Protective Effect of Msc-Derived Exosomes Against Cisplatin-Induced Apoptosis Via Heat Shock Protein 70 in Auditory Explant Model

Background: Therapeutics based on stem cell technology, including stem cell-derived exosomes, have emerged in recent years for the treatment of what were otherwise considered incurable diseases. Cisplatin, used as an anticancer drug, is toxic to auditory hair cells in an ex vivo cochlear explant model. In this study, we evaluated the efficacy of human mesenchymal stem cell (MSC)-derived exosomes for protection against ototoxic hearing loss. Method: The cochlea explant extracted from the mouse set up to analyze ex-vivo condition. Bone marrow MSC was co-cultured with cochlear explants and then cisplatin was added to the pretreatment technique. After co-culture, the medium and cells in each well were sorted to compare the amount of protein expressed by the exosome and apoptosis markers. Findings: Incubation with MSC-derived exosomes prior to cisplatin addition induced a decrease in cisplatin-induced drug toxicity in auditory hair cells, but not when exosomes were introduced concurrently with or after cisplatin. The delivery of MSC-derived exosomes to cochlear explants was confirmed by the increasing protein levels of the exosome markers CD63 and HSP70. MSC-derived exosomes inhibited drug-induced apoptosis in the cochlear explant model. Interpretation: These results were consistent with those from a model in which MSC-derived exosomes protect auditory hair cells from cisplatin-induced drug toxicity in an ex vivo cochlear explant model and support future studies into the therapeutic benefits of stem cell-derived exosomes in clinical applications. Funding Statement: Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (grant number: HI19C1334). Ethics statement: The animal protocols used in this work were evaluated and approved by the institutional animal care and use committee in the animal laboratory of Yonsei University in Wonju College of Medicine (Protocol YWC-180703-1). Declaration of interests: There are no conflicts to declare.