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

Autor: Sadeghi M; Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.; Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.; Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Dehnavi S; Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Khodadadi A; Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Ghadiri AA; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Ganji A; Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran., Sharifat M; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Asadirad A; Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ali.asadirad@gmail.com.; Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ali.asadirad@gmail.com.; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ali.asadirad@gmail.com.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2024 Dec 18; Vol. 15 (1), pp. 481. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1186/s13287-024-04099-z
Abstrakt: 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.
Competing Interests: Declarations. Ethics approval and consent to participate: This study is based on the approved project entitled “Evaluation the efficacy of sublingually administrated OVA-encapsulated Adipose-derived mesenchymal stem cell-derived exosome nanoparticles modified by DC-specific aptamer in allergic mouse model”. All experiments were approved by the Institutional Animal Ethics Committee of the Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (Approval number: IR.AJUMS.ABHC.REC.1399.059) (Date of approval: 2021.1.12). In addition, this work has been reported in line with the ARRIVE guidelines 2.0. Conflict of interest: All authors declare no potential conflict of interest. AI declaration: The authors declare that they have not use AI-generated work in this manuscript.
(© 2024. The Author(s).)
Databáze: MEDLINE
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