scholarly journals Exosomes in disease and regeneration: biological functions, diagnostics, and beneficial effects

2020 ◽  
Vol 319 (6) ◽  
pp. H1162-H1180
Author(s):  
Yun Lin ◽  
Johnathon D. Anderson ◽  
Lily M. A. Rahnama ◽  
Shenwen V. Gu ◽  
Anne A. Knowlton

Exosomes are a subtype of extracellular vesicles. They range from 30 to 150 nm in diameter and originate from intraluminal vesicles. Exosomes were first identified as the mechanism for releasing unnecessary molecules from reticulocytes as they matured to red blood cells. Since then, exosomes have been shown to be secreted by a broad spectrum of cells and play an important role in the cardiovascular system. Different stimuli are associated with increased exosome release and result in different exosome content. The release of harmful DNA and other molecules via exosomes has been proposed as a mechanism to maintain cellular homeostasis. Because exosomes contain parent cell-specific proteins on the membrane and in the cargo that is delivered to recipient cells, exosomes are potential diagnostic biomarkers of various types of diseases, including cardiovascular disease. As exosomes are readily taken up by other cells, stem cell-derived exosomes have been recognized as a potential cell-free regenerative therapy to repair not only the injured heart but other tissues as well. The objective of this review is to provide an overview of the biological functions of exosomes in heart disease and tissue regeneration. Therefore, state-of-the-art methods for exosome isolation and characterization, as well as approaches to assess exosome functional properties, are reviewed. Investigation of exosomes provides a new approach to the study of disease and biological processes. Exosomes provide a potential “liquid biopsy,” as they are present in most, if not all, biological fluids that are released by a wide range of cell types.

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Robert G. Wallace ◽  
Laura C. Twomey ◽  
Marc-Antoine Custaud ◽  
Niall Moyna ◽  
Philip M. Cummins ◽  
...  

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers of inflammation are not sufficiently robust in their specificity, then perhaps alternative means of detection may provide more information. Epigenetic drift (epigenetic modifications as they occur as a direct function with age), and its ancillary elements, including platelets, secreted microvesicles (MVs), and microRNA (miRNA), may hold enormous predictive potential. The majority of epigenetic drift observed in blood is independent of variations in blood cell composition, addressing concerns affecting traditional blood-based biomarker efficacy. MVs are found in plasma and other biological fluids in healthy individuals. Altered MV/miRNA profiles may also be found in individuals with various diseases. Platelets are also highly reflective of physiological and lifestyle changes, making them extremely sensitive biomarkers of human health. Platelets release increased levels of MVs in response to various stimuli and under a plethora of disease states, which demonstrate a functional effect on other cell types.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1476
Author(s):  
Marta Claudia Nocito ◽  
Arianna De Luca ◽  
Francesca Prestia ◽  
Paola Avena ◽  
Davide La Padula ◽  
...  

Curcumin, a main bioactive component of the Curcuma longa L. rhizome, is a phenolic compound that exerts a wide range of beneficial effects, acting as an antimicrobial, antioxidant, anti-inflammatory and anticancer agent. This review summarizes recent data on curcumin’s ability to interfere with the multiple cell signaling pathways involved in cell cycle regulation, apoptosis and the migration of several cancer cell types. However, although curcumin displays anticancer potential, its clinical application is limited by its low absorption, rapid metabolism and poor bioavailability. To overcome these limitations, several curcumin-based derivatives/analogues and different drug delivery approaches have been developed. Here, we also report the anticancer mechanisms and pharmacokinetic characteristics of some derivatives/analogues and the delivery systems used. These strategies, although encouraging, require additional in vivo studies to support curcumin clinical applications.


2021 ◽  
Vol 12 ◽  
Author(s):  
Patrick Santos ◽  
Fausto Almeida

Extracellular vesicles (EVs) are released by most cell types as part of an intracellular communication system in crucial processes such as inflammation, cell proliferation, and immune response. However, EVs have also been implicated in the pathogenesis of several diseases, such as cancer and numerous infectious diseases. An important feature of EVs is their ability to deliver a wide range of molecules to nearby targets or over long distances, which allows the mediation of different biological functions. This delivery mechanism can be utilized for the development of therapeutic strategies, such as vaccination. Here, we have highlighted several studies from a historical perspective, with respect to current investigations on EV-based vaccines. For example, vaccines based on exosomes derived from dendritic cells proved to be simpler in terms of management and cost-effectiveness than dendritic cell vaccines. Recent evidence suggests that EVs derived from cancer cells can be leveraged for therapeutics to induce strong anti-tumor immune responses. Moreover, EV-based vaccines have shown exciting and promising results against different types of infectious diseases. We have also summarized the results obtained from completed clinical trials conducted on the usage of exosome-based vaccines in the treatment of cancer, and more recently, coronavirus disease.


2003 ◽  
Vol 178 (2) ◽  
pp. 177-193 ◽  
Author(s):  
R Zhou ◽  
D Diehl ◽  
A Hoeflich ◽  
H Lahm ◽  
E Wolf

IGFs have multiple functions regarding cellular growth, survival and differentiation under different physiological and pathological conditions. IGF effects are modulated systemically and locally by six high-affinity IGF-binding proteins (IGFBP-1 to -6). Despite their structural similarity, each IGFBP has unique properties and exhibits specific functions. IGFBP-4, the smallest IGFBP, exists in both non-glycosylated and N-glycosylated forms in all biological fluids. It is expressed by a wide range of cell types and tIssues, and its expression is regulated by different mechanisms in a cell type-specific manner. IGFBP-4 binds IGF-I and IGF-II with similar affinities and inhibits their actions under almost all in vitro and in vivo conditions. In this review, we summarize the available data regarding the following aspects of IGFBP-4: genomic organization, protein structure-function relationship, expression and its regulation, as well as IGF-dependent and -independent actions. The biological significance of IGFBP-4 for reproductive physiology, bone formation, renal pathophysiology and cancer is discussed.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Le Zhu ◽  
Hao-Ting Sun ◽  
Shun Wang ◽  
Sheng-Lin Huang ◽  
Yan Zheng ◽  
...  

Abstract Exosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids. Moreover, exosomes carrying a wide variety of important macromolecules provide a window into altered cellular or tissue states. Their presence in biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers for cancer diagnosis, prediction, and surveillance. Due to their biocompatibility and low immunogenicity and cytotoxicity, exosomes have potential clinical applications in the development of innovative therapeutic approaches. Here, we summarize recent advances in various technologies for exosome isolation for cancer research. We outline the functions of exosomes in regulating tumor metastasis, drug resistance, and immune modulation in the context of cancer development. Finally, we discuss prospects and challenges for the clinical development of exosome-based liquid biopsies and therapeutics.


2019 ◽  
Vol 31 (9) ◽  
pp. 559-567 ◽  
Author(s):  
Tomoaki Ishihara ◽  
Mio Yoshida ◽  
Makoto Arita

AbstractOmega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, display a wide range of beneficial effects in humans and animals. Many of the biological functions of PUFAs are mediated via bioactive metabolites produced by fatty acid oxygenases such as cyclooxygenases, lipoxygenases and cytochrome P450 monooxygenases. Liquid chromatography–tandem mass spectrometry-based mediator lipidomics revealed a series of novel bioactive lipid mediators derived from omega-3 PUFAs. Here, we describe recent advances on omega-3 PUFA-derived mediators, mainly focusing on their enzymatic oxygenation pathway, and their biological functions in controlling inflammation and tissue homeostasis.


2019 ◽  
Vol 1 (1) ◽  
pp. 12-14
Author(s):  
Urwa Tanveer ◽  
Hafsa Tariq ◽  
Nargis Haider Kakar ◽  
Tariq. M. Tahir ◽  
Qurat-ul-ain Fatima ◽  
...  

Cholangiocarcinoma (CC) is one of the main crucial hepatic malignancies; hence CC is the prime cause for cancer death occurred due to bile duct cancer. A wide range of studies showed that the expression of intracellular proteins associated with the progression of tumor process might be a response of autoantibody. Unlike intracellular components, autoantibodies can appear in cancer patients long before clinical appearance of the cancer. Apparently, CC autoantibodies can appear at any point in the transformation of chronic liver disease; those autoantibodies may not apparent in erstwhile non-transformation phases, lead to a significant increase in the quantity of patients with CC positive for the presence of autoantibodies. The aim of present study was to detect the cellular proteins involved in bile duct cancer process by the use of immunoblotting technique and to predict the future biomarkers of CC. SERPA technique was applied to detect the differentially expressed proteins from nine CC patients’ sera adopting standard protocol. 2-D maps revealed a number of protein spots after gels staining. Proteins of interest were observed between pH 5 and pH8 having molecular mass range between 20 and 90 kDa. Comparative analysis of blots indicated four common immunoreactive spots in CCSW1 cell lines. These cancer specific proteins might be used for CC diagnosis at early stage.    


Author(s):  
L. M. Marshall

A human erythroleukemic cell line, metabolically blocked in a late stage of erythropoiesis, becomes capable of differentiation along the normal pathway when grown in the presence of hemin. This process is characterized by hemoglobin synthesis followed by rearrangement of the plasma membrane proteins and culminates in asymmetrical cytokinesis in the absence of nuclear division. A reticulocyte-like cell buds from the nucleus-containing parent cell after erythrocyte specific membrane proteins have been sequestered into its membrane. In this process the parent cell faces two obstacles. First, to organize its erythrocyte specific proteins at one pole of the cell for inclusion in the reticulocyte; second, to reduce or abolish membrane protein turnover since hemoglobin is virtually the only protein being synthesized at this stage. A means of achieving redistribution and cessation of turnover could involve movement of membrane proteins by a directional lipid flow. Generation of a lipid flow towards one pole and accumulation of erythrocyte-specific membrane proteins could be achieved by clathrin coated pits which are implicated in membrane endocytosis, intracellular transport and turnover. In non-differentiating cells, membrane proteins are turned over and are random in surface distribution. If, however, the erythrocyte specific proteins in differentiating cells were excluded from endocytosing coated pits, not only would their turnover cease, but they would also tend to drift towards and collect at the site of endocytosis. This hypothesis requires that different protein species are endocytosed by the coated vesicles in non-differentiating than by differentiating cells.


Author(s):  
K. Chien ◽  
R. Van de Velde ◽  
I.P. Shintaku ◽  
A.F. Sassoon

Immunoelectron microscopy of neoplastic lymphoma cells is valuable for precise localization of surface antigens and identification of cell types. We have developed a new approach in which the immunohistochemical staining can be evaluated prior to embedding for EM and desired area subsequently selected for ultrathin sectioning.A freshly prepared lymphoma cell suspension is spun onto polylysine hydrobromide- coated glass slides by cytocentrifugation and immediately fixed without air drying in polylysine paraformaldehyde (PLP) fixative. After rinsing in PBS, slides are stained by a 3-step immunoperoxidase method. Cell monolayer is then fixed in buffered 3% glutaraldehyde prior to DAB reaction. After the DAB reaction step, wet monolayers can be examined under LM for presence of brown reaction product and selected monolayers then processed by routine methods for EM and embedded with the Chien Re-embedding Mold. After the polymerization, the epoxy blocks are easily separated from the glass slides by heatingon a 100°C hot plate for 20 seconds.


2012 ◽  
Vol 9 (1) ◽  
pp. 43 ◽  
Author(s):  
Hueyling Tan

Molecular self-assembly is ubiquitous in nature and has emerged as a new approach to produce new materials in chemistry, engineering, nanotechnology, polymer science and materials. Molecular self-assembly has been attracting increasing interest from the scientific community in recent years due to its importance in understanding biology and a variety of diseases at the molecular level. In the last few years, considerable advances have been made in the use ofpeptides as building blocks to produce biological materials for wide range of applications, including fabricating novel supra-molecular structures and scaffolding for tissue repair. The study ofbiological self-assembly systems represents a significant advancement in molecular engineering and is a rapidly growing scientific and engineering field that crosses the boundaries ofexisting disciplines. Many self-assembling systems are rangefrom bi- andtri-block copolymers to DNA structures as well as simple and complex proteins andpeptides. The ultimate goal is to harness molecular self-assembly such that design andcontrol ofbottom-up processes is achieved thereby enabling exploitation of structures developed at the meso- and macro-scopic scale for the purposes oflife and non-life science applications. Such aspirations can be achievedthrough understanding thefundamental principles behind the selforganisation and self-synthesis processes exhibited by biological systems.


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