scholarly journals Extracellular Vesicles as Intercellular Communication Vehicles in Regenerative Medicine

2021 ◽  
Author(s):  
Gaspar Bogdan Severus ◽  
Ionescu Ruxandra Florentina ◽  
Enache Robert Mihai ◽  
Dobrică Elena Codruța ◽  
Crețoiu Sanda Maria ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Potential Application ◽  
Therapeutic Potential ◽  
Disease Diagnosis ◽  
Circulating Biomarkers ◽  
Early Disease ◽  
Slowing Down

Extracellular vesicles (EVs) represent cell-specific carriers of bioactive cargos that can be of importance in either physiological or pathological processes. Frequently, EVs are seen as intercellular communication vehicles, but it has become more and more evident that their usefulness can vary from circulating biomarkers for an early disease diagnosis to future therapeutic carriers for slowing down the evolution of different afflictions and their ability to restore damaged tissue/organs. Here, we summarize the latest progress of EVs classification, biogenesis, and characteristics. We also briefly discuss their therapeutic potential, with emphasis on their potential application in regenerative medicine.

Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chronic Liver Injury ◽  
Mediated Effects ◽  
Therapeutic Benefits

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.

scholarly journals Advances in Technologies for Purification and Enrichment of Extracellular Vesicles

2019 ◽  
Vol 24 (5) ◽  
pp. 477-488 ◽  
Author(s):  
Pan Zhang ◽  
Joo Chuan Yeo ◽  
Chwee Teck Lim
Keyword(s):  
Lipid Bilayer ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Disease Diagnosis ◽  
Future Developments ◽  
Enrichment Technology

Extracellular vesicles (EVs) are lipid bilayer-bound vesicles secreted by cells. Subtypes of EVs such as microvesicles and exosomes are further categorized mainly by their different biogenesis mechanisms. EVs have been revealed to play an important role in disease diagnosis and intercellular communication. Despite the wide interest in EVs, the technologies for the purification and enrichment of EVs are still in their infancy. The isolation of EVs, especially exosomes, is inherently challenging due to their small size and heterogeneity. In this review, we mainly introduce the advances of techniques in isolating microvesicles and exosomes according to their approaches. Also, we discuss the limitations of currently reported technologies in terms of their specificity and efficiency, and provide our thoughts about future developments of EV purification and enrichment technology.

scholarly journals The Emerging Role of Extracellular Vesicles in the Glioma Microenvironment: Biogenesis and Clinical Relevance

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1964
Author(s):  
Anjali Balakrishnan ◽  
Sabrina Roy ◽  
Taylor Fleming ◽  
Hon S. Leong ◽  
Carol Schuurmans
Keyword(s):  
Tumor Progression ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Cell Types ◽  
Disease Diagnosis ◽  
Neural Cells ◽  
Cell Of Origin ◽  
Cell Type Specificity ◽  
Normal Cells ◽  
Mediate Cell

Gliomas are a diverse group of brain tumors comprised of malignant cells (‘tumor’ cells) and non-malignant ‘normal’ cells, including neural (neurons, glia), inflammatory (microglia, macrophage) and vascular cells. Tumor heterogeneity arises in part because, within the glioma mass, both ‘tumor’ and ‘normal’ cells secrete factors that form a unique microenvironment to influence tumor progression. Extracellular vesicles (EVs) are critical mediators of intercellular communication between immediate cellular neighbors and distantly located cells in healthy tissues/organs and in tumors, including gliomas. EVs mediate cell–cell signaling as carriers of nucleic acid, lipid and protein cargo, and their content is unique to cell types and physiological states. EVs secreted by non-malignant neural cells have important physiological roles in the healthy brain, which can be altered or co-opted to promote tumor progression and metastasis, acting in combination with glioma-secreted EVs. The cell-type specificity of EV content means that ‘vesiculome’ data can potentially be used to trace the cell of origin. EVs may also serve as biomarkers to be exploited for disease diagnosis and to assess therapeutic progress. In this review, we discuss how EVs mediate intercellular communication in glioma, and their potential role as biomarkers and readouts of a therapeutic response.

scholarly journals Therapeutic Potential of Mesenchymal Stem Cells (MSCs) and MSC-Derived Extracellular Vesicles for the Treatment of Spinal Cord Injury

2021 ◽  
Vol 22 (24) ◽  
pp. 13672
Author(s):  
Gang-Un Kim ◽  
Soo-Eun Sung ◽  
Kyung-Ku Kang ◽  
Joo-Hee Choi ◽  
Sijoon Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Structural Changes ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Permanent Disability ◽  
Cord Injury ◽  
Anti Inflammatory

Spinal cord injury (SCI) is a life-threatening condition that leads to permanent disability with partial or complete loss of motor, sensory, and autonomic functions. SCI is usually caused by initial mechanical insult, followed by a cascade of several neuroinflammation and structural changes. For ameliorating the neuroinflammatory cascades, MSC has been regarded as a therapeutic agent. The animal SCI research has demonstrated that MSC can be a valuable therapeutic agent with several growth factors and cytokines that may induce anti-inflammatory and regenerative effects. However, the therapeutic efficacy of MSCs in animal SCI models is inconsistent, and the optimal method of MSCs remains debatable. Moreover, there are several limitations to developing these therapeutic agents for humans. Therefore, identifying novel agents for regenerative medicine is necessary. Extracellular vesicles are a novel source for regenerative medicine; they possess nucleic acids, functional proteins, and bioactive lipids and perform various functions, including damaged tissue repair, immune response regulation, and reduction of inflammation. MSC-derived exosomes have advantages over MSCs, including small dimensions, low immunogenicity, and no need for additional procedures for culture expansion or delivery. Certain studies have demonstrated that MSC-derived extracellular vesicles (EVs), including exosomes, exhibit outstanding chondroprotective and anti-inflammatory effects. Therefore, we reviewed the principles and patho-mechanisms and summarized the research outcomes of MSCs and MSC-derived EVs for SCI, reported to date.

scholarly journals Small extracellular vesicles from menstrual blood-derived mesenchymal stem cells (MenSCs) as a novel therapeutic impetus in regenerative medicine

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lijun Chen ◽  
Jingjing Qu ◽  
Quanhui Mei ◽  
Xin Chen ◽  
Yangxin Fang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Clinical Medicine ◽  
Therapeutic Potential ◽  
Menstrual Blood ◽  
Therapeutic Effects ◽  
Basic Characteristics ◽  
Novel Therapeutic

AbstractMenstrual blood-derived mesenchymal stem cells (MenSCs) have great potential in regenerative medicine. MenSC has received increasing attention owing to its impressive therapeutic effects in both preclinical and clinical trials. However, the study of MenSC-derived small extracellular vesicles (EVs) is still in its initial stages, in contrast to some common MSC sources (e.g., bone marrow, umbilical cord, and adipose tissue). We describe the basic characteristics and biological functions of MenSC-derived small EVs. We also demonstrate the therapeutic potential of small EVs in fulminant hepatic failure, myocardial infarction, pulmonary fibrosis, prostate cancer, cutaneous wound, type-1 diabetes mellitus, aged fertility, and potential diseases. Subsequently, novel hotspots with respect to MenSC EV-based therapy are proposed to overcome current challenges. While complexities regarding the therapeutic potential of MenSC EVs continue to be unraveled, advances are rapidly emerging in both basic science and clinical medicine. MenSC EV-based treatment has great potential for treating a series of diseases as a novel therapeutic strategy in regenerative medicine.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Potential

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ashley G. Zhao ◽  
Kiran Shah ◽  
Brett Cromer ◽  
Huseyin Sumer
Keyword(s):  
Tissue Engineering ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Multipotent Cells ◽  
Membrane Bound

Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles, which act as shuttles, delivering a range of biomolecules to diverse target cells. They play an important role in maintenance of biophysiological homeostasis and cellular, physiological, and pathological processes. EVs have significant diagnostic and therapeutic potentials and have been studied both in vitro and in vivo in many fields. Mesenchymal stem cells (MSCs) are multipotent cells with many therapeutic applications and have also gained much attention as prolific producers of EVs. MSC-derived EVs are being explored as a therapeutic alternative to MSCs since they may have similar therapeutic effects but are cell-free. They have applications in regenerative medicine and tissue engineering and, most importantly, confer several advantages over cells such as lower immunogenicity, capacity to cross biological barriers, and less safety concerns. In this review, we introduce the biogenesis of EVs, including exosomes and microvesicles. We then turn more specifically to investigations of MSC-derived EVs. We highlight the great therapeutic potential of MSC-derived EVs and applications in regenerative medicine and tissue engineering.

scholarly journals Extracellular Vesicle Quantification and Characterization: Common Methods and Emerging Approaches

2019 ◽  
Vol 6 (1) ◽  
pp. 7 ◽  
Author(s):  
Thomas Hartjes ◽  
Serhii Mytnyk ◽  
Guido Jenster ◽  
Volkert van Steijn ◽  
Martin van Royen
Keyword(s):  
Physical Properties ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Therapeutic Potential ◽  
Membrane Vesicles ◽  
Extracellular Vesicle ◽  
Medical Applications ◽  
Accurate Assessment ◽  
Further Development

Extracellular vesicles (EVs) are a family of small membrane vesicles that carry information about cells by which they are secreted. Growing interest in the role of EVs in intercellular communication, but also in using their diagnostic, prognostic and therapeutic potential in (bio) medical applications, demands for accurate assessment of their biochemical and physical properties. In this review, we provide an overview of available technologies for EV analysis by describing their working principles, assessing their utility in EV research and summarising their potential and limitations. To emphasise the innovations in EV analysis, we also highlight the unique possibilities of emerging technologies with high potential for further development.

Separation of Extracellular Vesicles by DNA-Directed Immunocapturing Followed by Enzymatic Release

2020 ◽  
Author(s):  
Dario Brambilla ◽  
Laura Sola ◽  
Elisa Chiodi ◽  
Natasa Zarovni ◽  
Diogo Fortunato ◽  
...  
Keyword(s):  
Cell Culture ◽  
Extracellular Vesicles ◽  
Culture Media ◽  
Biological Fluids ◽  
Imaging Techniques ◽  
Cell Communication ◽  
Disease Diagnosis ◽  
Cell Culture Supernatant ◽  
Transmission Electron ◽  
Downstream Analysis

Extracellular vesicles (EVs) have attracted great interest among researchers due to their role in cell-cell communication, disease diagnosis, and drug delivery. In spite of their potential in the medical field, there is no consensus on the best method for separating microvesicles from cell culture supernatant and complex biological fluids. Obtaining a good recovery yield and preserving physical characteristics is critical for the diagnostic and therapeutic use of EVs. The separation is made complex by the fact that blood and cell culture media, contain a large number of nanoparticles in the same size range. Methods that exploit immunoaffinity capture provide high purity samples and overcome the issues of currently used separation methods. However, the release of captured nanovesicles requires harsh conditions that hinder their use in certain types of downstream analysis. Herein, a novel capture and release approach for small extracellular vesicles (sEVs), based on DNAdirected immobilization of antiCD63 antibody is presented. The flexible DNAlinker increases the capture efficiency and allows releasing of EVs by exploiting the endonucleasic activity of DNAse I. This separation protocol works under mild conditions, enabling the release of intact vesicles that can be successfully analyzed by imaging techniques. In this article sEVs recovered from plasma were characterized by established techniques for EVs analysis including nanoparticle tracking and transmission electron microscopy.<br>

Exosome: An Emerging Source of Biomarkers for Human Diseases

2019 ◽  
Vol 19 (6) ◽  
pp. 387-394 ◽  
Author(s):  
Li Xu ◽  
Long-Fei Wu ◽  
Fei-Yan Deng
Keyword(s):  
Breast Milk ◽  
Intercellular Communication ◽  
Translational Medicine ◽  
Disease Diagnosis ◽  
Human Diseases ◽  
Isolation And Identification ◽  
Biomarker Identification ◽  
Biological Features ◽  
Diagnosis And Prognosis ◽  
Novel Biomarkers

Exosomes are 30-120nm long endocytic membrane-derived vesicles, which are secreted by various types of cells and stably present in body fluids, such as plasma, urine, saliva and breast milk. Exosomes participate in intercellular communication. Recently accumulative studies have suggested that exosomes may serve as novel biomarkers for disease diagnosis and prognosis. Herein, we reviewed the biological features of exosomes, technologies for exosome isolation and identification, as well as progress in exosomal biomarker identification, highlighting the relevance of exosome to human diseases and significance and great potential in translational medicine.

scholarly journals Single Step In Situ Detection of Surface Protein and MicroRNA in Clustered Extracellular Vesicles Using Flow Cytometry

2021 ◽  
Vol 10 (2) ◽  
pp. 319
Author(s):  
Hee Cheol Yang ◽  
Won Jong Rhee
Keyword(s):  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Molecular Beacon ◽  
Disease Diagnosis ◽  
Single Step ◽  
Flow Cytometer ◽  
Surface Proteins ◽  
Biomarker Detection ◽  
In Situ Detection

Because cancers are heterogeneous, it is evident that multiplexed detection is required to achieve disease diagnosis with high accuracy and specificity. Extracellular vesicles (EVs) have been a subject of great interest as sources of novel biomarkers for cancer liquid biopsy. However, EVs are nano-sized particles that are difficult to handle; thus, it is necessary to develop a method that enables efficient and straightforward EV biomarker detection. In the present study, we developed a method for single step in situ detection of EV surface proteins and inner miRNAs simultaneously using a flow cytometer. CD63 antibody and molecular beacon-21 were investigated for multiplexed biomarker detection in normal and cancer EVs. A phospholipid-polymer-phospholipid conjugate was introduced to induce clustering of the EVs analyzed using nanoparticle tracking analysis, which enhanced the detection signals. As a result, the method could detect and distinguish cancer cell-derived EVs using a flow cytometer. Thus, single step in situ detection of multiple EV biomarkers using a flow cytometer can be applied as a simple, labor- and time-saving, non-invasive liquid biopsy for the diagnosis of various diseases, including cancer.

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