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Fig. 6 | Stem Cell Research & Therapy

Fig. 6

From: Spotlight on therapeutic efficiency of mesenchymal stem cells in viral infections with a focus on COVID-19

Fig. 6

COVID-19 leads to cell and damage injury, discharge of danger-associated molecular patterns (DAMPs), PAMPs, and inflammatory intermediates that increase immune cell penetration. Injected MSCs-EVs can decrease inflammation and induce tissue regeneration. Significantly, the good efficacy of MSCs is displayed to be related to the decrease in TNF-α, interleukin-1/6 via the discharge of HGF, PGE2, lipoxin A4 (LXA4), and TSG-6, inhibition of inflammatory T cell proliferation via indoleamine 2,3-dioxygenase expression, switch from Th1 and Th17 reactions to Th2, and suppression of monocytes and myeloid DCs maturation. MSCs stimulate M2 polarization via juxtacrine signaling and paracrine agents, including HGF, PGE2, and TSG-6, leading to a monocyte helping enhance anti-inflammatory IL-10, which synergistically induces Treg cells and activates tissue regeneration pathways. Additionally, MSC involvement in several mechanisms that increase lung fibrosis leads to protecting efficacy, as shown in various lung damage models. Notably, MSCs decrease the damage-associated alveolar edema and endothelial permeance via the discharge of keratinocyte KGF to increase the sodium-affiliate alveolar fluid clearance via epithelial sodium channel (ENaC) and have anti-apoptotic and anti-oxidative pathways to repair cytokine-injured alveolar type II cells and epithelial and endothelial damage via the discharge of angiopoietin-1, lipoxin A4 (LXA4) and TSG-6 [135]

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