The Immunomodulatory Functions of Mesenchymal Stromal/Stem Cells Mediated via Paracrine Activity
Open accessAbstract
Mesenchymal stromal/stem cells (MSCs) exist in almost all tissues, possessing the potential to differentiate into specialized cell types and exert immunomodulatory functions. Thus, they have attracted much attention as a promising therapeutic candidate. Recent studies have demonstrated that paracrine signaling is mainly responsible for the involvement of MSCs in the modulation of immune responses and the progression of diseases. Through release of secretome consisting of a diverse range of cytokines, chemokines, and extracellular vesicles (EVs), MSCs convey regulatory messages to recipient immune cells in the microenvironment. In this review, we focus on the recent advances in how MSCs contribute to immunomodulation through the secretion of paracrine factors. The further improved understanding of the molecular mechanism underlying the interactions between MSCs and immune cells highlights the paracrine biology of MSCs in the modulation of the immune microenvironment and promotes the clinical application of MSCs in regenerative medicine and immune diseases.
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BM-MSCs can reduce apoptosis of resting or activated neutrophils by releasing IL-6, TSG-6 and SOD3.
“by releasing IL-6 [42], TSG-6 [62] and superoxide dismutase (SOD3) [63], BM-MSCs can reduce apoptosis of neutrophils that are resting or activated [42]”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [63]
Section 3.1 (page unavailable) says MSC-produced IL-6 protects cocultured neutrophils from apoptosis. It links SOD3 to reduced neutrophil activation, not reduced apoptosis; Section 3.1 links TSG-6 to dendritic-cell maturation, not neutrophil apoptosis. The copy also does not specify that the apoptosis finding applies to both resting and activated neutrophils or specifically to BM-MSCs. (LLM, conf=0.87)
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Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential
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“In fact, the secretion of IL-10 is thought to affect the JAK1/STAT3 signaling pathway, as well as through the release of TNF-a , suppressing the MAPK and NF-j B signaling activation [63,76], signaling pathways which are involved in the production of pro-inflammatory modulators [77,78].”
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Single-Cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells
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Diagnostic and Therapeutic Potential of Extracellular Vesicles
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- Authors
- Zhou, Y., Yamamoto, Y., Xiao, Z., & Ochiya, T.
- Affiliations
- State Key Laboratory of Digital Medical Engineering (CN)
- National Cancer Center Research Institute (JP)
- Tokyo Medical University (JP)
- Corresponding author
- Ochiya, Takahiro
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2019-07-12
- Volume
- 8
- Issue
- 7
- Pages
- 1025
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC6678920
- OpenAlex
- W2958669483
- Cited by
- 303
- References
- 133
- Citations by year
- 2026: 24 · 2025: 34 · 2024: 41 · 2023: 39 · 2022: 60 · 2021: 59 · 2020: 39 · 2019: 7
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Project for Cancer Research and Therapeutic Evolution (17cm0106402h0002)
- MEXT KAKENHI (Grant-in-Aid for Young Scientists (A)) (17H04991)
- China Scholarship Council (201706090122)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- mesenchymal stem cells, immunomodulation, paracrine signaling, secretome, extracellular vesicles, cytokines, chemokines, immune microenvironment, regenerative medicine, immune disorders
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