Extracellular Vesicles as Theranostic Tools in Kidney Disease

Abstract

Extracellular vesicles are important vectors for cell-cell communication and show potential value for diagnosis and treatment of kidney diseases. The pathologic diagnosis of kidney diseases relies on kidney biopsy, whereas collection of extracellular vesicles from urine or circulating blood may constitute a less invasive diagnostic tool. In particular, urinary extracellular vesicles released mainly from resident kidney cells might provide an alternative tool for detection of kidney injury. Because extracellular vesicles mirror many features of their parent cells, cargoes of several populations of urinary extracellular vesicle are promising biomarkers for disease processes like diabetic kidney disease, kidney transplant, and lupus nephritis. Contrarily, extracellular vesicles derived from reparative cells, such as mesenchymal stem cells, tubular epithelial progenitor cells, and human umbilical cord blood represent promising regenerative tools for treatment of kidney diseases. Furthermore, induced pluripotent stem cell-derived and engineered extracellular vesicles are being developed for specific applications for the kidney. Nevertheless, some assumptions regarding the specificity and immunogenicity of extracellular vesicles remain to be established. This review focuses on the utility of extracellular vesicles as therapeutic and diagnostic (theranostic) tools in kidney diseases and future directions for studies.

Extracellular Vesicles in Kidney Diseases: Moving Forward

“…EVs from different types of stem cells, their routes of administration and also mechanism of actions have been studied [2]. Very recently uEVs have been found to be protective in a glycerol induced AKI model, in which Klotho might serve a function in regeneration [56](for review see [57], [2], [6], [58]).…”

“…EVs from different types of stem cells, their routes of administration, and also mechanism of actions have been studied. 2 Very recently uEVs have been found to be protective in a glycerol-induced AKI model, in which Klotho might serve a function in regeneration 72 (for review, see 2,7,8,73 ). Significant progress has been made to understand the regenerative role of EVs in AKI and CKD, but still many challenges exist to understand the EV types and optimal techniques in isolation, storage, and preparation to guarantee safety and minimize possible long-term side effects of EV therapeutics in AKI.…”

“…We will then discuss the ever-evolving understanding of EVs' role in major clinical syndromes, from acute kidney injury (AKI) to chronic kidney disease (CKD), and from glomerular to tubular disease. EVs' therapeutic role has been reviewed extensively elsewhere and we refer the readers to those publications [2], [1], [6], [58]. We will end this review with a critical look whether EVs live up to their expectations and which barriers still need to be overcome.…”

“…EVs' therapeutic role has been reviewed extensively elsewhere, and we refer the readers to those publications. 1,2,7,8 We will end this review with a critical look whether EVs live up to their expectations and which barriers still need to be overcome. studies discussed.…”

Urinary extracellular vesicles and tubular transport

“…To decrease and ultimately overcome the issue of variability among uEV studies, guidelines for reporting on isolation, characterization, and normalization have been developed by EV-TRACK (evtrack.org) and the Urinary Task Force of the International Society for Extracellular Vesicles [1,12]. Recent reviews have covered uEV biomarkers in other kidney diseases and kidney transplantation as well the therapeutic use of EVs [13,14]. Here, we review which tubular transporters have been identified and characterized in uEVs, how EVs may regulate tubular transporters, and whether uEV cargo may reveal disease mechanisms and serve as biomarkers for kidney disease and hypertension.…”