Journal
CELLS
Volume 11, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/cells11121866
Keywords
MSC-based therapy; lung physiomimetic culture; preconditioning; macrophages
Categories
Funding
- Swedish Heart Lung foundation [20210086, 20200122, 20180660]
- Swedish Research Council [01190, 01375]
- Swedish Foundation for Strategic Research [SBE13-0130]
- Lund University Medical Faculty
- Ake and Inger Bergkvist foundation
- Royal Physiographic Society of Lund [40451]
- Spanish Ministry of Sciences Innovation and Universities [PID2020-113910RB-I00-AEI/10.13039/501100011033]
- Fundacion Ramon Areces (Spain) [BEVP33S12276]
- ALF project [0097]
- Swedish Foundation for Strategic Research (SSF) [SBE13-0130] Funding Source: Swedish Foundation for Strategic Research (SSF)
- Swedish Heart-Lung Foundation [20180660, 20200122, 20210086] Funding Source: Swedish Heart-Lung Foundation
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MSC-based therapies for inflammatory diseases rely on their paracrine ability to modulate macrophage activity. This study found that physiomimetic cultures can alter the secretome of MSCs and influence macrophage activity. Lung-derived hydrogels showed different secretions compared to conventionally cultured samples, and secretome from lung-mimetic environments resulted in decreased phagocytic capacity and M1 subtype of macrophages.
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-alpha 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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