Extracellular Vesicles and Acute Kidney Injury: Potential Therapeutic Avenue for Renal Repair and Regeneration

Abstract

Acute kidney injury (AKI) is a sudden decline of renal function and represents a global clinical problem due to an elevated morbidity and mortality. Despite many efforts, currently there are no treatments to halt this devastating condition. Extracellular vesicles (EVs) are nanoparticles secreted by various cell types in both physiological and pathological conditions. EVs can arise from distinct parts of the kidney and can mediate intercellular communication between various cell types along the nephron. Besides their potential as diagnostic tools, EVs have been proposed as powerful new tools for regenerative medicine and have been broadly studied as therapeutic mediators in different models of experimental AKI. In this review, we present an overview of the basic features and biological relevance of EVs, with an emphasis on their functional role in cell-to-cell communication in the kidney. We explore versatile roles of EVs in crucial pathophysiological mechanisms contributing to AKI and give a detailed description of the renoprotective effects of EVs from different origins in AKI. Finally, we explain known mechanisms of action of EVs in AKI and provide an outlook on the potential clinical translation of EVs in the setting of AKI.

The effect of 2D culture on stemness-related transcriptome in shed microvesicles of mesenchymal stem cells

“…For indirect inspection of 10-day cultured MSCs, their shed MVs were isolated. Characterization of isolated MVs from MSCs, including shape, diameter, and size distribution (Figure 3) was in accordance with previous studies [32,33]. There are few studies about the mRNA, miRNA, and protein contents of MVs.…”

“…Xie, et al reported regulation of hematopoiesis by miRNAs in MSCs-derived MVs applied in ex vivo expansion of cord blood mononuclear cells [33]. In another study, MSCs-derived MVs enhanced the survival of renal cells both in vitro and in vivo [32]. Herein some stemness markers such as OCT4 and ALP [34] were evaluated.…”

Understanding exosomes: Part 2—Emerging leaders in regenerative medicine

“…In addition to their therapeutic possibilities, exosomes have also been studied for their potential as biomarkers for the identification of AKI 527 . A research paper titled: “Unconscious Cells and Sudden Kidney Damage: Potential Therapeutic Avenue for Renal Repair and Regeneration” 528 highlighted the effects of exosomes and how they affect multiple pathways of tissue regeneration including their role in (1) attenuating inflammation and improving immune modulation, (2) aiding in cell proliferation, (3) improving oxidative stress, (4) autophagy, and (5) minimizing cell death. Multiple lines of evidence substantiate the renoprotective impact of EVs derived from various sources in mitigating renal injury in diverse experimental models of AKI as presented in Table 16 528 …”

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

“…Exosomes (30–150 nm) originate through the invagination of the limiting membrane of the early endosome, i.e., multivesicular bodies (MVBs) and are released to the extracellular environment upon fusion of MVBs with the plasma membrane [ 5 ]. Microvesicles (MVs) (100–1000 nm) are produced by outward budding and pinching of the plasma membrane [ 8 , 9 ]. The intracellular membrane is not involved during the secretion of microvesicles, and thus the membrane composition closely mirrors that of parent cells, a key difference from exosomes, which are heavily enriched in phosphatidylserine [ 4 ].…”