International Journal of Molecular Sciences

Editorial

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4 pages, 187 KiB

Open AccessEditorial

Extracellular Vesicles and Cell–Cell Communication: New Insights and New Therapeutic Strategies Not Only in Oncology

by Frank Gieseler and Fanny Ender

Int. J. Mol. Sci. 2020, 21(12), 4331; https://doi.org/10.3390/ijms21124331 - 18 Jun 2020

Cited by 6 | Viewed by 1967

Abstract

The discovery that tumors are not separated from systemic regulatory mechanisms of the body but are rather integrated into them, and even use these mechanisms for their own purposes, was one of the most important findings in tumor biology of the last few [...] Read more.

The discovery that tumors are not separated from systemic regulatory mechanisms of the body but are rather integrated into them, and even use these mechanisms for their own purposes, was one of the most important findings in tumor biology of the last few years [...] Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

Research

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15 pages, 6504 KiB

Open AccessArticle

Comparative Proteomic Profiling of Secreted Extracellular Vesicles from Breast Fibroadenoma and Malignant Lesions: A Pilot Study

by Katia Pane, Cristina Quintavalle, Silvia Nuzzo, Francesco Ingenito, Giuseppina Roscigno, Alessandra Affinito, Iolanda Scognamiglio, Birlipta Pattanayak, Enrico Gallo, Antonella Accardo, Guglielmo Thomas, Zoran Minic, Maxim V. Berezovski, Monica Franzese and Gerolama Condorelli

Int. J. Mol. Sci. 2022, 23(7), 3989; https://doi.org/10.3390/ijms23073989 - 3 Apr 2022

Cited by 6 | Viewed by 3904

Abstract

Extracellular vesicles (EVs) shuttle proteins, RNA, DNA, and lipids crucial for cell-to-cell communication. Recent findings have highlighted that EVs, by virtue of their cargo, may also contribute to breast cancer (BC) growth and metastatic dissemination. Indeed, EVs are gaining great interest as non-invasive [...] Read more.

Extracellular vesicles (EVs) shuttle proteins, RNA, DNA, and lipids crucial for cell-to-cell communication. Recent findings have highlighted that EVs, by virtue of their cargo, may also contribute to breast cancer (BC) growth and metastatic dissemination. Indeed, EVs are gaining great interest as non-invasive cancer biomarkers. However, little is known about the biological and physical properties of EVs from malignant BC lesions, and even less is understood about EVs from non-malignant lesions, such as breast fibroadenoma (FAD), which are clinically managed using conservative approaches. Thus, for this pilot study, we attempted to purify and explore the proteomic profiles of EVs from benign breast lesions, HER2+ BCs, triple–negative BCs (TNBCs), and continuous BC cell lines (i.e., BT-549, MCF–10A, and MDA-MB-231), combining experimental and semi-quantitative approaches. Of note, proteome-wide analyses showed 49 common proteins across EVs harvested from FAD, HER2+ BCs, TNBCs, and model BC lines. This is the first feasibility study evaluating the physicochemical composition and proteome of EVs from benign breast cells and primary and immortalized BC cells. Our preliminary results hold promise for possible implications in precision medicine for BC. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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18 pages, 4000 KiB

Open AccessArticle

Extracellular Vesicle Measurements with Nanoparticle Tracking Analysis: A Different Appreciation of Up and Down Secretion

by Clément Auger, Aude Brunel, Tiffany Darbas, Hussein Akil, Aurélie Perraud, Gaëlle Bégaud, Barbara Bessette, Niki Christou and Mireille Verdier

Int. J. Mol. Sci. 2022, 23(4), 2310; https://doi.org/10.3390/ijms23042310 - 19 Feb 2022

Cited by 14 | Viewed by 5317

Abstract

As is the case with most eucaryotic cells, cancer cells are able to secrete extracellular vesicles (EVs) as a communication means towards their environment and surrounding cells. EVs are represented by microvesicles and smaller vesicles called exosomes, which are known for their involvement [...] Read more.

As is the case with most eucaryotic cells, cancer cells are able to secrete extracellular vesicles (EVs) as a communication means towards their environment and surrounding cells. EVs are represented by microvesicles and smaller vesicles called exosomes, which are known for their involvement in cancer aggressiveness. The release of such EVs requires the intervention of trafficking-associated proteins, mostly represented by the RAB-GTPases family. In particular, RAB27A is known for its role in addressing EVs-to-be secreted towards the the plasma membrane. In this study, shRNAs targeting RAB27A were used in colorectal (CRC) and glioblastoma (GB) cell lines in order to alter EVs secretion. To study and monitor EVs secretion in cell lines’ supernatants, nanoparticle tracking analysis (NTA) was used through the NanoSight NS300 device. Since it appeared that NanoSight failed to detect the decrease in the EVs secretion, we performed another approach to drop EVs secretion (RAB27A-siRNA, indomethacin, Nexihnib20). Similar results were obtained i.e., no variation in EVs concentration. Conversely, NTA allowed us to monitor EVs up-secretion following rotenone treatment or hypoxia conditions. Therefore, our data seemed to point out the insufficiency of using only this technique for the assessment of EVs secretion decrease. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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20 pages, 5484 KiB

Open AccessArticle

MiR-519d-3p in Trophoblastic Cells: Effects, Targets and Transfer to Allogeneic Immune Cells via Extracellular Vesicles

by Wittaya Chaiwangyen, José M. Murrieta-Coxca, Rodolfo R. Favaro, Stella M. Photini, Ruby N. Gutiérrez-Samudio, Ekkehard Schleussner, Udo R. Markert and Diana M. Morales-Prieto

Int. J. Mol. Sci. 2020, 21(10), 3458; https://doi.org/10.3390/ijms21103458 - 14 May 2020

Cited by 29 | Viewed by 3716

Abstract

Members of the placenta-specific miRNA cluster C19MC, including miR-519d, are secreted by fetal trophoblast cells within extracellular vesicles (EVs). Trophoblast-derived EVs can be internalized by the autologous trophoblast and surrounding maternal immune cells, resulting in coordination of cellular responses. The study of functions [...] Read more.

Members of the placenta-specific miRNA cluster C19MC, including miR-519d, are secreted by fetal trophoblast cells within extracellular vesicles (EVs). Trophoblast-derived EVs can be internalized by the autologous trophoblast and surrounding maternal immune cells, resulting in coordination of cellular responses. The study of functions and targets of placental miRNAs in the donor and recipient cells may contribute to the understanding of the immune tolerance essential in pregnancy. Here, we report that miR-519d-3p levels correlate positively with cell proliferation and negatively with migration in trophoblastic cell lines. Inhibition of miR-519d-3p in JEG-3 cells increases caspase-3 activation and apoptosis. PDCD4 and PTEN are targeted by miR-519d-3p in a cell type-specific manner. Transfection of trophoblastic cell lines with miR-519d mimic results in secretion of EVs containing elevated levels of this miRNA (EV_miR-519d). Autologous cells enhance their proliferation and decrease their migration ability when treated with EV_miR-519d. NK92 cells incorporate EV-delivered miR-519d-3p at higher levels than Jurkat T cells. EV_miR-519d increases the proliferation of Jurkat T cells but decreases that of NK92 cells. Altogether, miR-519d-3p regulates pivotal trophoblast cell functions, can be transferred horizontally via EVs to maternal immune cells and exerts functions therein. Vesicular miRNA transfer from fetal trophoblasts to maternal immune cells may contribute to the immune tolerance in pregnancy. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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39 pages, 4277 KiB

Open AccessArticle

HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles

by Ibolya E. András, Brice B. Sewell and Michal Toborek

Int. J. Mol. Sci. 2020, 21(8), 2741; https://doi.org/10.3390/ijms21082741 - 15 Apr 2020

Cited by 11 | Viewed by 3277

Abstract

Amyloid beta (Aβ) depositions are more abundant in HIV-infected brains. The blood–brain barrier, with its backbone created by endothelial cells, is assumed to be a core player in Aβ homeostasis and may contribute to Aβ accumulation in the brain. Exposure to HIV increases [...] Read more.

Amyloid beta (Aβ) depositions are more abundant in HIV-infected brains. The blood–brain barrier, with its backbone created by endothelial cells, is assumed to be a core player in Aβ homeostasis and may contribute to Aβ accumulation in the brain. Exposure to HIV increases shedding of extracellular vesicles (EVs) from human brain endothelial cells and alters EV-Aβ levels. EVs carrying various cargo molecules, including a complex set of proteins, can profoundly affect the biology of surrounding neurovascular unit cells. In the current study, we sought to examine how exposure to HIV, alone or together with Aβ, affects the surface and total proteomic landscape of brain endothelial EVs. By using this unbiased approach, we gained an unprecedented, high-resolution insight into these changes. Our data suggest that HIV and Aβ profoundly remodel the proteome of brain endothelial EVs, altering the pathway networks and functional interactions among proteins. These events may contribute to the EV-mediated amyloid pathology in the HIV-infected brain and may be relevant to HIV-1-associated neurocognitive disorders. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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15 pages, 2090 KiB

Open AccessArticle

Extracellular Vesicles Derived from Senescent Fibroblasts Attenuate the Dermal Effect on Keratinocyte Differentiation

by Eun-Jeong Choi, In Sup Kil and Eun-Gyung Cho

Int. J. Mol. Sci. 2020, 21(3), 1022; https://doi.org/10.3390/ijms21031022 - 4 Feb 2020

Cited by 36 | Viewed by 4586

Abstract

The skin is a multilayered and primary defensive organ. Intimate intercellular communication in the skin is necessary to ensure effective surveillance. Extracellular vesicles (EVs) are being explored for their involvement in intercellular skin communication. The aim of this study was to evaluate how [...] Read more.

The skin is a multilayered and primary defensive organ. Intimate intercellular communication in the skin is necessary to ensure effective surveillance. Extracellular vesicles (EVs) are being explored for their involvement in intercellular skin communication. The aim of this study was to evaluate how human dermal fibroblasts (HDFs) accelerate EV production during senescence and the effects of senescence-associated EVs on epidermal homeostasis. Replicative senescent HDFs were assessed with senescence-associated β-galactosidase staining and the expression of senescence-related markers. Isolated EVs were characterized by dynamic light scattering and EV marker expression. EVs secreted from untreated young or senescent HDFs, or from those treated with a nSMase inhibitor, antioxidant, and lysosomal activity regulators, were determined by sandwich ELISA for CD81. Human epidermal keratinocytes were treated with young- and senescent HDF-derived EVs. Compared to young HDFs, senescent HDFs produced relatively high levels of EVs due to the increased nSMase activity, oxidative stress, and altered lysosomal activity. The nSMase inhibitor, antioxidant, and agents that recovered lysosomal activity reduced EV secretion in senescent HDFs. Relative to young HDF-derived EVs, senescent HDF-derived EVs were less supportive in keratinocyte differentiation and barrier function but increased proinflammatory cytokine IL-6 levels. Our study suggests that dermis-derived EVs may regulate epidermal homeostasis by reflecting cellular status, which provides insight as to how the dermis communicates with the epidermis and influences skin senescence. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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13 pages, 2115 KiB

Open AccessArticle

Detection and Quantification of Extracellular Vesicles via FACS: Membrane Labeling Matters!

by Fanny Ender, Piet Zamzow, Nikolas von Bubnoff and Frank Gieseler

Int. J. Mol. Sci. 2020, 21(1), 291; https://doi.org/10.3390/ijms21010291 - 31 Dec 2019

Cited by 28 | Viewed by 5615

Abstract

The field of extracellular vesicle (EV) research is challenged by the lack of standardized protocols to identify and specifically distinguish between exosomes and ectosomes, which are released via exocytosis or plasma membrane shedding, respectively. Using sequential centrifugation, we separated EV subpopulations from supernatants [...] Read more.

The field of extracellular vesicle (EV) research is challenged by the lack of standardized protocols to identify and specifically distinguish between exosomes and ectosomes, which are released via exocytosis or plasma membrane shedding, respectively. Using sequential centrifugation, we separated EV subpopulations from supernatants of COLO 357 pancreas carcinoma cells based on size and mass. After 10,000× g centrifugation, we reconstituted high-speed (hs) EVs from the pellet, directly labeled them with the membrane dye carboxyfluorescein diacetate succinimidyl ester (CFSE), and performed flow cytometry based analysis. The aim was to optimize the conditions for EV labeling and detection and hence to obtain a maximum yield of intact hsEVs. We found that, for sufficient labeling of EVs, minimal temperature variations and short incubation times correlated with EV stability. Furthermore, threshold adjustment significantly improved the sensitivity of the flow cytometer for the detection of CFSE labeled hsEVs. When cells were CFSE labeled, we observed a transition of fluorescence onto EVs that were reconstituted from the pellet but not onto those that remained in the supernatant after hs centrifugation, suggesting the indirect labeling of EVs based on the way of biogenesis as a specific method for the distinction of exosomes and ectosomes. Protocol standardization is of major importance for the use of EVs as diagnostic markers in liquid biopsies. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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20 pages, 3240 KiB

Open AccessArticle

Cardiac Extracellular Vesicles (EVs) Released in the Presence or Absence of Inflammatory Cues Support Angiogenesis in Different Manners

by Christien Madlen Beez, Maria Schneider, Marion Haag, Kathleen Pappritz, Sophie Van Linthout, Michael Sittinger and Martina Seifert

Int. J. Mol. Sci. 2019, 20(24), 6363; https://doi.org/10.3390/ijms20246363 - 17 Dec 2019

Cited by 4 | Viewed by 3889

Abstract

Cells release extracellular vesicles (EVs) to communicate in a paracrine manner with other cells, and thereby influence processes, such as angiogenesis. The conditioned medium of human cardiac-derived adherent proliferating (CardAP) cells was recently shown to enhance angiogenesis. To elucidate whether their released EVs [...] Read more.

Cells release extracellular vesicles (EVs) to communicate in a paracrine manner with other cells, and thereby influence processes, such as angiogenesis. The conditioned medium of human cardiac-derived adherent proliferating (CardAP) cells was recently shown to enhance angiogenesis. To elucidate whether their released EVs are involved, we isolated them by differential centrifugation from the conditioned medium derived either in the presence or absence of a pro-inflammatory cytokine cocktail. Murine recipient cells internalized CardAP-EVs as determined by an intracellular detection of human proteins, such as CD63, by a novel flow cytometry method for studying EV–cell interaction. Moreover, endothelial cells treated for 24 h with either unstimulated or cytokine stimulated CardAP-EVs exhibited a higher tube formation capability on Matrigel. Interestingly, unstimulated CardAP-EVs caused endothelial cells to release significantly more vascular endothelial growth factor and interleukin (IL)-6, while cytokine stimulated CardAP-EVs significantly enhanced the release of IL-6 and IL-8. By nCounter^® miRNA expression assay (NanoString Technologies) we identified microRNA 302d-3p to be enhanced in unstimulated CardAP-EVs compared to their cytokine stimulated counterparts, which was verified by quantitative polymerase chain reaction. This study demonstrates that both CardAP-EVs are pro-angiogenic by inducing different factors from endothelial cells. This would allow to select potent targets for a safe and efficient therapeutic application. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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Review

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15 pages, 565 KiB

Open AccessReview

Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease

by Erin N. Worthington and James S. Hagood

Int. J. Mol. Sci. 2020, 21(7), 2318; https://doi.org/10.3390/ijms21072318 - 27 Mar 2020

Cited by 76 | Viewed by 7834

Abstract

Multipotent mesenchymal stem cells (MSCs) possess regenerative properties and have been shown to improve outcomes and survival in acute and chronic lung diseases, but there have been some safety concerns raised related to MSC-based therapy. Subsequent studies have demonstrated that many of the [...] Read more.

Multipotent mesenchymal stem cells (MSCs) possess regenerative properties and have been shown to improve outcomes and survival in acute and chronic lung diseases, but there have been some safety concerns raised related to MSC-based therapy. Subsequent studies have demonstrated that many of the regenerative effects of MSCs can be attributed to the MSC-derived secretome, which contains soluble factors and extracellular vesicles (EVs). MSC-derived extracellular vesicles (MSC-derived EVs) replicate many of the beneficial effects of MSCs and contain a variety of bioactive factors that are transferred to recipient cells, mediating downstream signaling. MSC-derived EV therapy holds promise as a safe and effective treatment for pulmonary disease, but there remain many scientific and clinical questions that will need to be addressed before EVs are widely applied as a therapy. To date, the use of MSC-derived EVs as a treatment for lung disease has been conducted primarily in in vitro or pre-clinical animal models. In this review, we will discuss the current published research investigating the use of EVs as a potential therapeutic for acute lung injury/acute respiratory distress syndrome (ALI/ARDS), bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), asthma, and silicosis. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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29 pages, 1241 KiB

Open AccessReview

Extracellular Vesicles in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

by Tami Yap, Neha Pruthi, Christine Seers, Simone Belobrov, Michael McCullough and Antonio Celentano

Int. J. Mol. Sci. 2020, 21(4), 1197; https://doi.org/10.3390/ijms21041197 - 11 Feb 2020

Cited by 25 | Viewed by 5371

Abstract

Extracellular vesicles (EVs) are secreted from most cell types and utilized in a complex network of near and distant cell-to-cell communication. Insight into this complex nanoscopic interaction in the development, progression and treatment of oral squamous cell carcinoma (OSCC) and precancerous oral mucosal [...] Read more.

Extracellular vesicles (EVs) are secreted from most cell types and utilized in a complex network of near and distant cell-to-cell communication. Insight into this complex nanoscopic interaction in the development, progression and treatment of oral squamous cell carcinoma (OSCC) and precancerous oral mucosal disorders, termed oral potentially malignant disorders (OPMDs), remains of interest. In this review, we comprehensively present the current state of knowledge of EVs in OSCC and OPMDs. A systematic literature search strategy was developed and updated to December 17, 2019. Fifty-five articles were identified addressing EVs in OSCC and OPMDs with all but two articles published from 2015, highlighting the novelty of this research area. Themes included the impact of OSCC-derived EVs on phenotypic changes, lymph-angiogenesis, stromal immune response, mechanisms of therapeutic resistance as well as utility of EVs for drug delivery in OSCC and OPMD. Interest and progress of knowledge of EVs in OSCC and OPMD has been expanding on several fronts. The oral cavity presents a unique and accessible microenvironment for nanoparticle study that could present important models for other solid tumours. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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35 pages, 3551 KiB

Open AccessReview

Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

by Gabriella Schiera, Carlo Maria Di Liegro and Italia Di Liegro

Int. J. Mol. Sci. 2020, 21(1), 266; https://doi.org/10.3390/ijms21010266 - 30 Dec 2019

Cited by 42 | Viewed by 7633

Abstract

Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental [...] Read more.

Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now clear that glial cells, and in particular astrocytes, also play critical roles in both modes by releasing different kinds of molecules (e.g., D-serine secreted by astrocytes). On the other hand, neurons produce factors that can regulate the activity of glial cells, including their ability to release regulatory molecules. In the last fifteen years it has been demonstrated that both neurons and glial cells release extracellular vesicles (EVs) of different kinds, both in physiologic and pathological conditions. Here we discuss the possible involvement of EVs in the events underlying learning and memory, in both physiologic and pathological conditions. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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18 pages, 443 KiB

Open AccessReview

Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development

by Laurence Macia, Ralph Nanan, Elham Hosseini-Beheshti and Georges E. Grau

Int. J. Mol. Sci. 2020, 21(1), 107; https://doi.org/10.3390/ijms21010107 - 22 Dec 2019

Cited by 157 | Viewed by 11097

Abstract

Extracellular vesicles (EVs) are blebs of either plasma membrane or intracellular membranes carrying a cargo of proteins, nucleic acids, and lipids. EVs are produced by eukaryotic cells both under physiological and pathological conditions. Genetic and environmental factors (diet, stress, etc.) affecting EV cargo, [...] Read more.

Extracellular vesicles (EVs) are blebs of either plasma membrane or intracellular membranes carrying a cargo of proteins, nucleic acids, and lipids. EVs are produced by eukaryotic cells both under physiological and pathological conditions. Genetic and environmental factors (diet, stress, etc.) affecting EV cargo, regulating EV release, and consequences on immunity will be covered. EVs are found in virtually all body fluids such as plasma, saliva, amniotic fluid, and breast milk, suggesting key roles in immune development and function at different life stages from in utero to aging. These will be reviewed here. Under pathological conditions, plasma EV levels are increased and exacerbate immune activation and inflammatory reaction. Sources of EV, cells targeted, and consequences on immune function and disease development will be discussed. Both pathogenic and commensal bacteria release EV, which are classified as outer membrane vesicles when released by Gram-negative bacteria or as membrane vesicles when released by Gram-positive bacteria. Bacteria derived EVs can affect host immunity with pathogenic bacteria derived EVs having pro-inflammatory effects of host immune cells while probiotic derived EVs mostly shape the immune response towards tolerance. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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14 pages, 1031 KiB

Open AccessReview

Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Epithelial–Mesenchymal Transition

by Sevindzh Kletukhina, Olga Neustroeva, Victoria James, Albert Rizvanov and Marina Gomzikova

Int. J. Mol. Sci. 2019, 20(19), 4813; https://doi.org/10.3390/ijms20194813 - 27 Sep 2019

Cited by 30 | Viewed by 6528

Abstract

Epithelial–mesenchymal transition (EMT) is a process that takes place during embryonic development, wound healing, and under some pathological processes, including fibrosis and tumor progression. The molecular changes occurring within epithelial cells during transformation to a mesenchymal phenotype have been well studied. However, to [...] Read more.

Epithelial–mesenchymal transition (EMT) is a process that takes place during embryonic development, wound healing, and under some pathological processes, including fibrosis and tumor progression. The molecular changes occurring within epithelial cells during transformation to a mesenchymal phenotype have been well studied. However, to date, the mechanism of EMT induction remains to be fully elucidated. Recent findings in the field of intercellular communication have shed new light on this process and indicate the need for further studies into this important mechanism. New evidence supports the hypothesis that intercellular communication between mesenchymal stroma/stem cells (MSCs) and resident epithelial cells plays an important role in EMT induction. Besides direct interactions between cells, indirect paracrine interactions by soluble factors and extracellular vesicles also occur. Extracellular vesicles (EVs) are important mediators of intercellular communication, through the transfer of biologically active molecules, genetic material (mRNA, microRNA, siRNA, DNA), and EMT inducers to the target cells, which are capable of reprogramming recipient cells. In this review, we discuss the role of intercellular communication by EVs to induce EMT and the acquisition of stemness properties by normal and tumor epithelial cells. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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11 pages, 238 KiB

Open AccessReview

Challenges in Exosome Isolation and Analysis in Health and Disease

by Nils Ludwig, Theresa L. Whiteside and Torsten E. Reichert

Int. J. Mol. Sci. 2019, 20(19), 4684; https://doi.org/10.3390/ijms20194684 - 21 Sep 2019

Cited by 292 | Viewed by 17798

Abstract

A growing body of evidence emphasizes the important role exosomes in different physiological and pathological conditions. Exosomes, virus-size extracellular vesicles (EVs), carry a complex molecular cargo, which is actively processed in the endocytic compartment of parental cells. Exosomes carry and deliver this cargo [...] Read more.

A growing body of evidence emphasizes the important role exosomes in different physiological and pathological conditions. Exosomes, virus-size extracellular vesicles (EVs), carry a complex molecular cargo, which is actively processed in the endocytic compartment of parental cells. Exosomes carry and deliver this cargo to recipient cells, serving as an intercellular communication system. The methods for recovery of exosomes from supernatants of cell lines or body fluids are not uniformly established. Yet, studies of the quality and quantity of exosome cargos underlie the concept of “liquid biopsy.” Exosomes are emerging as a potentially useful diagnostic tool and a predictor of disease progression, response to therapy and overall survival. Although many novel approaches to exosome isolation and analysis of their cargos have been introduced, the role of exosomes as diagnostic or prognostic biomarkers of disease remains unconfirmed. This review considers existing challenges to exosome validation as disease biomarkers. Focusing on advantages and limitations of methods for exosome isolation and characterization, approaches are proposed to facilitate further progress in the development of exosomes as biomarkers in human disease. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

Other

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7 pages, 485 KiB

Open AccessOpinion

Microbe-Host Communication by Small RNAs in Extracellular Vesicles: Vehicles for Transkingdom RNA Transportation

by Heon-Jin Lee

Int. J. Mol. Sci. 2019, 20(6), 1487; https://doi.org/10.3390/ijms20061487 - 25 Mar 2019

Cited by 77 | Viewed by 6451

Abstract

Extracellular vesicles (EVs) are evolutionary well-conserved nano-sized membranous vesicles that are secreted by both prokaryotic and eukaryotic cells. Recently, they have gained great attention for their proposed roles in cell-to-cell communication, and as biomarkers for human disease. In particular, small RNAs (sRNAs) contained [...] Read more.

Extracellular vesicles (EVs) are evolutionary well-conserved nano-sized membranous vesicles that are secreted by both prokaryotic and eukaryotic cells. Recently, they have gained great attention for their proposed roles in cell-to-cell communication, and as biomarkers for human disease. In particular, small RNAs (sRNAs) contained within EVs have been considered as candidate interspecies-communication molecules, due to their demonstrated capacity to modulate gene expression in multiple cell types and species. While research into this field is in its infancy, elucidating the mechanisms that underlie host–microbe interactions and communications promises to impact many fields of biological research, including human health and medicine. Thus, this review discussed the results of recent studies that have examined the ways in which EVs and sRNAs mediate ‘microbe–host’ and ‘host–microbe’ interspecies communication. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Cell–Cell Communication)

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