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21-03-2024 | Dexamethasone | Original Article

Synergistic effects of mesenchymal stem cell-derived extracellular vesicles and dexamethasone on macrophage polarization under inflammatory conditions

Authors: Zahra Mirsanei, Fatemeh Jamshidi-Adegani, Saeid Vakilian, Fateme Ahangari, Sara Soufihasanabad, Khamis Al-Riyami, Sara Soudi, Sahar Ghaffari Khaligh, Sulaiman Al-Hashmi, Seyed Mahmoud Hashemi

Published in: Inflammopharmacology | Issue 2/2024

Abstract

The undesirable inflammation and the excessive M1 macrophage activity may lead to inflammatory diseases. Corticosteroids and stem cell therapy are used in clinical practice to promote anti-inflammatory responses. However, this protocol has limitations and is associated with numerous side effects. In this study, the synergistic anti-inflammatory effects of dexamethasone (Dex) and mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) were evaluated to enhance the polarization of M1 inflammatory macrophages into the anti-inflammatory (M2) phenotype. Hence, we designed different combinations of Dex and EVs using three methods, including EVs isolated from Dex-preconditioned MSCs (Pre-Dex-EVs), EVs loaded with Dex (L-Dex-EVs), and EVs and Dex co-administration (Dex + EVs). All designed EVs had a significant effect on reducing the expression of M1-related genes (iNOS, Stat1, and IRF5), cytokines (IL6 and TNF-a), and CD markers (CD86) in lipopolysaccharide-stimulated macrophages. On the other hand, these combinations promoted the expression of alternative-activated M2-related genes (Arg-1, Stat6, and IRF4), cytokine (IL10), and CD markers (CD206).

The combination of Dex and MSC-EVs enhances the effectiveness of both and synergistically promotes the conversion of inflammatory macrophages into an anti-inflammatory state.

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Title: Synergistic effects of mesenchymal stem cell-derived extracellular vesicles and dexamethasone on macrophage polarization under inflammatory conditions
Authors: Zahra Mirsanei
Fatemeh Jamshidi-Adegani
Saeid Vakilian
Fateme Ahangari
Sara Soufihasanabad
Khamis Al-Riyami
Sara Soudi
Sahar Ghaffari Khaligh
Sulaiman Al-Hashmi
Seyed Mahmoud Hashemi
Publication date: 21-03-2024
Publisher: Springer International Publishing
Keyword: Dexamethasone
Published in: Inflammopharmacology / Issue 2/2024
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-024-01438-7

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Synergistic effects of mesenchymal stem cell-derived extracellular vesicles and dexamethasone on macrophage polarization under inflammatory conditions

Abstract

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Abstract

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