Therapeutic Potential of Pretreatment with Exosomes Derived from Stem Cells from the Apical Papilla against Cisplatin-Induced Acute Kidney Injury.

Abstract

Acute kidney injury (AKI) is the most serious side effect of treatment with cisplatin in clinical practice. The aim of this study was to investigate the therapeutic effect of exosomes derived from stem cells from the apical papilla (SCAPs) on AKI. The medium from a SCAP culture was collected after 2 d of culture. From this, SCAP-derived exosomes (SCAP-ex), which were round (diameter: 30–150 nm) and expressed the characteristic proteins CD63 and CD81, were collected via differential ultracentrifugation. Rat renal epithelial cells (NRK-52E) were pretreated with SCAP-ex for 30 min and subsequently treated with cisplatin to induce acute injury. The extent of oxidative stress, inflammation, and apoptosis were used to evaluate the therapeutic effect of SCAP-ex against cisplatin-induced nephrotoxicity. The viability assay showed that the survival of damaged cells increased from 65% to 89%. The levels of reactive oxygen species decreased from 176% to 123%. The glutathione content increased by 78%, whereas the levels of malondialdehyde and tumor necrosis factor alpha (TNF-α) decreased by 35% and 9%, respectively. These results showed that SCAP-ex can retard oxidative stimulation in damaged kidney cells. Quantitative reverse transcription–polymerase chain-reaction gene analysis showed that they can also reduce the expression of nuclear factor-κβ (NF-κβ), interleukin-1β (IL-1β), and p53 in AKI. Further, they increased the gene expression of antiapoptotic factor B-cell lymphoma-2 (Bcl-2), whereas they reduced that of proapoptotic factors Bcl-2-associated X (Bax) and caspase-8 (CASP8), CASP9, and CASP3, thereby reducing the risk of cell apoptosis.