Interactions Between Human Mesenchymal Stem Cells and Natural Killer Cells
Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells representing an attractive therapeutic tool for regenerative medicine. They possess unique immunomodulatory properties, being capable of suppressing T-cell responses and modifying dendritic cell differentiation, maturation, and function, whereas they are not inherently immunogenic, failing to induce alloreactivity to T cells and freshly isolated natural killer (NK) cells. To clarify the generation of host immune responses to implanted MSCs in tissue engineering and their potential use as immunosuppressive elements, the effect of MSCs on NK cells was investigated. We demonstrate that at low NK-to-MSC ratios, MSCs alter the phenotype of NK cells and suppress proliferation, cytokine secretion, and cyto-toxicity against HLA-class I– expressing targets. Some of these effects require cell-to-cell contact, whereas others are mediated by soluble factors, including transforming growth factor–β1 and prostaglandin E2, suggesting the existence of diverse mechanisms for MSC-mediated NK-cell suppression. On the other hand, MSCs are susceptible to lysis by activated NK cells. Overall, these data improve our knowledge of interactions between MSCs and NK cells and consequently of their effect on innate immune responses and their contribution to the regulation of adaptive immunity, graft rejection, and cancer immunotherapy.
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The ratio between NK cells and MSCs is important for MSC-immunosuppressive-mediated effects.
“the ratio between NK and MSCs was found to be important for the MSC-immunosuppressive-mediated effects [86].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [86]
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“MSCs have been reported to inhibit the proliferation, activation, cytokine production, and cytotoxicity of IL-2 or IL-15-induced NK cells, mediated in part by IDO and PGE2 [155–157].”
- Authors
- Sotiropoulou, P. A., Perez, S. A., Gritzapis, A. D., Baxevanis, C. N., & Papamichail, M.
- Affiliations
- St Savas Hospital (GR)
- Corresponding author
- Sotiropoulou, Panagiota A.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-08-11
- Volume
- 24
- Issue
- 1
- Pages
- 74-85
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2024971445
- Cited by
- 956
- References
- 2
- Citations by year
- 2026: 6 · 2025: 19 · 2024: 24 · 2023: 34 · 2022: 45 · 2021: 55 · 2020: 49 · 2019: 51 · 2018: 55 · 2017: 58 · 2016: 72 · 2015: 55 · 2014: 56 · 2013: 83 · 2012: 63
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- mesenchymal stem cells, natural killer cells, immunomodulation, NK cell inhibition, NK cell-mediated lysis, TGF-β1, prostaglandin E2, cell-cell contact, graft rejection, cancer immunotherapy, innate immune response, cell-cell interactions
- MeSH terms
- Adult, Cell Communication, Dose-Response Relationship, Drug, Humans, Killer Cells, Natural, Phenotype, Histocompatibility Antigens Class I, Cytokines, Cell Death, Coculture Techniques, Interleukin-15, K562 Cells, Cell Line, Tumor, Cell Proliferation, Mesenchymal Stem Cells
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