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. https://doi.org/10.3390/cells9092142
Human mesenchymal stromal cell secretome promotes the immunoregulatory phenotype and phagocytosis activity in human macrophages
|Author:||Holopainen, Minna1,2; Impola, Ulla1; Lehenkari, Petri3;|
1Finnish Red Cross Blood Service, FI-00310 Helsinki, Finland
2Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, FI-00014 Helsinki, Finland
3Department of Anatomy and Surgery, Institute of Translational Medicine, University of Oulu and Clinical Research Centre, FI-90014 Oulu, Finland
|Online Access:||PDF Full Text (PDF, 3.3 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202102083981
Multidisciplinary Digital Publishing Institute,
|Publish Date:|| 2021-02-08
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was supported by Finnish Cultural Foundation (M.H.) and Clinical State Research Funding [EVO/ VTR grant, Finland] (M.H.).
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).