• Priming induced mesenchymal stem cells (iMSCs) with the pan-PPAR agonist lanifibranor enhances the therapeutic efficacy of their extracellular vesicles (EVs) against acute kidney injury (AKI).
• Pan-PPAR-iMSC-EVs significantly reduce inflammation, immune cell infiltration, and apoptosis in a cisplatin-induced AKI mouse model, while increasing renal capillary density.
• In vitro, pan-PPAR-iMSC-EVs promote HK-2 cell proliferation and survival under cisplatin-induced apoptosis and suppress inflammatory cytokine expression in M1-polarized THP-1 cells more effectively than unprimed iMSC-EVs.
• This study presents a novel cell-free therapeutic strategy for AKI, potentially overcoming limitations of direct MSC use and offering a more potent EV-based treatment.