Background/Aims: Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. Methods: Human iPSCs were differentiated into iMSCs using a modified onestep method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. Results: Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. Conclusions: The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.

We investigated the phenotype and molecular signatures of CD8 + T cell subsets in kidneytransplant recipients (KTRs) with biopsy-proven T cell-mediated rejection (TCMR). We included 121 KTRs and divided them into three groups according to the pathologic or clinical diagnosis: Normal biopsy control (NC)(n = 32), TCMR (n = 50), and long-term graft survival (LTGS)(n = 39). We used flowcytometry and microarray to analyze the phenotype and molecular signatures of CD8 + T cell subsets using peripheral blood from those patients and analyzed significant gene expressions according to CD8 + T cell subsets. We investigated whether the analysis of CD8 + T cell subsets is useful for predicting the development of TCMR. CCR7 + CD8 + T cells significantly decreased, but CD28 null CD57 + CD8 + T cells and CCR7-CD45RA + CD8 + T cells showed an increase in the TCMR group compared to other groups (p<0.05 for each); hence CCR7 + CD8 + T cells showed significant negative correlations to both effector CD8 + T cells. We identified genes significantly associated with the change of CCR7 + CD8 + T, CCR7-CD45RA + CD8 + T, and CD28 null CD57 + CD8 + T cells in an ex vivo study and found that most of them were included in the significant genes on in vitro CCR7 + CD8 + T cells. Finally, the decrease of CCR7 + CD8 + T cells relative to CD28 null CD57 + T or CCR7-CD45RA + CD8 + T cells can predict TCMR significantly in the whole clinical cohort. In conclusion, phenotype and molecular signature of CD8 + T subsets showed a significant relationship to the development of TCMR; hence monitoring of CD8 + T cell subsets may be a useful for predicting TCMR in KTRs.

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