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Extracellular Vesicles in Renal Diseases and Regeneration
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Extracellular Vesicles in Renal Diseases and Regeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 21524

Special Issue Editor

Dr. Stefania Bruno

E-Mail Website
Guest Editor
Department of Medical Sciences, Universita degli Studi di Torino, Torino, Italy
Interests: tissue regeneration; stem cells; extracellular vesicles; liver fibrosis; acute kidney injury; chronic kidney disease.
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are emerging as important players in cell-to-cell communication. EV content (RNAs and proteins) reflect the state of producing cells/tissues and can be modulated by different environmental factors. Increasing interest is aimed at the pro-regenerative effects of EVs of different origin in different in vitro and in vivo models of acute and chronic kidney disease. It has been shown that EVs from stem cells mimic the cells of origin and, once injected in vivo, improve renal function and morphology by inducing pro-regenerative program in cells survived to different types of injury. Moreover, it has been reported that urinary EVs can act in inter-nephron communication in physiological and pathological conditions.

The focus of this Special Issue will be, but not limited to:

- on the role of EVs in intra-renal communication

- on EVs as bio-markers of renal diseases

- on EVs as cell-free therapeutic agents

Dr. Stefania Bruno
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Research

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20 pages, 4628 KiB  
Article
Treatment of Chronic Kidney Disease with Extracellular Vesicles from Mesenchymal Stem Cells and CD133+ Expanded Cells: A Comparative Preclinical Analysis
by Dayane Mayumi Miyasaki, Alexandra Cristina Senegaglia, Sérgio Adriane Bezerra de Moura, Amanda Leitolis, Luiz Guilherme Achcar Capriglione, Letícia Fracaro, Lidiane Maria Boldrini Leite, Paulo Henrique Utumi, Felipe Yukio Ishikawa Fragoso, Fernando Meyer, Alejandro Correa and Paulo Roberto Slud Brofman
Int. J. Mol. Sci. 2022, 23(5), 2521; https://doi.org/10.3390/ijms23052521 - 25 Feb 2022
Cited by 9 | Viewed by 2428
Abstract
Chronic kidney disease (CKD) is characterized by structural abnormalities and the progressive loss of kidney function. Extracellular vesicles (EVs) from human umbilical cord tissue (hUCT)-derived mesenchymal stem cells (MSCs) and expanded human umbilical cord blood (hUCB)-derived CD133+ cells (eCD133+) maintain [...] Read more.
Chronic kidney disease (CKD) is characterized by structural abnormalities and the progressive loss of kidney function. Extracellular vesicles (EVs) from human umbilical cord tissue (hUCT)-derived mesenchymal stem cells (MSCs) and expanded human umbilical cord blood (hUCB)-derived CD133+ cells (eCD133+) maintain the characteristics of the parent cells, providing a new form of cell-free treatment. We evaluated the effects of EVs from hUCT-derived MSCs and hUCB-derived CD133+ cells on rats with CDK induced by an adenine-enriched diet. EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA) and electron microscopy. The animals were randomized and divided into the MSC-EV group, eEPC-EV group and control group. Infusions occurred on the seventh and 14th days after CKD induction. Evaluations of kidney function were carried out by biochemical and histological analyses. Intense labeling of the α-SMA protein was observed when comparing the control with MSC-EVs. In both groups treated with EVs, a significant increase in serum albumin was observed, and the increase in cystatin C was inhibited. The results indicated improvements in renal function in CKD, demonstrating the therapeutic potential of EVs derived from MSCs and eCD133+ cells and suggesting the possibility that in the future, more than one type of EV will be used concurrently. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Renal Diseases and Regeneration)
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Review

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28 pages, 2215 KiB  
Review
Extracellular Vesicles Released from Stem Cells as a New Therapeutic Strategy for Primary and Secondary Glomerulonephritis
by Marco Quaglia, Guido Merlotti, Laura Fornara, Andrea Colombatto and Vincenzo Cantaluppi
Int. J. Mol. Sci. 2022, 23(10), 5760; https://doi.org/10.3390/ijms23105760 - 20 May 2022
Cited by 4 | Viewed by 3032
Abstract
Current treatment of primary and secondary glomerulopathies is hampered by many limits and a significant proportion of these disorders still evolves towards end-stage renal disease. A possible answer to this unmet challenge could be represented by therapies with stem cells, which include a [...] Read more.
Current treatment of primary and secondary glomerulopathies is hampered by many limits and a significant proportion of these disorders still evolves towards end-stage renal disease. A possible answer to this unmet challenge could be represented by therapies with stem cells, which include a variety of progenitor cell types derived from embryonic or adult tissues. Stem cell self-renewal and multi-lineage differentiation ability explain their potential to protect and regenerate injured cells, including kidney tubular cells, podocytes and endothelial cells. In addition, a broad spectrum of anti-inflammatory and immunomodulatory actions appears to interfere with the pathogenic mechanisms of glomerulonephritis. Of note, mesenchymal stromal cells have been particularly investigated as therapy for Lupus Nephritis and Diabetic Nephropathy, whereas initial evidence suggest their beneficial effects in primary glomerulopathies such as IgA nephritis. Extracellular vesicles mediate a complex intercellular communication network, shuttling proteins, nucleic acids and other bioactive molecules from origin to target cells to modulate their functions. Stem cell-derived extracellular vesicles recapitulate beneficial cytoprotective, reparative and immunomodulatory properties of parental cells and are increasingly recognized as a cell-free alternative to stem cell-based therapies for different diseases including glomerulonephritis, also considering the low risk for potential adverse effects such as maldifferentiation and tumorigenesis. We herein summarize the renoprotective potential of therapies with stem cells and extracellular vesicles derived from progenitor cells in glomerulonephritis, with a focus on their different mechanisms of actions. Technological progress and growing knowledge are paving the way for wider clinical application of regenerative medicine to primary and secondary glomerulonephritis: this multi-level, pleiotropic therapy may open new scenarios overcoming the limits and side effects of traditional treatments, although the promising results of experimental models need to be confirmed in the clinical setting. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Renal Diseases and Regeneration)
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18 pages, 8692 KiB  
Review
Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases
by Giulia Cricrì, Linda Bellucci, Giovanni Montini and Federica Collino
Int. J. Mol. Sci. 2021, 22(12), 6507; https://doi.org/10.3390/ijms22126507 - 17 Jun 2021
Cited by 23 | Viewed by 3627
Abstract
Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell [...] Read more.
Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier—or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Renal Diseases and Regeneration)
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18 pages, 687 KiB  
Review
Extracellular Vesicles as a Therapeutic Tool for Kidney Disease: Current Advances and Perspectives
by Raphael Rodrigues Corrêa, Estela Mancheño Juncosa, Rosalinde Masereeuw and Rafael Soares Lindoso
Int. J. Mol. Sci. 2021, 22(11), 5787; https://doi.org/10.3390/ijms22115787 - 28 May 2021
Cited by 19 | Viewed by 3839
Abstract
Extracellular vesicles (EVs) have been described as important mediators of cell communication, regulating several physiological processes, including tissue recovery and regeneration. In the kidneys, EVs derived from stem cells have been shown to support tissue recovery in diverse disease models and have been [...] Read more.
Extracellular vesicles (EVs) have been described as important mediators of cell communication, regulating several physiological processes, including tissue recovery and regeneration. In the kidneys, EVs derived from stem cells have been shown to support tissue recovery in diverse disease models and have been considered an interesting alternative to cell therapy. For this purpose, however, several challenges remain to be overcome, such as the requirement of a high number of EVs for human therapy and the need for optimization of techniques for their isolation and characterization. Moreover, the kidney’s complexity and the pathological process to be treated require that EVs present a heterogeneous group of molecules to be delivered. In this review, we discuss the recent advances in the use of EVs as a therapeutic tool for kidney diseases. Moreover, we give an overview of the new technologies applied to improve EVs’ efficacy, such as novel methods of EV production and isolation by means of bioreactors and microfluidics, bioengineering the EV content and the use of alternative cell sources, including kidney organoids, to support their transfer to clinical applications. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Renal Diseases and Regeneration)
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20 pages, 1137 KiB  
Review
Extracellular Vesicles Tune the Immune System in Renal Disease: A Focus on Systemic Lupus Erythematosus, Antiphospholipid Syndrome, Thrombotic Microangiopathy and ANCA-Vasculitis
by Martina Mazzariol, Giovanni Camussi and Maria Felice Brizzi
Int. J. Mol. Sci. 2021, 22(8), 4194; https://doi.org/10.3390/ijms22084194 - 18 Apr 2021
Cited by 12 | Viewed by 3394
Abstract
Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. [...] Read more.
Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. The ability of EV to modulate the immune system, the coagulation cascade, the angiogenetic process, and to drive endothelial dysfunction plays a crucial role in the pathophysiology of both autoimmune and renal diseases. Recent studies have demonstrated the involvement of EV in the control of renal homeostasis by acting as intercellular signaling molecules, mediators of inflammation and tissue regeneration. Moreover, circulating EV and urinary EV secreted by renal cells have been investigated as potential early biomarkers of renal injury. In the present review, we discuss the recent findings on the involvement of EV in autoimmunity and in renal intercellular communication. We focused on EV-mediated interaction between the immune system and the kidney in autoimmune diseases displaying common renal damage, such as antiphospholipid syndrome, systemic lupus erythematosus, thrombotic microangiopathy, and vasculitis. Although further studies are needed to extend our knowledge on EV in renal pathology, a deeper investigation of the impact of EV in kidney autoimmune diseases may also provide insight into renal biological processes. Furthermore, EV may represent promising biomarkers of renal diseases with potential future applications as diagnostic and therapeutic tools. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Renal Diseases and Regeneration)
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19 pages, 9745 KiB  
Review
Extracellular Vesicles and Renal Fibrosis: An Odyssey toward a New Therapeutic Approach
by Maja Kosanović, Alicia Llorente, Sofija Glamočlija, José M. Valdivielso and Milica Bozic
Int. J. Mol. Sci. 2021, 22(8), 3887; https://doi.org/10.3390/ijms22083887 - 09 Apr 2021
Cited by 7 | Viewed by 4384
Abstract
Renal fibrosis is a complex disorder characterized by the destruction of kidney parenchyma. There is currently no cure for this devastating condition. Extracellular vesicles (EVs) are membranous vesicles released from cells in both physiological and diseased states. Given their fundamental role in transferring [...] Read more.
Renal fibrosis is a complex disorder characterized by the destruction of kidney parenchyma. There is currently no cure for this devastating condition. Extracellular vesicles (EVs) are membranous vesicles released from cells in both physiological and diseased states. Given their fundamental role in transferring biomolecules to recipient cells and their ability to cross biological barriers, EVs have been widely investigated as potential cell-free therapeutic agents. In this review, we provide an overview of EVs, focusing on their functional role in renal fibrosis and signaling messengers responsible for EV-mediated crosstalk between various renal compartments. We explore recent findings regarding the renoprotective effect of EVs and their use as therapeutic agents in renal fibrosis. We also highlight advantages and future perspectives of the therapeutic applications of EVs in renal diseases. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Renal Diseases and Regeneration)
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