Abstract
BackgroundEmbryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear.MethodsIn this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro.ResultsWe found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9+ cells.ConclusionsESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.
Highlights
Acute kidney injury (AKI) is a syndrome characterized by rapid loss of renal excretory function that happens within a few hours or a few days, which is often associated with a variety of short- and long-term complications [1, 2].Without prompt treatment, AKI can progress to chronic kidney disease (CKD), end-stage renal disease (ESRD), or even to death as it can lead to the formation of fluid and waste in the body, which is life-threatening [3, 4]
Characterization of extracellular vesicles derived from Embryonic stem cell (ESC) and mouse embryonic fibroblasts (MEF) Using ultracentrifugation, ESC-Extracellular vesicles (EVs) and MEF-EVs were isolated from the supernatant of ESCs and MEF cells, respectively
The transmission electron microscope (TEM) image showed that Embryonic stem cell-derived extracellular vesicles (ESC-EVs) and MEF-EVs were all round vesicles wrapped in membranes
Summary
Acute kidney injury (AKI) is a syndrome characterized by rapid loss of renal excretory function that happens within a few hours or a few days, which is often associated with a variety of short- and long-term complications [1, 2]. AKI can progress to chronic kidney disease (CKD), end-stage renal disease (ESRD), or even to death as it can lead to the formation of fluid and waste in the body, which is life-threatening [3, 4]. AKI threatens the health and life of patients for its higher. Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. The roles and mechanisms of ESC-EVs on AKI remain unclear
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