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

• Published in: Inflammopharmacology Vol. 32; no. 2; pp. 1317 - 1332
• Main Authors: Mirsanei, Zahra, Jamshidi-Adegani, Fatemeh, Vakilian, Saeid, Ahangari, Fateme, Soufihasanabad, Sara, Al-Riyami, Khamis, Soudi, Sara, Ghaffari Khaligh, Sahar, Al-Hashmi, Sulaiman, Hashemi, Seyed Mahmoud
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2024
• Subjects: Allergology; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cytokines - metabolism; Dermatology; Dexamethasone - pharmacology; Extracellular Vesicles - metabolism; Gastroenterology; Immunology; Macrophages; Mesenchymal Stem Cells - metabolism; Original Article; Pharmacology/Toxicology; Rheumatology; Macrophage Polarization; Synergistic Effects; Inflammation; Dexamethasone; Mesenchymal Stem Cell; Extracellular Vesicle
• ISSN: 0925-4692; 1568-5608
• DOI: 10.1007/s10787-024-01438-7

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.