Exosomes and extracellular vesicles: the path forward

2018 ◽  
Vol 62 (2) ◽  
pp. 119-124 ◽  
Author(s):  
Philip D. Stahl ◽  
Graça Raposo
Keyword(s):  
Extracellular Vesicles ◽  
Cell Biology ◽  
Biological Fluids ◽  
Therapeutic Agents ◽  
Tissue Homeostasis ◽  
The Past ◽  
And Function ◽  
Intercellular Communications ◽  
Biomedical Community

Over the course of the past several decades, the concept that extracellular vesicles, exosomes and microvesicles, operate as cellular “housekeepers” and as agents for communication between and among cells and tissues, has emerged into one of the most promising yet vexing problems facing the biomedical community. Already, extracellular vesicles from biological fluids are being used for diagnostic purposes and hopes abound for their use as therapeutic agents. However, the most basic mechanistic questions surrounding their biogenesis and function in cellular and tissue homeostasis remain largely unexplored. In this issue of Essays in Biochemistry, the rise of a new intercellular communications pathway is considered from many perspectives—cell biology, physiology, and pathophysiology.

Biological Phase Separation and Biomolecular Condensates in Plants

2021 ◽  
Vol 72 (1) ◽  
Author(s):  
Ryan J. Emenecker ◽  
Alex S. Holehouse ◽  
Lucia C. Strader
Keyword(s):  
Phase Separation ◽  
Cell Biology ◽  
Condensed Matter ◽  
Annual Review ◽  
Publication Date ◽  
Nuclear Speckles ◽  
The Past ◽  
Shared Property ◽  
And Function ◽  
Physical Principles

A surge in research focused on understanding the physical principles governing the formation, properties, and function of membraneless compartments has occurred over the past decade. Compartments such as the nucleolus, stress granules, and nuclear speckles have been designated as biomolecular condensates to describe their shared property of spatially concentrating biomolecules. Although this research has historically been carried out in animal and fungal systems, recent work has begun to explore whether these same principles are relevant in plants. Effectively understanding and studying biomolecular condensates require interdisciplinary expertise that spans cell biology, biochemistry, and condensed matter physics and biophysics. As such, some involved concepts may be unfamiliar to any given individual. This review focuses on introducing concepts essential to the study of biomolecular condensates and phase separation for biologists seeking to carry out research in this area and further examines aspects of biomolecular condensates that are relevant to plant systems. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Extracellular Vesicles as Biological Shuttles for Targeted Therapies

2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Special Focus ◽  
Pathological Conditions ◽  
Critical Issues ◽  
Membrane Bound ◽  
And Function ◽  
Potential Use

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.

scholarly journals Advances in therapeutic applications of extracellular vesicles

2019 ◽  
Vol 11 (492) ◽  
pp. eaav8521 ◽  
Author(s):  
Oscar P. B. Wiklander ◽  
Meadhbh Á. Brennan ◽  
Jan Lötvall ◽  
Xandra O. Breakefield ◽  
Samir EL Andaloussi
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Immune Modulation ◽  
Lipid Membrane ◽  
Therapeutic Agents ◽  
Bioactive Components ◽  
Pathological Conditions ◽  
Delivery Vehicles ◽  
And Function

Extracellular vesicles (EVs) are nanometer-sized, lipid membrane–enclosed vesicles secreted by most, if not all, cells and contain lipids, proteins, and various nucleic acid species of the source cell. EVs act as important mediators of intercellular communication that influence both physiological and pathological conditions. Given their ability to transfer bioactive components and surmount biological barriers, EVs are increasingly being explored as potential therapeutic agents. EVs can potentiate tissue regeneration, participate in immune modulation, and function as potential alternatives to stem cell therapy, and bioengineered EVs can act as delivery vehicles for therapeutic agents. Here, we cover recent approaches and advances of EV-based therapies.

scholarly journals Skeletal muscle releases extracellular vesicles with distinct protein and miRNA signatures that accumulate and function within the muscle microenvironment

2021 ◽  
Author(s):  
Sho Watanabe ◽  
Yuri Sudo ◽  
Satoshi Kimura ◽  
Kenji Tomita ◽  
Makoto Noguchi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
The Body ◽  
C2c12 Cells ◽  
Ips Cell ◽  
Potential Marker ◽  
And Function ◽  
Intercellular Communications

Extracellular vesicles (EVs) contain various regulatory molecules and mediate intercellular communications. Although EVs are secreted from various cell types, including skeletal muscle cells, and present in the blood, their identity is poorly characterized in vivo, limiting the identification of their origin in the blood. Since the skeletal muscle is the largest organ in the body, it could substantially contribute to circulating EVs as their source. However, due to the lack of defined markers that distinguish SkM-EVs from others, whether the skeletal muscle releases EVs in vivo and how much the skeletal muscle-derived EVs (SkM-EVs) account for plasma EVs remain poorly understood. In this work, we perform quantitative proteomic analyses on EVs released from C2C12 cells and human iPS cell-derived myocytes and identify potential marker proteins that mark SkM-EVs. These markers we identified apply to in vivo tracking of SkM-EVs. The results show that skeletal muscle makes only a subtle contribution to plasma EVs as their source in both control and exercise conditions in mice. On the other hand, we demonstrate that SkM-EVs are concentrated in the skeletal muscle interstitium. Furthermore, we show that interstitium EVs are highly enriched with the muscle-specific miRNAs and repress the expression of the paired box transcription factor Pax7, a master regulator for myogenesis. Taken together, our findings reveal that the skeletal muscle releases exosome-like small EVs with distinct protein and miRNA profiles in vivo and that SkM-EVs mainly play a role within the muscle microenvironment where they accumulate.

scholarly journals Microvilli-derived Extracellular Vesicles Govern Morphogenesis in Drosophila wing epithelium

2020 ◽  
Author(s):  
Ilse Hurbain ◽  
Anne-Sophie Macé ◽  
Maryse Romao ◽  
Lucie Sengmanivong ◽  
Laurent Ruel ◽  
...  
Keyword(s):  
Long Range ◽  
Extracellular Vesicles ◽  
Cell Biology ◽  
Extracellular Vesicle ◽  
Wing Disc ◽  
Cellular Mechanisms ◽  
Long Distance ◽  
Drosophila Wing ◽  
And Function

ABSTRACTThe regulation and coordination of developmental processes involves the secretion of morphogens and membrane carriers, including extracellular vesicles, which facilitate their transport over long distance. The long-range activity of the Hedgehog morphogen is conveyed by extracellular vesicles. However, the site and the molecular basis of their biogenesis remains unknown. By combining fluorescence and electron microscopy combined with genetics and cell biology approaches, we investigated the origin and the cellular mechanisms underlying extracellular vesicle biogenesis, and their contribution to Drosophila wing disc development, exploiting Hedgehog as a long-range morphogen. We show that microvilli of Drosophila wing disc epithelium are the site of generation of small extracellular vesicles that transport Hedgehog across the tissue. This process requires the Prominin-like protein, whose activity, together with interacting cytoskeleton components and lipids, is critical for maintaining microvilli integrity and function in secretion. Our results provide the first evidence that microvilli-derived extracellular vesicles contribute to Hedgehog long-range signaling activity highlighting their physiological significance in tissue development in vivo.

scholarly journals Extracellular vesicles in the host-helminth communication: biomedical applications

2021 ◽  
Vol 87 (87(03)) ◽  
pp. 351-360
Author(s):  
Antonio Marcilla Díaz
Keyword(s):  
Extracellular Vesicles ◽  
Biomedical Applications ◽  
Lipid Membrane ◽  
Biological Fluids ◽  
Different Types ◽  
Health And Disease ◽  
Secretion Of Mediators ◽  
New Treatments ◽  
Intercellular Communications ◽  
Biomedical Interest

Extracellular vesicles participate in intercellular communications, altogether with classic mechanisms like direct contact between cells and the secretion of mediators. They have attracted considerable interest since their discovery in reticulocytes in 1983. The term includes different types of vesicles that vary in size and origin, with exosomes, microvesicles and apoptotic bodies as the major ones. These structures are sorrounded by a lipid membrane, where various types of receptors are located, and can carry different cargo molecules, including sugars, proteins, nucleic acids and metabolites. They have been described in all kingdoms in nature (participating in both intercellular and inter-specific communications), in all types of biological fluids (as part of liquid biopsy). In fact, their presence in samples from both physiological and pathological processes has suggested them as excellent biomarkers. Their role in health and disease is being widely investigated. In this context, the study of extracellular vesicles produced by parasites, and specifically by helminths, constitutes a growing field of research, with great biomedical interest, mainly in the control of infections caused by them. In fact, these vesicles can be used to generate rapid and specific diagnosis systems, to produce new tools for vaccination, and to identify targets for new treatments. The ability of extracellular vesicles to modulate the immune response also opens new possibilities for their use against autoimmune diseases.

scholarly journals Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers

2019 ◽  
Vol 20 (13) ◽  
pp. 3272 ◽  
Author(s):  
Suet Yen Chong ◽  
Choon Keong Lee ◽  
Chenyuan Huang ◽  
Yi Hsuan Ou ◽  
Christopher J. Charles ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cardiovascular Diseases ◽  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Intrinsic Activity ◽  
Diagnostic Tools ◽  
Alternative Source ◽  
Technological Advantage

Cardiovascular diseases (CVD) represent the leading cause of morbidity and mortality globally. The emerging role of extracellular vesicles (EVs) in intercellular communication has stimulated renewed interest in exploring the potential application of EVs as tools for diagnosis, prognosis, and therapy in CVD. The ubiquitous nature of EVs in biological fluids presents a technological advantage compared to current diagnostic tools by virtue of their notable stability. EV contents, such as proteins and microRNAs, represent specific signatures of cellular activation or injury. This feature positions EVs as an alternative source of biomarkers. Furthermore, their intrinsic activity and immunomodulatory properties offer EVs unique opportunities to act as therapeutic agents per se or to serve as drug delivery carriers by acting as miniaturized vehicles incorporating bioactive molecules. In this article, we aim to review the recent advances and applications of EV-based biomarkers and therapeutics. In addition, the potential of EVs as a drug delivery and theranostic platform for CVD will also be discussed.

scholarly journals Advances in Neurotrophic Factor and Cell-Based Therapies for Parkinson's Disease: A Mini-Review

Gerontology ◽  
2015 ◽  
Vol 62 (3) ◽  
pp. 371-380 ◽  
Author(s):  
Michael D. Staudt ◽  
Andrea R. Di Sebastiano ◽  
Hu Xu ◽  
Mandar Jog ◽  
Susanne Schmid ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Therapeutic Agents ◽  
The Past ◽  
Cell Based Therapy ◽  
Recent Developments ◽  
Biological Sources ◽  
And Function ◽  
Disease Modifying Treatment ◽  
Host Brain

Parkinson's disease (PD) affects an estimated 7-10 million people worldwide and remains without definitive or disease-modifying treatment. There have been many recent developments in cell-based therapy (CBT) to replace lost circuitry and provide chronic biological sources of therapeutic agents to the PD-affected brain. Early neural transplantation studies underscored the challenges of immune compatibility, graft integration and the need for renewable, autologous graft sources. Neurotrophic factors (NTFs) offer a potential class of cytoprotective pharmacotherapeutics that may complement dopamine (DA) replacement and CBT strategies in PD. Chronic NTF delivery may be an integral goal of CBT, with grafts consisting of autologous drug-producing (e.g., DA, NTF) cells that are capable of integration and function in the host brain. In this mini-review, we outline the past experience and recent advances in NTF technology and CBT as promising and integrated approaches for the treatment of PD.

scholarly journals Stiffness Sensing by Cells

2020 ◽  
Vol 100 (2) ◽  
pp. 695-724 ◽  
Author(s):  
Paul A. Janmey ◽  
Daniel A. Fletcher ◽  
Cynthia A. Reinhart-King
Keyword(s):  
Cell Biology ◽  
Cell Structure ◽  
Structure And Function ◽  
Substrate Stiffness ◽  
Common Features ◽  
The Past ◽  
Simple Rules ◽  
Physical Stimuli ◽  
Disease Initiation ◽  
And Function

Physical stimuli are essential for the function of eukaryotic cells, and changes in physical signals are important elements in normal tissue development as well as in disease initiation and progression. The complexity of physical stimuli and the cellular signals they initiate are as complex as those triggered by chemical signals. One of the most important, and the focus of this review, is the effect of substrate mechanical properties on cell structure and function. The past decade has produced a nearly exponentially increasing number of mechanobiological studies to define how substrate stiffness alters cell biology using both purified systems and intact tissues. Here we attempt to identify common features of mechanosensing in different systems while also highlighting the numerous informative exceptions to what in early studies appeared to be simple rules by which cells respond to mechanical stresses.

scholarly journals Macrophages: an indispensable piece of ovarian health†

2020 ◽  
Author(s):  
Zijing Zhang ◽  
Lu Huang ◽  
Lynae Brayboy
Keyword(s):  
Immune Cells ◽  
Innate Immune System ◽  
Ovarian Tissue ◽  
Tissue Homeostasis ◽  
Innate Immune ◽  
The Past ◽  
Heterogeneous Tissue ◽  
And Function ◽  
Key Questions

Abstract Macrophages are the most abundant immune cells in the ovary. In addition to their roles in the innate immune system, these heterogeneous tissue-resident cells are responsive to tissue-derived signals, adapt to their local tissue environment, and specialize in unique functions to maintain tissue homeostasis. Research in the past decades has established a strong link between macrophages and various aspects of ovarian physiology, indicating a pivotal role of macrophages in ovarian health. However, unlike other intensively studied organs, the knowledge of ovarian macrophages dates back to the time when the heterogeneity of ontogeny, phenotype and function of macrophages was not fully understood. In this review, we discuss the evolving understanding of the biology of ovarian tissue-resident macrophages, highlight their regulatory roles in normal ovarian functions, review the association between certain ovarian pathologies and disturbed macrophage homeostasis, and finally, discuss the technologies that are essential for addressing key questions in the field.

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