Extracellular vesicles from induced pluripotent stem cell-derived mesenchymal stem cells enhance the recovery of acute kidney injury

Background aims To investigate whether the extracellular vesicles (EVs) from mesenchymal stem cell–like cells derived from induced pluripotent stem cells (iMSC-EVs) can inhibit the progression of acute kidney injury (AKI). Methods The characteristics of iMSC-EVs were confirmed by immunoblotting, cryo-transmission electron microscopy, nanoparticle tracking analysis, and their localization in kidneys. Using human renal epithelial cells, the potential of iMSC-EVs to stimulate the growth and survival of HK-2 cells undergoing cisplatin-induced cell death was investigated. The anti-inflammatory effects of iMSC-EVs was examined in M1-polarized THP-1 macrophages. Subsequently, the therapeutic potential of iMSC-EVs was assessed in cisplatin-induced acute kidney injury in BALB/c mice. The anti-apoptotic and anti-inflammatory effect of iMSC-EVs was evaluated using serum biochemistry, histology, immunohistochemistry, and gene expression analysis. Results iMSC-EVs promoted the growth of renal epithelial cell (HK-2) and enhanced the survival of HK-2 undergoing cisplatin-induced cell death. In cisplatin-induced mice with AKI, iMSC-EVs alleviated AKI, as shown by reduced blood nitrogen urea/creatinine and increased body weight. Also, iMSC-EVs enhanced renal tissue integrity and the number of proliferating cell nuclear antigen–positive tubules. iMSC-EVs decreased the infiltration of immune cells, reduced the expression of inflammatory genes in M1-induced THP-1 cells and enhanced capillary density in the kidney of AKI mice. Real-time quantitative polymerase chain reaction analysis showed that the expression of inflammatory genes in the kidney of AKI mice was reduced compared with that received vehicle. Immunoblotting revealed that iMSC-EVs led to a decreased protein expression of key inflammatory genes. Also, iMSC-EVs reversed the activation of ERK1/2 signaling induced by AKI. Finally, iMSC-EVs inhibited the apoptosis of HK-2 cells induced by cisplatin as well as that of renal tissue of AKI mice. Conclusions Our data suggest that iMSC-EVs have potential to become a novel, cell-free therapeutic for cisplatin-induced AKI.