The secretome of periodontal ligament stem cells from MS patients protects against EAE
Open accessAbstract
Manipulation of stem cells or stem cells-derived secretome has emerged as a novel alternative therapeutic option for multiple sclerosis (MS). Here we show that human periodontal ligament stem cells (hPDLSCs)-derived conditioned medium (hPDLSCs-CM) and purified exosomes/microvesicles (hPDLSCs-EMVs) obtained from Relapsing Remitting (RR)-MS patients and healthy donors block experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing anti-inflammatory and immunosuppressive effects in spinal cord and spleen, and reverse disease progression by restoring tissue integrity via remyelination in the spinal cord. We show that hPDLSCs-CM and hPDLSCs-EMVs reduce pro-inflammatory cytokines IL-17, IFN-γ, IL-1β, IL-6, TNF-α, and induce anti-inflammatory IL-10. In addition, apoptosis related STAT1, p53, Caspase 3, and Bax expressions were attenuated. Our findings unravel the immunosuppressive effects of hPDLSCs-CM and hPDLSCs-EMVs in EAE mice, and suggest simple alternative autologous source for patient-customized cell-free targeting treatment in MS patients.
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IL-10 released by MSCs limits the pro-inflammatory state of polymorphonuclear neutrophils.
“IL-10 released by MSCs appeared to limit the pro-inflammatory state of polymorphonuclear neutrophils [69].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [69]
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Foust, K. D., Wang, X., McGovern, V. L., Braun, L., Bevan, A. K., Haidet, A. M., Le, T. T., Morales, P. R., Rich, M. M., Burghes, A. H. M., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1610 · Cited by 688 · see citing works
RetractedSex differences in experimental autoimmune encephalomyelitis in multiple murine strains
Papenfuss, T. L., Rogers, C. J., Gienapp, I., Yurrita, M., McClain, M., Damico, N., Valo, J., Song, F., & Whitacre, C. C. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.01.018 · Cited by 152 · see citing works
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Cited by
Sorted by citations
Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine
Vizoso, F., Eiro, N., Cid, S., Schneider, J., & Perez-Fernandez, R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091852 · Cited by 1,363 · see citing works
Mesenchymal stem cell secretome for regenerative medicine: Where do we stand?
Trigo, C. M., Rodrigues, J. S., Camões, S. P., Solá, S., & Miranda, J. P. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2024.05.004 · Cited by 205 · see citing works
“Further, in a model of endotoxin-induced lung injury, the MSC-derived-EVs inhibited the migration of neutrophils into the lung [42,68] while IL-10 released by MSCs appeared to limit the pro-inflammatory state of polymorphonuclear neutrophils [69].”
- Authors
- Rajan, T. S., Giacoppo, S., Diomede, F., Ballerini, P., Paolantonio, M., Marchisio, M., Piattelli, A., Bramanti, P., Mazzon, E., & Trubiani, O.
- Affiliations
- Centro Neurolesi Bonino Pulejo (IT)
- University of Chieti-Pescara (IT)
- Corresponding author
- Mazzon, Emanuela
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-12-07
- Volume
- 6
- Issue
- 1
- Pages
- 38743-38743
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5141419
- OpenAlex
- W2560630866
- Cited by
- 109
- References
- 2
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 9 · 2023: 12 · 2022: 14 · 2021: 13 · 2020: 13 · 2019: 15 · 2018: 13 · 2017: 9
- FWCI
- 11.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- multiple sclerosis, periodontal ligament stem cells, secretome, exosomes, microvesicles, conditioned medium, experimental autoimmune encephalomyelitis, immunosuppression, remyelination, inflammatory cytokines, anti-inflammatory cytokines, apoptosis, cell-free therapy, autologous stem cell therapy
- MeSH terms
- Animals, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Male, Multiple Sclerosis, Periodontal Ligament, Stem Cells, Cytokines, Apoptosis Regulatory Proteins, Mice, Cell-Derived Microparticles, Exosomes
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