Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages

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Holopainen , M , Impola , U , Lehenkari , P , Laitinen , S & Kerkela , E 2020 , ' Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages ' , Cells , vol. 9 , no. 9 , 2142 . https://doi.org/10.3390/cells9092142

Title: Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages
Author: Holopainen, Minna; Impola, Ulla; Lehenkari, Petri; Laitinen, Saara; Kerkela, Erja
Contributor: University of Helsinki, Functional Lipidomics Group
Date: 2020-09
Language: eng
Number of pages: 18
Belongs to series: Cells
ISSN: 2073-4409
URI: http://hdl.handle.net/10138/321255
Abstract: Human mesenchymal stromal/stem cells (hMSCs) show great promise in cell therapy due to their immunomodulatory properties. The overall immunomodulatory response of hMSCs resembles the resolution of inflammation, in which lipid mediators and regulatory macrophages (Mregs) play key roles. We investigated the effect of hMSC cell-cell contact and secretome on macrophages polarized and activated toward Mreg phenotype. Moreover, we studied the effect of supplemented polyunsaturated fatty acids (PUFAs): docosahexaenoic acid (DHA) and arachidonic acid, the precursors of lipid mediators, on hMSC immunomodulation. Our results show that unlike hMSC cell-cell contact, the hMSC secretome markedly increased the CD206 expression in both Mreg-polarized and Mreg-activated macrophages. Moreover, the secretome enhanced the expression of programmed death-ligand 1 on Mreg-polarized macrophages and Mer receptor tyrosine kinase on Mreg-activated macrophages. Remarkably, these changes were translated into improvedCandida albicansphagocytosis activity of macrophages. Taken together, these results demonstrate that the hMSC secretome promotes the immunoregulatory and proresolving phenotype of Mregs. Intriguingly, DHA supplementation to hMSCs resulted in a more potentiated immunomodulation with increased CD163 expression and decreased gene expression of matrix metalloproteinase 2 in Mreg-polarized macrophages. These findings highlight the potential of PUFA supplementations as an easy and safe method to improve the hMSC therapeutic potential.
Subject: cell therapy
immunomodulation
polyunsaturated fatty acid
CD206
phagocytosis
STEM-CELLS
EXTRACELLULAR VESICLES
REGULATORY MACROPHAGES
PERIANAL FISTULAS
APOPTOTIC CELLS
INFLAMMATION
MECHANISMS
THERAPY
INNATE
POLARIZATION
1184 Genetics, developmental biology, physiology
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