Extracellular Vesicles in Acute Kidney Injury and Clinical Applications

Abstract

Acute kidney injury (AKI)––the sudden loss of kidney function due to tissue damage and subsequent progression to chronic kidney disease––has high morbidity and mortality rates and is a serious worldwide clinical problem. Current AKI diagnosis, which relies on measuring serum creatinine levels and urine output, cannot sensitively and promptly report on the state of damage. To address the shortcomings of these traditional diagnosis tools, several molecular biomarkers have been developed to facilitate the identification and ensuing monitoring of AKI. Nanosized membrane-bound extracellular vesicles (EVs) in body fluids have emerged as excellent sources for discovering such biomarkers. Besides this diagnostic purpose, EVs are also being extensively exploited to deliver therapeutic macromolecules to damaged kidney cells to ameliorate AKI. Consequently, many successful AKI biomarker findings and therapeutic applications based on EVs have been made. Here, we review our understanding of how EVs can help with the early identification and accurate monitoring of AKI and be used therapeutically. We will further discuss where current EV-based AKI diagnosis and therapeutic applications fall short and where future innovations could lead us.

Human MSC-Derived Exosomes Reduce Cellular Senescence in Renal Epithelial Cells

“…Previous studies have highlighted the potential of MSC and MSC-derived exosomes in delaying and even reversing kidney disease [51,52] and for improving outcomes after kidney transplantation [53,54]. While these studies have shown immune-modulatory, anti-fibrotic, anti-apoptotic, pro-regenerative and pro-angiogenic properties of MSC or their derivatives, only a few reports are available regarding their potential effects on cellular senescence.…”

Urinary extracellular vesicles and micro-RNA as markers of acute kidney injury after cardiac surgery

“…The EV are classi ed as microvesicles that bud off the plasma membrane or exosomes that are secreted through the exocytic pathway. EV contain proteins speci c for their origin; therefore, changes in speci c EV's concentration during pathological processes can point towards affected cells or tissues (reviewed in [7]).…”

Extracellular Vesicles That Herald the Scarcity of Oxygen

“…A delivery means specifically targeting the injured kidney cells, therefore, needs to be established. In this regard, extracellular vesicles (EVs) have emerged as a vehicle to achieve such renal injury-specific drug targeting, for these natural, membrane-bound nanoparticles can be engineered to transport desired drugs to the injury site with great precision and accuracy [3, 4].…”

“…Notably, this so-called ischemic preconditioning (IPC) state can be transferred from a donor to a recipient, inducing remote IPC [5, 6]. Present in various body fluids such as blood, saliva, and urine, EVs are known to carry a specific set of cargo molecules that mirror the physiological and pathological status of the producing cells, eventually discharging the contents in EV-receiving cells [3]. Indeed, EVs derived from a donor of IPC are known to mount remote IPC in recipients, presumably through delivering a select set of cargos that reflect the IPC state, to assist injured kidney cells to recover [7].…”

“…EVs have several favorable attributes as a drug delivery vehicle to target an injured tissue. Above all, EVs appear to be more biocompatible, less immunogenic, and more barrier-permeable, compared to other nanoscale particles [3]. A wide range of cargo molecules of potential therapeutic value have thus been examined whether they can be stably delivered via EVs [3].…”