Pyroptosis-preconditioned mesenchymal stromal cell-derived extracellular vesicles as advanced nanomedicines for treating inflammatory diseases

, pyroptosis-preconditioned MSC-EVs (P-EVs) treatment has greater potential to suppress cytokine expression and cell death in pyroptotic macrophages than treatment with normal MSC-EVs (N-EVs). Compared with N-EV treatment, P-EV treatment showed superior potency in attenuating proinflammatory cell infiltration, cytokine/chemokine expression, resident tissue cell death, and the severity of pathological injury in different models of inflammatory diseases (acute lung or kidney injury), and these effects are likely the joint result of diverse functional cargos delivered by such EVs. This study highlights that pyroptosis preconditioning is a promising strategy for the highly efficient production of MSC-EVs with advanced therapeutic potential for treating diverse inflammatory diseases.