances, there is scarce information regarding changes of the secretome content attributed to physiomimetic cultures and, especially, how secretome content influence on macrophage activity for therapy. hLMSCs from human donors were cultured on devices developed in house that enabled lung-mimetic strain. hLMSC secretome was analyzed for typical cytokines, chemokines and growth factors. RNA was analyzed for the gene expression of CTGF and CYR61. Human monocytes were differentiated to macrophages and assessed for their phagocytic capacity and for M1/M2 subtypes by the... (More)

Mesenchymal stromal cell (MSC)-based therapies for inflammatory diseases rely mainly on the paracrine ability to modulate the activity of macrophages. Despite recent advances, there is scarce information regarding changes of the secretome content attributed to physiomimetic cultures and, especially, how secretome content influence on macrophage activity for therapy. hLMSCs from human donors were cultured on devices developed in house that enabled lung-mimetic strain. hLMSC secretome was analyzed for typical cytokines, chemokines and growth factors. RNA was analyzed for the gene expression of CTGF and CYR61. Human monocytes were differentiated to macrophages and assessed for their phagocytic capacity and for M1/M2 subtypes by the analysis of typical cell surface markers in the presence of hLMSC secretome. CTGF and CYR61 displayed a marked reduction when cultured in lung-derived hydrogels (L-Hydrogels). The secretome showed that lung-derived scaffolds had a distinct secretion while there was a large overlap between L-Hydrogel and the conventionally (2D) cultured samples. Additionally, secretome from L-Scaffold showed an HGF increase, while IL-6 and TNF-α decreased in lung-mimetic environments. Similarly, phagocytosis decreased in a lung-mimetic environment. L-Scaffold showed a decrease of M1 population while stretch upregulated M2b subpopulations. In summary, mechanical features of the lung ECM and stretch orchestrate anti-inflammatory and immunosuppressive outcomes of hLMSCs.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Hydrogels, Lung, Macrophages/metabolism, Mesenchymal Stem Cells/metabolism, Secretome
in
Cells
volume
11
issue
12
article number
1866
publisher
MDPI AG
external identifiers
  • pmid:35740995
  • scopus:85131437767
ISSN
2073-4409
DOI
10.3390/cells11121866
language
English
LU publication?
yes
id
d319e3c0-4c23-4e6d-84ea-4856e1901bed
date added to LUP
2022-08-31 14:44:45
date last changed
2024-06-10 04:48:24
@article{d319e3c0-4c23-4e6d-84ea-4856e1901bed,
  abstract     = {{<p>Mesenchymal stromal cell (MSC)-based therapies for inflammatory diseases rely mainly on the paracrine ability to modulate the activity of macrophages. Despite recent advances, there is scarce information regarding changes of the secretome content attributed to physiomimetic cultures and, especially, how secretome content influence on macrophage activity for therapy. hLMSCs from human donors were cultured on devices developed in house that enabled lung-mimetic strain. hLMSC secretome was analyzed for typical cytokines, chemokines and growth factors. RNA was analyzed for the gene expression of CTGF and CYR61. Human monocytes were differentiated to macrophages and assessed for their phagocytic capacity and for M1/M2 subtypes by the analysis of typical cell surface markers in the presence of hLMSC secretome. CTGF and CYR61 displayed a marked reduction when cultured in lung-derived hydrogels (L-Hydrogels). The secretome showed that lung-derived scaffolds had a distinct secretion while there was a large overlap between L-Hydrogel and the conventionally (2D) cultured samples. Additionally, secretome from L-Scaffold showed an HGF increase, while IL-6 and TNF-α decreased in lung-mimetic environments. Similarly, phagocytosis decreased in a lung-mimetic environment. L-Scaffold showed a decrease of M1 population while stretch upregulated M2b subpopulations. In summary, mechanical features of the lung ECM and stretch orchestrate anti-inflammatory and immunosuppressive outcomes of hLMSCs.</p>}},
  author       = {{Falcones, Bryan and Söderlund, Zackarias and Ibáñez-Fonseca, Arturo and Almendros, Isaac and Otero, Jordi and Farré, Ramon and Rolandsson Enes, Sara and Elowsson Rendin, Linda and Westergren-Thorsson, Gunilla}},
  issn         = {{2073-4409}},
  keywords     = {{Humans; Hydrogels; Lung; Macrophages/metabolism; Mesenchymal Stem Cells/metabolism; Secretome}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{hLMSC Secretome Affects Macrophage Activity Differentially Depending on Lung-Mimetic Environments}},
  url          = {{http://dx.doi.org/10.3390/cells11121866}},
  doi          = {{10.3390/cells11121866}},
  volume       = {{11}},
  year         = {{2022}},
}