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      Exosomes in Nephropathies: A Rich Source of Novel Biomarkers

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          Abstract

          The biomarkers commonly utilized in diagnostic evaluations of kidney disease suffer from low sensitivity, especially in the early stages of renal damage. On the other hand, obtaining a renal biopsy to augment clinical decision making can lead to potentially serious complications. In order to overcome the shortcomings of currently available diagnostic tools, recent studies suggest that exosomes, cell-secreted extracellular vesicles containing a large array of active molecules to facilitate cell-to-cell communication, may represent a rich source of novel disease biomarkers. Because of their endocytic origin, exosomes carry markers typical for their parent cells, which could permit the localization of biochemical cellular alterations in specific kidney compartments. Different types of exosomes can be isolated from noninvasively obtained biofluids; however, in the context of kidney disease, evidence has emerged on the role of urinary exosomes in the diagnostic and predictive modeling of renal pathology. The current review summarizes the potential application of exosomes in the detection of acute and chronic inflammatory, metabolic, degenerative, and genetic renal diseases.

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          Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics

          Exosomes are small extracellular vesicles with diameters of 30-150 nm. In both physiological and pathological conditions, nearly all types of cells can release exosomes, which play important roles in cell communication and epigenetic regulation by transporting crucial protein and genetic materials such as miRNA, mRNA, and DNA. Consequently, exosome-based disease diagnosis and therapeutic methods have been intensively investigated. However, as in any natural science field, the in-depth investigation of exosomes relies heavily on technological advances. Historically, the two main technical hindrances that have restricted the basic and applied researches of exosomes include, first, how to simplify the extraction and improve the yield of exosomes and, second, how to effectively distinguish exosomes from other extracellular vesicles, especially functional microvesicles. Over the past few decades, although a standardized exosome isolation method has still not become available, a number of techniques have been established through exploration of the biochemical and physicochemical features of exosomes. In this work, by comprehensively analyzing the progresses in exosome separation strategies, we provide a panoramic view of current exosome isolation techniques, providing perspectives toward the development of novel approaches for high-efficient exosome isolation from various types of biological matrices. In addition, from the perspective of exosome-based diagnosis and therapeutics, we emphasize the issue of quantitative exosome and microvesicle separation.
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            Large-scale proteomics and phosphoproteomics of urinary exosomes.

            Normal human urine contains large numbers of exosomes, which are 40- to 100-nm vesicles that originate as the internal vesicles in multivesicular bodies from every renal epithelial cell type facing the urinary space. Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously, including 177 that are represented on the Online Mendelian Inheritance in Man database of disease-related genes, suggesting that exosome analysis is a potential approach to discover urinary biomarkers. We extended the proteomic analysis to phosphoproteomic profiling using neutral loss scanning, and this yielded multiple novel phosphorylation sites, including serine-811 in the thiazide-sensitive Na-Cl co-transporter, NCC. To demonstrate the potential use of exosome analysis to identify a genetic renal disease, we carried out immunoblotting of exosomes from urine samples of patients with a clinical diagnosis of Bartter syndrome type I, showing an absence of the sodium-potassium-chloride co-transporter 2, NKCC2. The proteomic data are publicly accessible at http://dir.nhlbi.nih.gov/papers/lkem/exosome/.
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              Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases

              Background Bio-products from stem/progenitor cells, such as extracellular vesicles, are likely a new promising approach for reprogramming resident cells in both acute and chronic kidney disease. Forty CKD patients stage III and IV (eGFR 15–60 mg/ml) have been divided into two groups; twenty patients as treatment group “A” and twenty patients as a matching placebo group “B”. Two doses of MSC-derived extracellular vesicles had been administered to patients of group “A”. Blood urea, serum creatinine, urinary albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used to assess kidney functions and TNF-α, TGF-β1 and IL-10 have been used to assess the amelioration of the inflammatory immune activity. Results Participants in group A exhibited significant improvement of eGFR, serum creatinine level, blood urea and UACR. Patients of the treatment group “A” also exhibited significant increase in plasma levels of TGF-β1, and IL-10 and significant decrease in plasma levels of TNF-α. Participants of the control group B did not show significant improvement in any of the previously mentioned parameters at any time point of the study period. Conclusion Administration of cell-free cord-blood mesenchymal stem cells derived extracellular vesicles (CF-CB-MSCs-EVs) is safe and can ameliorate the inflammatory immune reaction and improve the overall kidney function in grade III-IV CKD patients.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2020
                12 August 2020
                : 2020
                : 8897833
                Affiliations
                1First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias street, Bld 10, Goudi, 11527 Athens, Greece
                2Children's National Hospital, Division of Emergency Medicine and Center for Genetic Medicine, George Washington University School of Medicine and Health Sciences, 111 Michigan Ave. NW, Washington, DC 20010, USA
                Author notes

                Academic Editor: Wen-Jun Tu

                Author information
                https://orcid.org/0000-0002-0930-1657
                Article
                10.1155/2020/8897833
                7441435
                2b76e4e4-814c-40d5-b1dc-a8b0306b1d59
                Copyright © 2020 Christos Masaoutis et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 April 2020
                : 8 July 2020
                : 24 July 2020
                Categories
                Review Article

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