Mesenchymal stem cell derived exosomes mitigate COVID-19 cytokine storm via Annexin A1 and TGF-β mediated MAPK pathway inhibition

• MSC-Exos downregulate MAPK pathway genes (MEKK1, MEKK2, MEKK3) and reduce phosphorylation of JNK1, p38, and ERK1/2 in SARS-CoV-2-infected hamsters. • MSC-Exos treatment significantly lowers pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, mitigating the cytokine storm. • Histological analysis shows improved lung tissue structure with reduced alveolar wall thickness and immune cell infiltration after MSC-Exos therapy. • Molecular docking suggests direct interactions between exosomal proteins (Annexin A1, TGF-β) and MAPK components, providing a mechanistic basis for immunomodulation.