scholarly journals Therapeutic Potential of Extracellular Vesicles in Hypertension-Associated Kidney Disease

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 28-38
Author(s):  
Olga Martinez-Arroyo ◽  
Ana Ortega ◽  
Josep Redon ◽  
Raquel Cortes
Keyword(s):  
Kidney Disease ◽  
Extracellular Vesicles ◽  
Renal Damage ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Cell Types ◽  
Organ Damage ◽  
Renal Diseases ◽  
Biological Processes ◽  
Potential Use

Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases.

scholarly journals Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

2020 ◽  
Vol 21 (15) ◽  
pp. 5432 ◽  
Author(s):  
Stefano Burgio ◽  
Leila Noori ◽  
Antonella Marino Gammazza ◽  
Claudia Campanella ◽  
Mariantonia Logozzi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Delivery System ◽  
Malignant Pleural Mesothelioma ◽  
Cell Communication ◽  
Cell Types ◽  
Delivery Systems ◽  
Pleural Mesothelioma ◽  
Potential Use

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

scholarly journals Anti-Cancer Role and Therapeutic Potential of Extracellular Vesicles

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6303
Author(s):  
Naoomi Tominaga
Keyword(s):  
Extracellular Vesicles ◽  
Drug Delivery Systems ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Cancer Therapeutics ◽  
Nanometer Scale ◽  
Biological Processes ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Cell Cell

Cell–cell communication is an important mechanism in biological processes. Extracellular vesicles (EVs), also referred to as exosomes, microvesicles, and prostasomes, are microvesicles secreted by a variety of cells. EVs are nanometer-scale vesicles composed of a lipid bilayer and contain biological functional molecules, such as microRNAs (miRNAs), mRNAs, and proteins. In this review, “EVs” is used as a comprehensive term for vesicles that are secreted from cells. EV research has been developing over the last four decades. Many studies have suggested that EVs play a crucial role in cell–cell communication. Importantly, EVs contribute to cancer malignancy mechanisms such as carcinogenesis, proliferation, angiogenesis, metastasis, and escape from the immune system. EVs derived from cancer cells and their microenvironments are diverse, change in nature depending on the condition. As EVs are thought to be secreted into body fluids, they have the potential to serve as diagnostic markers for liquid biopsy. In addition, cells can encapsulate functional molecules in EVs. Hence, the characteristics of EVs make them suitable for use in drug delivery systems and novel cancer treatments. In this review, the potential of EVs as anti-cancer therapeutics is discussed.

scholarly journals Origins to Outcomes: A Role for Extracellular Vesicles in Precision Medicine

2018 ◽  
Vol 1 (1) ◽  
pp. 18-42 ◽  
Author(s):  
John Savage ◽  
Ciaran Manus Maguire ◽  
Adrielle Prina-Mello
Keyword(s):  
Precision Medicine ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Disease Diagnosis ◽  
Biological Research ◽  
Biological Processes ◽  
Therapeutic Approaches ◽  
Recent Developments ◽  
Almost All

Extracellular vesicles (EVs) are of great interest in biological research, and though they are a relatively recent discovery, they have rapidly shown great potential for use in clinical applications. The various techniques used in EV isolation along with their respective strengths, weaknesses, and potential for downstream applications are outlined here. A brief description of the different approaches in exosome characterisation are subsequently described. It has been highlighted that despite the recent developments in these processes, there is still a great deal of refinement to be made. EVs are produced by almost all cell types, found in many biological samples, and are implicated in multiple biological processes including cargo trafficking, cell-cell communication, and signal transduction. The presence of these EVs and their varied cargo in a biological sample can be indicative in disease diagnosis, and guide precision medicine-based approaches to disease management. EVs have been reported to actin the benefit of the cell through moderating repair and regeneration, but they can also act to the detriment of the cell through increased tumorigenesis and metastasis. This duality is intriguing as it can allow for the use of EVs in distinct therapeuticapproaches and displays their versatility in potential downstream applications. In this review, examples of the cellular roles of EVs and their applications in pathological and regenerative contexts are explored. In reviewing some of the developments madein recent times, EVs are shown to be very promising both in diagnostic and therapeutic approaches.

scholarly journals Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

2021 ◽  
Vol 10 (10) ◽  
pp. 2046
Author(s):  
Goren Saenz-Pipaon ◽  
Saioa Echeverria ◽  
Josune Orbe ◽  
Carmen Roncal
Keyword(s):  
Kidney Disease ◽  
Extracellular Vesicles ◽  
Diabetic Kidney Disease ◽  
Current Knowledge ◽  
Developed Countries ◽  
Disease Diagnosis ◽  
Renal Diseases ◽  
Diabetic Kidney ◽  
Glucose Levels ◽  
Stage Renal Disease

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.

scholarly journals Extracellular vesicles and exosomes generated from cystic renal epithelial cells promote cyst growth in autosomal dominant polycystic kidney disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hao Ding ◽  
Linda Xiaoyan Li ◽  
Peter C. Harris ◽  
Junwei Yang ◽  
Xiaogang Li
Keyword(s):  
Kidney Disease ◽  
Epithelial Cells ◽  
Polycystic Kidney Disease ◽  
Extracellular Vesicles ◽  
Autosomal Dominant ◽  
Therapeutic Potential ◽  
Polycystic Kidney ◽  
Renal Epithelial Cells ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cyst Growth

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is caused by germline mutations of PKD1 or PKD2 on one allele and a somatic mutation inactivating the remaining normal allele. However, if and how null ADPKD gene renal epithelial cells affect the biology and function of neighboring cells, including heterozygous renal epithelial cells, fibroblasts and macrophages during cyst initiation and expansion remains unknown. Here we address this question with a “cystic extracellular vesicles/exosomes theory”. We show that cystic cell derived extracellular vesicles and urinary exosomes derived from ADPKD patients promote cyst growth in Pkd1 mutant kidneys and in 3D cultures. This is achieved by: 1) downregulation of Pkd1 gene expression and upregulation of specific miRNAs, resulting in the activation of PKD associated signaling pathways in recipient renal epithelial cells and tissues; 2) the activation of fibroblasts; and 3) the induction of cytokine expression and the recruitment of macrophages to increase renal inflammation in cystic kidneys. Inhibition of exosome biogenesis/release with GW4869 significantly delays cyst growth in aggressive and milder ADPKD mouse models, suggesting that targeting exosome secretion has therapeutic potential for ADPKD.

scholarly journals Nanobodies: new avenue to treat kidney disease

2021 ◽  
Author(s):  
Nicola Wanner ◽  
Thomas Eden ◽  
Nastassia Liaukouskaya ◽  
Friedrich Koch-Nolte
Keyword(s):  
Kidney Disease ◽  
Single Domain ◽  
Therapeutic Options ◽  
Renal Diseases ◽  
Single Domain Antibodies ◽  
Potential Use ◽  
Disease Specific

AbstractCurrent therapeutic options for renal diseases are limited, and the search for disease-specific treatments is ongoing. Nanobodies, single-domain antibodies with many advantages over conventional antibodies, provide flexible, easy-to-format biologicals with many possible applications. Here, we discuss the potential use of nanobodies for renal diseases.

scholarly journals Extracellular vesicles as immune mediators in response to kidney injury

2018 ◽  
Vol 314 (1) ◽  
pp. F9-F21 ◽  
Author(s):  
Eva Feigerlová ◽  
Shyue-Fang Battaglia-Hsu ◽  
Thierry Hauet ◽  
Jean-Louis Guéant
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Bioactive Molecules ◽  
Renal Diseases ◽  
Cytokine Signaling ◽  
Renal Tubular ◽  
Tissue Recovery

Important progress has been made on cytokine signaling in response to kidney injury in the past decade, especially cytokine signaling mediated by extracellular vesicles (EVs). For example, EVs released by injured renal tubular epithelial cells (TECs) can regulate intercellular communications and influence tissue recovery via both regulating the expression and transferring cytokines, growth factors, as well as other bioactive molecules at the site of injury. The effects of EVs on kidney tissue seem to vary depending on the sources of EVs; however, the literature data are often inconsistent. For example, in rodents EVs derived from mesenchymal stem cells (MSC-EVs) and endothelial progenitor cells (EPC-EVs) can have both beneficial and harmful effects on injured renal tissue. Caution is thus needed in the interpretation of these data as contradictory findings on EVs may not only be related to the origin of EVs, they can also be caused by the different methods used for EV isolation and the physiological and pathological states of the tissues/cells under which they were obtained. Here, we review and discuss our current understanding related to the immunomodulatory function of EVs in renal tubular repair in the hope of encouraging further investigations on mechanisms related to their antiinflammatory and reparative role to better define the therapeutic potential of EVs in renal diseases.

scholarly journals Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy

2021 ◽  
Vol 10 ◽  
Author(s):  
Yifan Ma ◽  
Shiyan Dong ◽  
Xuefeng Li ◽  
Betty Y. S. Kim ◽  
Zhaogang Yang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Extracellular Vesicles ◽  
Drug Delivery Systems ◽  
Current Knowledge ◽  
Drug Loading ◽  
Cell Communication ◽  
Cancer Therapies ◽  
Therapeutic Function ◽  
Cancer Studies ◽  
Potential Use

Extracellular vesicles (EVs) are cell-derived membrane particles that represent an endogenous mechanism for cell-to-cell communication. Since discovering that EVs have multiple advantages over currently available delivery platforms, such as their ability to overcome natural barriers, intrinsic cell targeting properties, and circulation stability, the potential use of EVs as therapeutic nanoplatforms for cancer studies has attracted considerable interest. To fully elucidate EVs’ therapeutic function for treating cancer, all current knowledge about cellular uptake and trafficking of EVs will be initially reviewed. In order to further improve EVs as anticancer therapeutics, engineering strategies for cancer therapy have been widely explored in the last decade, along with other cancer therapies. However, therapeutic applications of EVs as drug delivery systems have been limited because of immunological concerns, lack of methods to scale EV production, and efficient drug loading. We will review and discuss recent progress and remaining challenges in developing EVs as a delivery nanoplatform for cancer therapy.

scholarly journals Extracellular Vesicles: An Emerging Mechanism Governing the Secretion and Biological Roles of Tenascin-C

2021 ◽  
Vol 12 ◽  
Author(s):  
Lucas Albacete-Albacete ◽  
Miguel Sánchez-Álvarez ◽  
Miguel Angel del Pozo
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Cell Types ◽  
Target Cells ◽  
Tenascin C ◽  
Signalling Molecules ◽  
Inflammatory Processes ◽  
Bona Fide ◽  
Cellular Components

ECM composition and architecture are tightly regulated for tissue homeostasis. Different disorders have been associated to alterations in the levels of proteins such as collagens, fibronectin (FN) or tenascin-C (TnC). TnC emerges as a key regulator of multiple inflammatory processes, both during physiological tissue repair as well as pathological conditions ranging from tumor progression to cardiovascular disease. Importantly, our current understanding as to how TnC and other non-collagen ECM components are secreted has remained elusive. Extracellular vesicles (EVs) are small membrane-bound particles released to the extracellular space by most cell types, playing a key role in cell-cell communication. A broad range of cellular components can be transported by EVs (e.g. nucleic acids, lipids, signalling molecules and proteins). These cargoes can be transferred to target cells, potentially modulating their function. Recently, several extracellular matrix (ECM) proteins have been characterized as bona fide EV cargoes, exosomal secretion being particularly critical for TnC. EV-dependent ECM secretion might underpin diseases where ECM integrity is altered, establishing novel concepts in the field such as ECM nucleation over long distances, and highlighting novel opportunities for diagnostics and therapeutic intervention. Here, we review recent findings and standing questions on the molecular mechanisms governing EV–dependent ECM secretion and its potential relevance for disease, with a focus on TnC.

scholarly journals The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Mingxuan Chi ◽  
Kuai Ma ◽  
Jing Wang ◽  
Zhaolun Ding ◽  
Yunlong Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Renal Diseases

The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy.

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