Cargando…
Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages
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 investigat...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564172/ https://www.ncbi.nlm.nih.gov/pubmed/32972000 http://dx.doi.org/10.3390/cells9092142 |
_version_ | 1783595652205248512 |
---|---|
author | Holopainen, Minna Impola, Ulla Lehenkari, Petri Laitinen, Saara Kerkelä, Erja |
author_facet | Holopainen, Minna Impola, Ulla Lehenkari, Petri Laitinen, Saara Kerkelä, Erja |
author_sort | Holopainen, Minna |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7564172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75641722020-10-26 Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages Holopainen, Minna Impola, Ulla Lehenkari, Petri Laitinen, Saara Kerkelä, Erja Cells Article 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. MDPI 2020-09-22 /pmc/articles/PMC7564172/ /pubmed/32972000 http://dx.doi.org/10.3390/cells9092142 Text en © 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/). |
spellingShingle | Article Holopainen, Minna Impola, Ulla Lehenkari, Petri Laitinen, Saara Kerkelä, Erja Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages |
title | Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages |
title_full | Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages |
title_fullStr | Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages |
title_full_unstemmed | Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages |
title_short | Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages |
title_sort | human mesenchymal stromal cell secretome promotes the immunoregulatory phenotype and phagocytosis activity in human macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564172/ https://www.ncbi.nlm.nih.gov/pubmed/32972000 http://dx.doi.org/10.3390/cells9092142 |
work_keys_str_mv | AT holopainenminna humanmesenchymalstromalcellsecretomepromotestheimmunoregulatoryphenotypeandphagocytosisactivityinhumanmacrophages AT impolaulla humanmesenchymalstromalcellsecretomepromotestheimmunoregulatoryphenotypeandphagocytosisactivityinhumanmacrophages AT lehenkaripetri humanmesenchymalstromalcellsecretomepromotestheimmunoregulatoryphenotypeandphagocytosisactivityinhumanmacrophages AT laitinensaara humanmesenchymalstromalcellsecretomepromotestheimmunoregulatoryphenotypeandphagocytosisactivityinhumanmacrophages AT kerkelaerja humanmesenchymalstromalcellsecretomepromotestheimmunoregulatoryphenotypeandphagocytosisactivityinhumanmacrophages |