MSCs’ conditioned media cytokine and growth factor profiles and their impact on macrophage polarization
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Abstract
Background: There is a growing body of evidence that multipotent mesenchymal stromal cells’ (MSCs’) remarkable therapeutic potential is attributed not only to their differentiation and regenerative capacity, but also to the paracrine effect, underlying their immunomodulatory properties. MSCs’ secretome (i.e., cytokines, growth factors, and extracellular vesicles) is therefore increasingly discussed in the context of their ability to modulate inflammatory response and promote regeneration. There is evidence that 2D or 3D culturing conditions have an impact on the cells’ secretome, and here we aimed to compare the secretion of cytokines and growth factors in human MSCs from different sources cultured in 2D and 3D conditions and assess their effect on human macrophages polarization in vitro. Methods: MSCs were derived from human adipose tissue, bone marrow, gingiva, placenta, and umbilical cord, cultured as monolayers or as cell spheroids. Their cytokine profiles were analyzed, and data standardization was carried out using a z -score. Human peripheral blood mononuclear cells-derived macrophages were then treated with umbilical cord-derived MSCs’ conditioned media and their effect on macrophages polarization was assessed. Results: Our findings suggest that umbilical cord-derived MSCs’ conditioned media demonstrated the highest cytokine and growth factor levels and despite mostly pro-inflammatory cytokine profile were able to promote anti-inflammatory macrophage polarization. Conclusions: Umbilical cord-derived MSCs’ conditioned media hold great potential for therapeutic use, demonstrating significant anti-inflammatory effect on human macrophages.
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Mesenchymal stem cells, by secretion of IDO, IL-6, and PGE2, participate in the differentiation of macrophages to the immunosuppressive M2 phenotype.
“MSCs by secretion of IDO, IL-6, and PGE2 participate in the differentiation of macrophages to immunosuppressive M2 (tissue repair-associated) phenotype [80–82].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [81]
The Background and Discussion report that MSCs promote anti-inflammatory M2 macrophage polarization, including through PGE2, and discuss IL-6’s role in M2 polarization. Our copy does not establish IDO secretion as part of that mechanism (searched: IDO and indoleamine 2,3-dioxygenase), so the three-factor claim is only partly supported. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Peshkova, M., Korneev, A., Suleimanov, S., Vlasova, I. I., Svistunov, A., Kosheleva, N., & Timashev, P.
- Affiliations
- Sechenov University (RU)
- Corresponding author
- Timashev, Peter
- ORCID
- Venue
- Stem Cell Research & Therapy
- Published
- 2023-05-25
- Volume
- 14
- Issue
- 1
- Pages
- 142-142
- ISSN
- 1757-6512 (ISSN-L)
- PMC
- PMC10214600
- OpenAlex
- W4378213390
- Cited by
- 75
- References
- 58
- Citations by year
- 2026: 23 · 2025: 25 · 2024: 23 · 2023: 4
- FWCI
- 13.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Stem Cell Research & Therapy (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Science and Higher Education of the Russian Federation (No. 075-15-2021-951 (13.2251.21.0022))
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- mesenchymal stem cells, conditioned medium, secretome, cytokines, growth factors, macrophage polarization, paracrine effects, immunomodulation, 3D cell culture, cell spheroids, umbilical cord-derived MSCs, adipose-derived MSCs, bone marrow-derived MSCs, anti-inflammatory macrophages, inflammatory cytokines
- MeSH terms
- Female, Humans, Leukocytes, Mononuclear, Macrophages, Pregnancy, Cytokines, Culture Media, Conditioned, Intercellular Signaling Peptides and Proteins
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