The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Human Mesenchymal Stem Cells Inhibit Neutrophil Apoptosis: A Model for Neutrophil Preservation in the Bone Marrow Niche
Abstract
Mesenchymal stem cells (MSC) establish close interactions with bone marrow sinusoids in a putative perivascular niche. These vessels contain a large storage pool of mature nonproliferating neutrophils. Here, we have investigated the effects of human bone marrow MSC on neutrophil survival and effector functions. MSC from healthy donors, at very low MSC:neutrophil ratios (up to 1:500), significantly inhibited apoptosis of resting and interleukin (IL)-8-activated neutrophils and dampened N-formyl-l-methionin-l-leucyl-l-phenylalanine (f-MLP)-induced respiratory burst. The antiapoptotic activity of MSC did not require cell-to-cell contact, as shown by transwell experiments. Antibody neutralization experiments demonstrated that the key MSC-derived soluble factor responsible for neutrophil protection from apoptosis was IL-6, which signaled by activating STAT-3 transcription factor. Furthermore, IL-6 expression was detected in MSC by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Finally, recombinant IL-6 was found to protect neutrophils from apoptosis in a dose-dependent manner. MSC had no effect on neutrophil phagocytosis, expression of adhesion molecules, and chemotaxis in response to IL-8, f-MLP, or C5a. These results support the following conclusions: (a) in the bone marrow niche, MSC likely protect neutrophils of the storage pool from apoptosis, preserving their effector functions and preventing the excessive or inappropriate activation of the oxidative metabolism, and (b) a novel mechanism whereby the inflammatory potential of activated neutrophils is harnessed by inhibition of apoptosis and reactive oxygen species production without impairing phagocytosis and chemotaxis has been identified. Disclosure of potential conflicts of interest is found at the end of this article.
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Cited by
Multipotent mesenchymal stromal cells and the innate immune system
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Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential
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Stem Cell Paracrine Actions and Tissue Regeneration
Baraniak, P. R., & McDevitt, T. C. (2010) · Regenerative Medicine · doi:10.2217/rme.09.74 · Cited by 843
Mesenchymal Stem Cells as Therapeutics
Parekkadan, B., & Milwid, J. M. (2010) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-070909-105309 · Cited by 759
Immune modulation by mesenchymal stem cells
Jiang, W., & Xu, J. (2020) · Cell Proliferation · doi:10.1111/cpr.12712 · Cited by 650
Metadata
- Authors
- Raffaghello, L., Bianchi, G., Bertolotto, M., Montecucco, F., Busca, A., Dallegri, F., Ottonello, L., & Pistoia, V.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-10-11
- Volume
- 26
- Issue
- 1
- Pages
- 151-162
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2039251191
- Cited by
- 517
- References
- 61
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Human Mesenchymal Stem Cells Inhibit Neutrophil Apoptosis: A Model for Neutrophil Preservation in the Bone Marrow Niche. https://app.cochat.ai/papers/10.1634/stemcells.2007-0416
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- Raffaghello, L., Bianchi, G., Bertolotto, M., Montecucco, F., Busca, A., Dallegri, F., Ottonello, L., & Pistoia, V. (2008). Human Mesenchymal Stem Cells Inhibit Neutrophil Apoptosis: A Model for Neutrophil Preservation in the Bone Marrow Niche. Stem Cells. https://doi.org/10.1634/stemcells.2007-0416
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