hLMSC Secretome Affects Macrophage Activity Differentially Depending on Lung-Mimetic Environments
(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
- Falcones, Bryan LU ; Söderlund, Zackarias LU ; Ibáñez-Fonseca, Arturo LU ; Almendros, Isaac ; Otero, Jordi ; Farré, Ramon ; Rolandsson Enes, Sara LU ; Elowsson Rendin, Linda LU and Westergren-Thorsson, Gunilla LU
- organization
- publishing date
- 2022
- 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
-
- scopus:85131437767
- pmid:35740995
- 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
- 2024-09-16 13:57:08
@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}}, }