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
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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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MSC-EVs mediate their action at least in part via PGE2.
“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]
The Results (Table 3) show increased PGE2 in Mreg-conditioned media exposed to MSC-EVs, and the Introduction says MSC-EVs may mediate the observed cytokine changes via PGE2. The Discussion says this mechanism requires further study, so the paper does not demonstrate that EV action occurs via PGE2. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBM-MSCs co-cultured with regulatory macrophages and MSC-EVs decrease the levels of IL-22 and IL-23 in macrophage-produced conditioned media.
“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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- 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
- Health Sciences › Medicine › Genetics › 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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