Adipose-derived mesenchymal stem cells secreted EVs: a potential cell-free therapy for canine renal ischemia-reperfusion injury

Abstract: Canine renal ischemia-reperfusion (IR) causes severe acute kidney injury characterized by renal dysfunction and inflammatory disorder. Adipose-derived mesenchymal stem cells (ADMSCs) and their extracellular vesicles (EVs) are pluripotent adult stem cells with promising therapy for IR, based on their potent anti-inflammatory and immunomodulatory properties. The aims of this study were to explore the therapeutic efficacy of ADMSC-EVs in canine renal IR injury. MSCs were isolated from inguinal fat tissue in dogs and their EVs were isolated from third-passage of ADMSC. ADMSCs were charactered by differentiation ability and surface makers. ADMSC-EVs were charactered by transmission electron microscopy, NTA and surface markers. Canine IR model was used with ADMSC-EVs administration to evaluated the therapeutic effect of inflammation, oxidate stress, mitochondrial damage and apoptosis. Renal IR injury leads to severe histopathological lesions and significantly increasing in biomarkers of renal function, inflammation, apoptosis; however, ADMSC more potently attenuated these lesions and inhibited apoptosis by reducing mitochondrial damage. The findings may provide a cell-free therapy for canine renal IR injury and reveal the mechanism involved.