scholarly journals Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6507
Author(s):  
Giulia Cricrì ◽  
Linda Bellucci ◽  
Giovanni Montini ◽  
Federica Collino
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Diagnostic Techniques ◽  
Cell Contact ◽  
Glomerular Filtration Barrier ◽  
Alternative Source ◽  
Filtration Barrier ◽  
Multicellular Interactions ◽  
Almost All ◽  
Cell Crosstalk

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.

scholarly journals Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves

2019 ◽  
Author(s):  
Benedikt Kirchner ◽  
Dominik Buschmann ◽  
Vijay Paul ◽  
Michael W. Pfaffl
Keyword(s):  
Extracellular Vesicles ◽  
Expression Profiles ◽  
Bovine Milk ◽  
Cell Types ◽  
Specific Protein ◽  
In Vivo Experiments ◽  
Neonatal Calves ◽  
Almost All

Abstract Background Extracellular vesicles (EVs) such as exosomes are key regulators of intercellular communication that can be found in almost all bio fluids. Although studies in the last decade have made great headway in discerning the role of EVs in many physiological and pathophysiological processes, the bioavailability and impact of dietary EVs and their cargo still remain to be elucidated. Due to its widespread consumption and high content of EV-associated microRNAs and proteins, a major focus in this field has been set on EVs in bovine milk and colostrum. Despite promising in vitro studies in recent years that show high resiliency of milk EVs to degradation and uptake of milk EV cargo in a variety of intestinal and blood cell types, in vivo experiments continue to be inconclusive and sometimes outright contradictive. Results To resolve this discrepancy, we assessed the potential postprandial transfer of colostral EVs to the circulation of newborn calves by analysing colostrum-specific protein and miRNAs, including specific isoforms (isomiRs) in cells, EV isolations and unfractionated samples from blood and colostrum. Our findings reveal distinct populations of EVs in colostrum and blood from cows that can be clearly separated by density, particle concentration and protein content (BTN1A1, MFGE8). Postprandial blood samples of calves show a time-dependent increase in EVs that share morphological and protein characteristics of colostral EVs. Analysis of miRNA expression profiles by Next-Generation Sequencing gave a different picture however. Although significant postprandial expression changes could only be detected for calf EV samples, expression profiles show very limited overlap with highly expressed miRNAs in colostral EVs or colostrum in general. Conclusions Taken together our results indicate a selective uptake of membrane-associated protein cargo but not luminal miRNAs from colostral EVs into the circulation of neonatal calves.

The renal glomerulus

2015 ◽  
Author(s):  
Marlies Elger ◽  
Wilhelm Kriz
Keyword(s):  
Epithelial Cells ◽  
Mesangial Cells ◽  
Juxtaglomerular Apparatus ◽  
Cell Types ◽  
Stem Cell Population ◽  
Glomerular Filtration Barrier ◽  
Crescent Formation ◽  
Filtration Barrier ◽  
Parietal Epithelial Cells ◽  
Bowman's Capsule

The glomerulus performs its functions with three major cell types. Endothelial cells and visceral epithelial cells (podocytes) lie on the inside and outside of the glomerular basement membrane, and together these three structures form the glomerular filtration barrier. Mesangial cells sit in the axial region. Pathologies of all these regions and cell types can be identified. Parietal epithelial cells lining Bowman’s capsule participate in crescent formation, and at the tubular pole some of these cells seem to represent a stem cell population for tubular cells and podocytes. The extraglomerular mesangium and juxtaglomerular apparatus complete the description of the glomerular corpuscle. The structure of these elements, and how they relate to function, are illustrated in detail.

scholarly journals Stem Cell-Derived Extracellular Vesicles for Treating Joint Injury and Osteoarthritis

Nanomaterials ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 261 ◽  
Author(s):  
Jiao Li ◽  
Elham Hosseini-Beheshti ◽  
Georges Grau ◽  
Hala Zreiqat ◽  
Christopher Little
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Joint Injury ◽  
Direct Cell ◽  
Almost All ◽  
New Treatments

Extracellular vesicles (EVs) are nanoscale particles secreted by almost all cell types to facilitate intercellular communication. Stem cell-derived EVs theoretically have the same biological functions as stem cells, but offer the advantages of small size, low immunogenicity, and removal of issues such as low cell survival and unpredictable long-term behaviour associated with direct cell transplantation. They have been an area of intense interest in regenerative medicine, due to the potential to harness their anti-inflammatory and pro-regenerative effects to induce healing in a wide variety of tissues. However, the potential of using stem cell-derived EVs for treating joint injury and osteoarthritis has not yet been extensively explored. The pathogenesis of osteoarthritis, with or without prior joint injury, is not well understood, and there is a longstanding unmet clinical need to develop new treatments that provide a therapeutic effect in preventing or stopping joint degeneration, rather than merely relieving the symptoms of the disease. This review summarises the current evidence relating to stem cell-derived EVs in joint injury and osteoarthritis, providing a concise discussion of their characteristics, advantages, therapeutic effects, limitations and outlook in this exciting new area.

scholarly journals Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans

2016 ◽  
Vol 40 (5) ◽  
pp. 819-830 ◽  
Author(s):  
Janina Müller-Deile ◽  
Finn Gellrich ◽  
Heiko Schenk ◽  
Patricia Schroder ◽  
Jenny Nyström ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Glomerular Filtration ◽  
Cell Types ◽  
Endothelial Damage ◽  
Micro Rna ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Glomerular Endothelial Cells ◽  
Apoptotic Pathways

Background: TGF-β is known as an important stress factor of podocytes in glomerular diseases. Apart from activation of direct pro-apoptotic pathways we wanted to analyze micro-RNA (miRs) driven regulation of components involved in the integrity of the glomerular filtration barrier induced by TGF-β. Since miR-143-3p (miR-143) is described as a TGF-β inducible miR in other cell types, we examined this specific miR and its ability to induce glomerular pathology. Methods: We analyzed miR-143 expression in cultured human podocytes after stimulation with TGF-β. We also microinjected zebrafish eggs with a miR-143 mimic or with morpholinos specific for its targets syndecan and versican and compared phenotype and proteinuria development. Results: We detected a time dependent, TGF-β inducible expression of miR-143 in human podocytes. Targets of miR-143 relevant in glomerular biology are syndecans and versican, which are known components of the glycocalyx. We found that syndecan 1 and 4 were predominantly expressed in podocytes while syndecan 3 was largely expressed in glomerular endothelial cells. Versican could be detected in both cell types. After injection of a miR-143 mimic in zebrafish larvae, syndecan 3, 4 and versican were significantly downregulated. Moreover, miR-143 overexpression or versican knockdown by morpholino caused loss of plasma proteins, edema, podocyte effacement and endothelial damage. In contrast, knockdown of syndecan 3 and syndecan 4 had no effects on glomerular filtration barrier. Conclusion: Expression of versican and syndecan isoforms is indispensable for proper barrier function. Podocyte-derived miR-143 is a mediator for paracrine and autocrine cross talk between podocytes and glomerular endothelial cells and can alter expression of glomerular glycocalyx proteins.

scholarly journals Extracellular Vesicles and Their Relationship with the Heart–Kidney Axis, Uremia and Peritoneal Dialysis

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 778
Author(s):  
Carolina Amaral Bueno Azevedo ◽  
Regiane Stafim da Cunha ◽  
Carolina Victoria Cruz Junho ◽  
Jessica Verônica da Silva ◽  
Andréa N. Moreno-Amaral ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Extracellular Vesicles ◽  
Cardiorenal Syndrome ◽  
Cell Types ◽  
Renal Tissue ◽  
Uremic Toxin ◽  
Home Based ◽  
Stage Renal Disease ◽  
Almost All ◽  
End Stage

Cardiorenal syndrome (CRS) is described as primary dysfunction in the heart culminating in renal injury or vice versa. CRS can be classified into five groups, and uremic toxin (UT) accumulation is observed in all types of CRS. Protein-bound uremic toxin (PBUT) accumulation is responsible for permanent damage to the renal tissue, and mainly occurs in CRS types 3 and 4, thus compromising renal function directly leading to a reduction in the glomerular filtration rate (GFR) and/or subsequent proteinuria. With this decrease in GFR, patients may need renal replacement therapy (RRT), such as peritoneal dialysis (PD). PD is a high-quality and home-based dialysis therapy for patients with end-stage renal disease (ESRD) and is based on the semi-permeable characteristics of the peritoneum. These patients are exposed to factors which may cause several modifications on the peritoneal membrane. The presence of UT may harm the peritoneum membrane, which in turn can lead to the formation of extracellular vesicles (EVs). EVs are released by almost all cell types and contain lipids, nucleic acids, metabolites, membrane proteins, and cytosolic components from their cell origin. Our research group previously demonstrated that the EVs can be related to endothelial dysfunction and are formed when UTs are in contact with the endothelial monolayer. In this scenario, this review explores the mechanisms of EV formation in CRS, uremia, the peritoneum, and as potential biomarkers in peritoneal dialysis.

Molecular basis of nephrotic syndrome

2018 ◽  
Author(s):  
Moin A. Saleem ◽  
Corinne Antignac
Keyword(s):  
Nephrotic Syndrome ◽  
Basement Membrane ◽  
Molecular Basis ◽  
Great Majority ◽  
Genetic Associations ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Basement Membrane Protein ◽  
Podocyte Proteins ◽  
Almost All

Nephrotic syndrome is broadly a disorder of the glomerular filtration barrier, but in practice the site of dysfunction in the great majority of pathologies is in the podocyte. Genetic causes of nephrotic syndrome provide the strongest proof of this. Almost all the genetic associations with nephrotic syndrome are podocyte proteins. Some basement membrane protein mutations associated with nephrotic syndrome may act through signalling to podocytes, or by causing severe disruption to their environment.

Extracellular Vesicles Isolated from Mesenchymal Stromal Cells Primed with Hypoxia: Novel strategy in Regenerative Medicine

2020 ◽  
Vol 15 ◽  
Author(s):  
Shalmali Pendse ◽  
Vaijayanti Kale ◽  
Anuradha Vaidya
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Cell Types ◽  
Molecular Profile ◽  
Cell Contact ◽  
Hematopoietic Stem

: Mesenchymal stromal cells (MSCs) regulate other cell types through a strong paracrine component called the secretome, comprising of several bioactive entities. The composition of the MSCs’ secretome is dependent upon the microenvironment in which they thrive, and hence, it could be altered by pre-conditioning the MSCs during in vitro culture. The primary aim of this review is to discuss various strategies that are being used for pre-conditioning of MSCs, also known as “priming of MSCs”, in the context of improving their therapeutic potential. Several studies have underscored the importance of extracellular vesicles (EVs) derived from primed MSCs in improving their efficacy in the treatment of various diseases. We have previously shown that co-culturing hematopoietic stem cells (HSCs) with hypoxiaprimed MSCs improves their engraftment potential. Now the question we pose is would priming of MSCs with hypoxiafavorably alter theirsecretome and would this altered secretome work as effectively as the cell to cell contact did? Here we review the current strategies of using the secretome, specifically the EVs (microvesicles and exosomes), collected from the primed MSCs with the intention of expanding HSCs ex vivo. We speculate that an effective priming of MSCs in vitrocould modulate the molecular profile of their secretome, which could eventually be used as a cell-free biologic in clinical settings.

scholarly journals Tumor-Derived Extracellular Vesicles: A Means of Co-opting Macrophage Polarization in the Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Theodore Reed ◽  
Jeffrey Schorey ◽  
Crislyn D’Souza-Schorey
Keyword(s):  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Immune Modulation ◽  
Macrophage Polarization ◽  
Cell Types ◽  
Heterogeneous Population ◽  
Functional Plasticity ◽  
Bioactive Proteins ◽  
Membrane Bound ◽  
Almost All

Extracellular vesicles (EVs) are a heterogeneous population of membrane-bound parcels of bioactive proteins, nucleic acids, and lipids released from almost all cell types. The diversity of cargo packaged into EVs proffer the induction of an array of effects on recipient cells. EVs released from tumor cells have emerged as a vital means of communication and immune modulation within the tumor microenvironment (TME). Macrophages are an important contributor to the TME with seemingly paradoxical roles promoting either pro- or anti-tumoral immune function depending on their activated phenotypes. Here, we discuss the influence of tumor-derived extracellular vesicles on the functional plasticity of macrophages in tumor progression.

scholarly journals Targeting Extracellular Vesicles to Dendritic Cells and Macrophages

Acta Naturae ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 114-121
Author(s):  
Leyla A. Ovchinnikova ◽  
Ioanna N. Filimonova ◽  
Maria Y. Zakharova ◽  
Dmitriy S. Balabashin ◽  
Teimour K. Aliev ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Targeted Delivery ◽  
Protein Delivery ◽  
Cell Types ◽  
Modern Medicine ◽  
Virus Protein ◽  
Cargo Delivery ◽  
Oncological Diseases ◽  
Enhance Efficiency ◽  
Almost All

Targeting protein therapeutics to specific cells and tissues is a major challenge in modern medicine. Improving the specificity of protein therapeutic delivery will significantly enhance efficiency in drug development. One of the promising tools for protein delivery is extracellular vesicles (EVs) that are enveloped by a complex lipid bilayer. EVs are secreted by almost all cell types and possess significant advantages: biocompatibility, stability, and the ability to penetrate the bloodbrain barrier. Overexpression of the vesicular stomatitis virus protein G (VSV-G) was shown to promote EV formation by the producer cell. We have developed an EV-based system for targeted delivery of protein cargoes to antigen-presenting cells (APCs). In this study, we show that attachment of a recombinant llama nanobody -CD206 to the N-terminus of a truncated VSV-G increases the selectivity of EV cargo delivery mainly to APCs. These results highlight the outstanding technological and biomedical potential of EV-based delivery systems for correcting the immune response in patients with autoimmune, viral, and oncological diseases.

scholarly journals Extracellular Vesicles in Modifying the Effects of Ionizing Radiation

2019 ◽  
Vol 20 (22) ◽  
pp. 5527 ◽  
Author(s):  
Tünde Szatmári ◽  
Rita Hargitai ◽  
Géza Sáfrány ◽  
Katalin Lumniczky
Keyword(s):  
Ionizing Radiation ◽  
Extracellular Vesicles ◽  
Radiation Effects ◽  
Cell Types ◽  
Tumor Formation ◽  
The Body ◽  
Target Cells ◽  
Cell Of Origin ◽  
Radiation Induced ◽  
Almost All

Extracellular vesicles (EVs) are membrane-coated nanovesicles actively secreted by almost all cell types. EVs can travel long distances within the body, being finally taken up by the target cells, transferring information from one cell to another, thus influencing their behavior. The cargo of EVs comprises of nucleic acids, lipids, and proteins derived from the cell of origin, thereby it is cell-type specific; moreover, it differs between diseased and normal cells. Several studies have shown that EVs have a role in tumor formation and prognosis. It was also demonstrated that ionizing radiation can alter the cargo of EVs. EVs, in turn can modulate radiation responses and they play a role in radiation-induced bystander effects. Due to their biocompatibility and selective targeting, EVs are suitable nanocarrier candidates of drugs in various diseases, including cancer. Furthermore, the cargo of EVs can be engineered, and in this way they can be designed to carry certain genes or even drugs, similar to synthetic nanoparticles. In this review, we describe the biological characteristics of EVs, focusing on the recent efforts to use EVs as nanocarriers in oncology, the effects of EVs in radiation therapy, highlighting the possibilities to use EVs as nanocarriers to modulate radiation effects in clinical applications.

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