Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model

Abstract Introduction Sublingual immunotherapy (SLIT) is an effective and injection-free route for allergen-specific immunotherapy (AIT). Mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo) has been identified as a novel delivery platform with immunomodulatory capacities. In addition, targeti...

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Main Authors: Mahvash Sadeghi, Sajad Dehnavi, Ali Khodadadi, Ata. A. Ghadiri, Ali Ganji, Moosa Sharifat, Ali Asadirad
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-024-04099-z
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author Mahvash Sadeghi
Sajad Dehnavi
Ali Khodadadi
Ata. A. Ghadiri
Ali Ganji
Moosa Sharifat
Ali Asadirad
author_facet Mahvash Sadeghi
Sajad Dehnavi
Ali Khodadadi
Ata. A. Ghadiri
Ali Ganji
Moosa Sharifat
Ali Asadirad
author_sort Mahvash Sadeghi
collection DOAJ
description Abstract Introduction Sublingual immunotherapy (SLIT) is an effective and injection-free route for allergen-specific immunotherapy (AIT). Mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo) has been identified as a novel delivery platform with immunomodulatory capacities. In addition, targeting agents such as aptamers (Apt) have been extensively used for specific delivery approaches such as direct delivery of allergen formulations to dendritic cells (DC) to improve the efficacy of specific immunotherapy. In this study, we assessed the effects of MSC-derived Exos containing ovalbumin (Ova) which decorated with DC-specific aptamer in allergic rhinitis mice model. Materials and methods Exos were harvested from adipose tissue-derived MSCs, and Exo-Apt-Ova complex was formulated. Then, Ova-induced allergic asthma model was simulated and sensitized BALB/c mice were treated sublingually with Exo-Apt-Ova complex (5 µg Ova) twice weekly for 8 weeks. Ova-specific IgE levels in serum and concentrations of interferon-gamma (IFN-γ), interleukin (IL)-4, and transforming growth factor-beta (TGF-β) in the supernatant of cultured splenocytes were evaluated using enzyme-linked immunosorbent assay (ELISA). In addition, lung histologic analysis and nasopharyngeal lavage fluid (NALF) cell count were performed. Results Administration of Ova-incorporated Apt-modified Exos dramatically increased IFN-γ and TGF-β levels, and decreased IL-4 and IgE levels. In addition, inflammatory responses in the lung tissue and the number of eosinophils in NALF decreased. Conclusion SLIT using Exo-Ova (5 µg) decorated with DC-specific aptamer induced immunomodulatory responses and remarkably attenuated allergic airway inflammation in mice.
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spelling doaj-art-c2f914cc9e9f4f809e5c453878128b072024-12-22T12:18:44ZengBMCStem Cell Research & Therapy1757-65122024-12-0115111210.1186/s13287-024-04099-zImmunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse modelMahvash Sadeghi0Sajad Dehnavi1Ali Khodadadi2Ata. A. Ghadiri3Ali Ganji4Moosa Sharifat5Ali Asadirad6Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical SciencesAllergy Research Center, Mashhad University of Medical SciencesCancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical SciencesMolecular and Medicine Research Center, Arak University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical SciencesCellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical SciencesAbstract Introduction Sublingual immunotherapy (SLIT) is an effective and injection-free route for allergen-specific immunotherapy (AIT). Mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo) has been identified as a novel delivery platform with immunomodulatory capacities. In addition, targeting agents such as aptamers (Apt) have been extensively used for specific delivery approaches such as direct delivery of allergen formulations to dendritic cells (DC) to improve the efficacy of specific immunotherapy. In this study, we assessed the effects of MSC-derived Exos containing ovalbumin (Ova) which decorated with DC-specific aptamer in allergic rhinitis mice model. Materials and methods Exos were harvested from adipose tissue-derived MSCs, and Exo-Apt-Ova complex was formulated. Then, Ova-induced allergic asthma model was simulated and sensitized BALB/c mice were treated sublingually with Exo-Apt-Ova complex (5 µg Ova) twice weekly for 8 weeks. Ova-specific IgE levels in serum and concentrations of interferon-gamma (IFN-γ), interleukin (IL)-4, and transforming growth factor-beta (TGF-β) in the supernatant of cultured splenocytes were evaluated using enzyme-linked immunosorbent assay (ELISA). In addition, lung histologic analysis and nasopharyngeal lavage fluid (NALF) cell count were performed. Results Administration of Ova-incorporated Apt-modified Exos dramatically increased IFN-γ and TGF-β levels, and decreased IL-4 and IgE levels. In addition, inflammatory responses in the lung tissue and the number of eosinophils in NALF decreased. Conclusion SLIT using Exo-Ova (5 µg) decorated with DC-specific aptamer induced immunomodulatory responses and remarkably attenuated allergic airway inflammation in mice.https://doi.org/10.1186/s13287-024-04099-zMesenchymal stromal/stem cell (MSC)Sublingual immunotherapy (SLIT)Extracellular vesicle (EV)Exosome (Exo)Targeted drug deliveryAptamer (Apt)
spellingShingle Mahvash Sadeghi
Sajad Dehnavi
Ali Khodadadi
Ata. A. Ghadiri
Ali Ganji
Moosa Sharifat
Ali Asadirad
Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model
Stem Cell Research & Therapy
Mesenchymal stromal/stem cell (MSC)
Sublingual immunotherapy (SLIT)
Extracellular vesicle (EV)
Exosome (Exo)
Targeted drug delivery
Aptamer (Apt)
title Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model
title_full Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model
title_fullStr Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model
title_full_unstemmed Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model
title_short Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model
title_sort immunomodulatory features of msc derived exosomes decorated with dc specific aptamer for improving sublingual immunotherapy in allergic mouse model
topic Mesenchymal stromal/stem cell (MSC)
Sublingual immunotherapy (SLIT)
Extracellular vesicle (EV)
Exosome (Exo)
Targeted drug delivery
Aptamer (Apt)
url https://doi.org/10.1186/s13287-024-04099-z
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