The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells

IntroductionExosomes (EXOs) as a targeted cell-free therapy could offer a new therapeutic strategy for immune-mediated inflammatory diseases, due to their stability and ease of storage and handling. This study focused on exosomes derived from stem cells of human exfoliated deciduous teeth (SHED-MSC-...

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Main Authors: Ali Fallah, Abasalt Hosseinzadeh Colagar, Ayyoob Khosravi, Azadeh Mohammad-Hasani, Mohsen Saeidi
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1550280/full
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author Ali Fallah
Abasalt Hosseinzadeh Colagar
Ayyoob Khosravi
Ayyoob Khosravi
Azadeh Mohammad-Hasani
Azadeh Mohammad-Hasani
Mohsen Saeidi
Mohsen Saeidi
author_facet Ali Fallah
Abasalt Hosseinzadeh Colagar
Ayyoob Khosravi
Ayyoob Khosravi
Azadeh Mohammad-Hasani
Azadeh Mohammad-Hasani
Mohsen Saeidi
Mohsen Saeidi
author_sort Ali Fallah
collection DOAJ
description IntroductionExosomes (EXOs) as a targeted cell-free therapy could offer a new therapeutic strategy for immune-mediated inflammatory diseases, due to their stability and ease of storage and handling. This study focused on exosomes derived from stem cells of human exfoliated deciduous teeth (SHED-MSC-EXOs) and their role in managing the balance of immunoregulatory macromolecules that play a role in the underlying immunoregulatory mechanisms in THP-1-derived M0/M1 macrophage cells.MethodsFlow cytometry confirmed the expression of CD14, CD68, CD80, and CD86 markers in these macrophages. Following morphological and survival assessments, culture supernatants from SHED-MSCs were used to isolate exosomes. Once the exosomes were verified, Calcein AM-labeled EXOs were introduced to the macrophage cells. The immunoregulatory macromolecules were assessed by analyzing surface markers, cytokine production, and pro- and antioxidant activity.ResultsMacrophages treated with exosomes exhibited immunomodulatory effects akin to those treated with dexamethasone. The levels of anti-inflammatory and antioxidant markers, including CD206, Arg-1, IL-10, TGF-β, TAC, CAT, and SOD, which act as immunosuppressive macromolecules, were elevated. In contrast, there was a reduction in pro-inflammatory and pro-oxidant markers, including CD80, CD81, IL-6R, IL-12, TNF-α, MDA, and NO, which act as immunostimulatory macromolecules (P < 0.05).DiscussionThe findings suggest that exosomes derived from SHED-MSC can skew M0/M1 macrophages to the M2 phenotype and inhibit M1 polarization. These nanovesicles, with their distinct physical properties and ability to penetrate target cells, may prove beneficial in conditions involving the depletion of M2 macrophages and M1 macrophage-induced diseases, potentially aiding in the reduction of inflammation and tissue injury.
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spelling doaj-art-a836a5eb8fd64e1aaa1f4c0a678d85ef2025-02-07T06:49:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15502801550280The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cellsAli Fallah0Abasalt Hosseinzadeh Colagar1Ayyoob Khosravi2Ayyoob Khosravi3Azadeh Mohammad-Hasani4Azadeh Mohammad-Hasani5Mohsen Saeidi6Mohsen Saeidi7Department of Molecular and Cell Biology, Faculty of Basic Science, University of Mazandaran, Babolsar, IranDepartment of Molecular and Cell Biology, Faculty of Basic Science, University of Mazandaran, Babolsar, IranStem Cell Research Centre, Golestan University of Medical Sciences, Gorgan, IranDepartment of Molecular Medicine, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, IranDepartment of Molecular and Cell Biology, Faculty of Basic Science, University of Mazandaran, Babolsar, IranDepartment of Molecular Medicine, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, IranStem Cell Research Centre, Golestan University of Medical Sciences, Gorgan, IranDepartment of Immunology, School of Medicine, Golestan University of Medical Sciences, Gorgan, IranIntroductionExosomes (EXOs) as a targeted cell-free therapy could offer a new therapeutic strategy for immune-mediated inflammatory diseases, due to their stability and ease of storage and handling. This study focused on exosomes derived from stem cells of human exfoliated deciduous teeth (SHED-MSC-EXOs) and their role in managing the balance of immunoregulatory macromolecules that play a role in the underlying immunoregulatory mechanisms in THP-1-derived M0/M1 macrophage cells.MethodsFlow cytometry confirmed the expression of CD14, CD68, CD80, and CD86 markers in these macrophages. Following morphological and survival assessments, culture supernatants from SHED-MSCs were used to isolate exosomes. Once the exosomes were verified, Calcein AM-labeled EXOs were introduced to the macrophage cells. The immunoregulatory macromolecules were assessed by analyzing surface markers, cytokine production, and pro- and antioxidant activity.ResultsMacrophages treated with exosomes exhibited immunomodulatory effects akin to those treated with dexamethasone. The levels of anti-inflammatory and antioxidant markers, including CD206, Arg-1, IL-10, TGF-β, TAC, CAT, and SOD, which act as immunosuppressive macromolecules, were elevated. In contrast, there was a reduction in pro-inflammatory and pro-oxidant markers, including CD80, CD81, IL-6R, IL-12, TNF-α, MDA, and NO, which act as immunostimulatory macromolecules (P < 0.05).DiscussionThe findings suggest that exosomes derived from SHED-MSC can skew M0/M1 macrophages to the M2 phenotype and inhibit M1 polarization. These nanovesicles, with their distinct physical properties and ability to penetrate target cells, may prove beneficial in conditions involving the depletion of M2 macrophages and M1 macrophage-induced diseases, potentially aiding in the reduction of inflammation and tissue injury.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1550280/fullSHED-MSCsexosomeimmunoregulatory macromoleculesmacrophage polarizationimmunomodulation
spellingShingle Ali Fallah
Abasalt Hosseinzadeh Colagar
Ayyoob Khosravi
Ayyoob Khosravi
Azadeh Mohammad-Hasani
Azadeh Mohammad-Hasani
Mohsen Saeidi
Mohsen Saeidi
The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells
Frontiers in Immunology
SHED-MSCs
exosome
immunoregulatory macromolecules
macrophage polarization
immunomodulation
title The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells
title_full The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells
title_fullStr The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells
title_full_unstemmed The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells
title_short The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells
title_sort role of natural exosomes from shed msc in immunoregulation of m0 m1 polarized macrophage cells
topic SHED-MSCs
exosome
immunoregulatory macromolecules
macrophage polarization
immunomodulation
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1550280/full
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