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Open AccessArticle

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

1
Finnish Red Cross Blood Service, FI-00310 Helsinki, Finland
2
Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, FI-00014 Helsinki, Finland
3
Department of Anatomy and Surgery, Institute of Translational Medicine, University of Oulu and Clinical Research Centre, FI-90014 Oulu, Finland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Cells 2020, 9(9), 2142; https://doi.org/10.3390/cells9092142
Received: 31 August 2020 / Revised: 18 September 2020 / Accepted: 21 September 2020 / Published: 22 September 2020
(This article belongs to the Special Issue Enhancing Mesenchymal Stem Cells (MSCs) for Therapeutic Purposes)
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 improved Candida albicans phagocytosis 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. View Full-Text
Keywords: cell therapy; immunomodulation; polyunsaturated fatty acid; CD206; phagocytosis cell therapy; immunomodulation; polyunsaturated fatty acid; CD206; phagocytosis
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Holopainen, M.; Impola, U.; Lehenkari, P.; Laitinen, S.; Kerkelä, E. Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages. Cells 2020, 9, 2142.

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