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Mesenchymal Stromal Cells and Their Extracellular Vesicles Enhance the Anti-Inflammatory Phenotype of Regulatory Macrophages by Downregulating the Production of Interleukin (IL)-23 and IL-22
Open accessAbstract
Resolution-phase macrophage population orchestrates active dampening of the inflammation by secreting anti-inflammatory and proresolving products including interleukin (IL)-10 and lipid mediators. We investigated the effects of both human bone marrow-derived mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) on mature human regulatory macrophages (Mregs). The cytokines and lipid mediators were determined from cell culture media of Mregs cultivated with MSCs and MSC-EVs. Additionally, the alterations in the expression of cell surface markers and the phagocytic ability of Mregs were investigated. Our novel findings indicate that both MSC co-culture and MSC-EVs down-regulated the production of IL-23 and IL-22 enhancing the anti-inflammatory phenotype of Mregs and amplifying proresolving properties. The levels of prostaglandin E2 (PGE2) were substantially upregulated in MSC co-culture media, which may endorse proresolving lipid mediator class switching. Additionally, our results manifest, for the first time, that MSC-EVs mediate the Mreg phenotype change via PGE2. These data suggest that both human MSC and MSC-EVs may potentiate tolerance-promoting proresolving phenotype of human Mregs.
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“The authors also demonstrated that MSC-EVs mediate their action, at least in part, via PGE2 (Table 1) [75].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [75]
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“Hyvarinen and co-workers have shown that BM-MSCs co-culture with regulatory macrophages and MSC-EVs decrease the levels of IL-22 and IL-23 in the macrophages-produced CM [75].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [75]
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Metadata
- Authors
- Hyvärinen, K., Holopainen, M., Skirdenko, V., Ruhanen, H., Lehenkari, P., Korhonen, M., Käkelä, R., Laitinen, S., & Kerkelä, E.
- Affiliations
- Finnish Red Cross (FI)
- University of Helsinki (FI)
- Oulu University Hospital (FI)
- Corresponding author
- Hyvärinen, Kati
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2018-04-12
- Volume
- 9
- Pages
- 771-771
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5906545
- OpenAlex
- W2797721539
- Cited by
- 111
- References
- 58
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 17 · 2023: 19 · 2022: 17 · 2021: 17 · 2020: 20 · 2019: 4 · 2018: 5
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Tekes (3986/31/2013)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- mesenchymal stem cells, extracellular vesicles, regulatory macrophages, IL-23, IL-22, prostaglandin E2, inflammation resolution, specialized pro-resolving mediators, phagocytosis, cell surface markers, bone marrow-derived cells
- MeSH terms
- Extracellular Vesicles, Interleukin-22, Humans, Immune Tolerance, Inflammation, Interleukins, Macrophages, Phenotype, Down-Regulation, Interleukin-23, Mesenchymal Stem Cells
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