scholarly journals In Vivo Tracking of Extracellular Vesicles by Nuclear Imaging: Advances in Radiolabeling Strategies

2020 ◽  
Vol 21 (24) ◽  
pp. 9443
Author(s):  
Sara Almeida ◽  
Liliana Santos ◽  
Amílcar Falcão ◽  
Célia Gomes ◽  
Antero Abrunhosa
Keyword(s):  
Extracellular Vesicles ◽  
Covalent Binding ◽  
Cell Communication ◽  
Nuclear Imaging ◽  
High Sensitivity ◽  
Imaging Modalities ◽  
Biological Behavior ◽  
Imaging Biomarkers ◽  
Special Focus

Extracellular vesicles (EVs) are naturally secreted vesicles that have attracted a large amount of interest in nanomedicine in recent years due to their innate biocompatibility, high stability, low immunogenicity, and important role in cell-to-cell communication during pathological processes. Their versatile nature holds great potential to improve the treatment of several diseases through their use as imaging biomarkers, therapeutic agents, and drug-delivery vehicles. However, the clinical translation of EV-based approaches requires a better understanding of their in vivo behavior. Several imaging technologies have been used for the non-invasive in vivo tracking of EVs, with a particular emphasis on nuclear imaging due to its high sensitivity, unlimited penetration depth and accurate quantification. In this article, we will review the biological function and inherent characteristics of EVs and provide an overview of molecular imaging modalities used for their in vivo monitoring, with a special focus on nuclear imaging. The advantages of radionuclide-based imaging modalities make them a promising tool to validate the use of EVs in the clinical setting, as they have the potential to characterize in vivo the pharmacokinetics and biological behavior of the vesicles. Furthermore, we will discuss the current methods available for radiolabeling EVs, such as covalent binding, encapsulation or intraluminal labeling and membrane radiolabeling, reporting the advantages and drawbacks of each radiolabeling approach.

scholarly journals Tiny Actors in the Big Cellular World: Extracellular Vesicles Playing Critical Roles in Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7688 ◽  
Author(s):  
Ancuta Jurj ◽  
Cecilia Pop-Bica ◽  
Ondrej Slaby ◽  
Cristina D. Ştefan ◽  
William C. Cho ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Recipient Cell ◽  
Cell Communication ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Cellular Functions ◽  
Membrane Bound

Communications among cells can be achieved either via direct interactions or via secretion of soluble factors. The emergence of extracellular vesicles (EVs) as entities that play key roles in cell-to-cell communication offer opportunities in exploring their features for use in therapeutics; i.e., management and treatment of various pathologies, such as those used for cancer. The potential use of EVs as therapeutic agents is attributed not only for their cell membrane-bound components, but also for their cargos, mostly bioactive molecules, wherein the former regulate interactions with a recipient cell while the latter trigger cellular functions/molecular mechanisms of a recipient cell. In this article, we highlight the involvement of EVs in hallmarks of a cancer cell, particularly focusing on those molecular processes that are influenced by EV cargos. Moreover, we explored the roles of RNA species and proteins carried by EVs in eliciting drug resistance phenotypes. Interestingly, engineered EVs have been investigated and proposed as therapeutic agents in various in vivo and in vitro studies, as well as in several clinical trials.

scholarly journals Molecular imaging perspectives

2005 ◽  
Vol 2 (3) ◽  
pp. 133-144 ◽  
Author(s):  
Paul J Cassidy ◽  
George K Radda
Keyword(s):  
Molecular Imaging ◽  
Contrast Agents ◽  
Physical Science ◽  
Life Science ◽  
Interdisciplinary Collaboration ◽  
Nuclear Imaging ◽  
Imaging Modalities ◽  
Molecular Events ◽  
Biological Target

Molecular imaging is an emerging technology at the life science/physical science interface which is set to revolutionize our understanding and treatment of disease. The tools of molecular imaging are the imaging modalities and their corresponding contrast agents. These facilitate interaction with a biological target at a molecular level in a number of ways. The diverse nature of molecular imaging requires knowledge from both the life and physical sciences for its successful development and implementation. The aim of this review is to introduce the subject of molecular imaging from both life science and physical science perspectives. However, we will restrict our coverage to the prominent in vivo molecular imaging modalities of magnetic resonance imaging, optical imaging and nuclear imaging. The physical basis of these imaging modalities, the use of contrast agents and the imaging parameters of sensitivity, temporal resolution and spatial resolution are described. Then, the specificity of contrast agents for targeting and sensing molecular events, and some applications of molecular imaging in biology and medicine are given. Finally, the diverse nature of molecular imaging and its reliance on interdisciplinary collaboration is discussed.

scholarly journals Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunfei Ma ◽  
Takeshi Yoshida ◽  
Kazutaka Matoba ◽  
Katsuhiko Kida ◽  
Rito Shintani ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Detection System ◽  
Cell Communication ◽  
Human Mesenchymal Stem Cells ◽  
High Sensitivity ◽  
Elisa System ◽  
Highly Sensitive ◽  
High Throughput Method ◽  
Cellular Specificity

AbstractExtracellular vesicles (EVs) are secreted from most cells and play important roles in cell–cell communication by transporting proteins, lipids, and nucleic acids. As the involvement of EVs in diseases has become apparent, druggable regulators of EV secretion are required. However, the lack of a highly sensitive EV detection system has made the development of EV regulators difficult. We developed an ELISA system using a high-affinity phosphatidylserine-binder TIM4 to capture EVs and screened a 1567-compound library. Consequently, we identified one inhibitor and three activators of EV secretion in a variety of cells. The inhibitor, apoptosis activator 2, suppressed EV secretion via a different mechanism and had a broader cellular specificity than GW4869. Moreover, the three activators, namely cucurbitacin B, gossypol, and obatoclax, had broad cellular specificity, including HEK293T cells and human mesenchymal stem cells (hMSCs). In vitro bioactivity assays revealed that some regulators control EV secretion from glioblastoma and hMSCs, which induces angiogenesis and protects cardiomyocytes against apoptosis, respectively. In conclusion, we developed a high-throughput method to detect EVs with high sensitivity and versatility, and identified four compounds that can regulate the bioactivity of EVs.

scholarly journals Radioiodine labeling and in vivo trafficking of extracellular vesicles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chae Moon Hong ◽  
Prakash Gangadaran ◽  
Ji Min Oh ◽  
Ramya Lakshmi Rajendran ◽  
Arunnehru Gopal ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Extracellular Vesicles ◽  
Intravenous Injection ◽  
Gamma Camera ◽  
Imaging System ◽  
Ex Vivo ◽  
Nuclear Imaging ◽  
Significant Difference ◽  
Before And After

AbstractBiodistribution and role of extracellular vesicles (EVs) are still largely unknown. Reliable tracking methods for EVs are needed. In this study, nuclear imaging using radioiodine were developed and applied for tracking EVs derived from cell lines. EVs were obtained from supernatant of thyroid cancer cell (Cal62) and natural killer cells (NK92-MI) using sequential ultracentrifuges. Sulfosuccinimidyl-3-(4-hydroxypheynyl) propionate were labeled to membrane of Cal62 and NK92-MI cell derived EVs, then the EVs were labeled with radioiodine (I-131 and I-125) using pre-coated iodination tubes (RI-EVs). In vivo gamma camera images were obtained after intravenous injection of the RI-EVs, and ex vivo biodistribution study was also performed. EVs were labeled with radioiodine and radiochemical purity of the RI-EV was more than 98%. Results of nanoparticle tracking analysis and electron microscopy showed that there was no significant difference in EVs before and after the radioiodine labeling. After intravenous injection of RI-EVs to mice, gamma camera imaging well visualized the real-time biodistribution of the RI-EVs. RI-EVs were mainly visualized at liver, spleen, and lung. Nuclear imaging system of EVs derived from thyroid cancer and NK cells using radioiodine labeling of the EVs was established. Thus, this system might be helpful for in vivo tracking of EVs.

scholarly journals Beyond the Extracellular Vesicles: Technical Hurdles, Achieved Goals and Current Challenges When Working on Adipose Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3362
Author(s):  
María Gómez-Serrano ◽  
Viviane Ponath ◽  
Christian Preußer ◽  
Elke Pogge von Strandmann
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Special Focus ◽  
Entire Body ◽  
Main Cell ◽  
Systemic Level ◽  
Main Cell Type ◽  
Methodological Approaches ◽  
Adipose Cells

Adipose tissue and its crosstalk with other organs plays an essential role in the metabolic homeostasis of the entire body. Alteration of this communication (i.e., due to obesity) is related to the development of several comorbidities including type 2 diabetes, cardiovascular diseases, or cancer. Within the adipose depot, adipocytes are the main cell type and thus the main source of secreted molecules, which exert modulating effects not only at a local but also at a systemic level. Extracellular vesicles (EVs) have recently emerged as important mediators in cell–cell communication and account for part of the cellular secretome. In recent years, there has been a growing body of research on adipocyte-derived extracellular vesicles (Ad-EVs). However, there is still a lack of standardized methodological approaches, especially regarding primary adipocytes. In this review, we will provide an outline of crucial aspects when working on adipose-derived material, with a special focus on primary adipocytes. In parallel, we will point out current methodological challenges in the EV field and how they impact the transcriptomic, proteomic and functional evaluations of Ad-EVs.

scholarly journals A System of Cytokines Encapsulated in ExtraCellular Vesicles

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Wendy Fitzgerald ◽  
Michael L. Freeman ◽  
Michael M. Lederman ◽  
Elena Vasilieva ◽  
Roberto Romero ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Ex Vivo ◽  
Biological Effects ◽  
Cell Communication ◽  
Health And Disease ◽  
Mediate Cell ◽  
Multicellular Organisms ◽  
Cell Cell

Abstract Cytokines are soluble factors that mediate cell–cell communications in multicellular organisms. Recently, another system of cell–cell communication was discovered, which is mediated by extracellular vesicles (EVs). Here, we demonstrate that these two systems are not strictly separated, as many cytokines in vitro, ex vivo, and in vivo are released in EV-encapsulated forms and are capable of eliciting biological effects upon contact with sensitive cells. Association with EVs is not necessarily a property of a particular cytokine but rather of a biological system and can be changed upon system activation. EV-encapsulated cytokines were not detected by standard cytokine assays. Deciphering the regulatory mechanisms of EV-encapsulation will lead to a better understanding of cell–cell communications in health and disease.

scholarly journals T cell-derived extracellular vesicles are elevated in essential HTN

2020 ◽  
Vol 319 (5) ◽  
pp. F868-F875
Author(s):  
Sabrina La Salvia ◽  
Luca Musante ◽  
Joanne Lannigan ◽  
Joseph Christopher Gigliotti ◽  
Thu H. Le ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Kidney Tissue ◽  
Cell Communication ◽  
Organ Damage ◽  
In Vivo Model ◽  
Ang Ii

Extracellular vesicles (EVs) are novel mediators of cell-to-cell communication and appear to mediate the pathogenesis of hypertension (HTN). However, the mechanisms underlying the involvement of EVs in HTN remain unclear. The adaptive and innate immune systems play an important role affecting the kidney and vasculature in animal models of HTN. Evolving evidence shows that immune cell-derived EVs can modulate the immune system in a paracrine fashion and therefore may mediate the effects of inflammation in the pathogenesis of HTN. Therefore, we aimed to understand if specific subtypes of leukocyte/immune cell-derived EVs are altered in essential HTN using an in vivo model of angiotensin II (ANG II)-induced HTN. After 4 wk of ANG II treatment, EVs were isolated from the blood and kidney. EV origin and counts were characterized with Imaging Flow Cytometry, antibody panels targeting platelets, endothelial cells, and leukocytes including B and T cells, monocytes, and neutrophils. Leukocyte-derived EVs (CD45+) were elevated in the circulation and kidney tissue in ANG II-induced HTN. Subgroup analysis depicted T cell-derived EVs (CD3+) to be significantly elevated in ANG II-induced HTN (3.50 e+5 particles/mL) compared with control groups (9.16 e+4 particles/mL, P = 0.0106). T cell-derived EVs also significantly correlated with systolic blood pressure levels ( r2 = 0.898, P = 0.0012). In summary, leukocyte-derived EVs, and more specifically T cell-derived EVs (CD3+), are elevated in ANG II-induced HTN in the circulation and kidney tissue and correlate well with blood pressure severity. EVs from the circulation and kidney may be sensitive biomarkers for HTN and end-organ damage and may lead to new mechanistic insights in this silent disease.

scholarly journals In vivo imaging and tracking of exosomes for theranostics

2021 ◽  
pp. 2130005
Author(s):  
Ning Ma ◽  
Changfeng Wu ◽  
Zihui Meng
Keyword(s):  
Clinical Application ◽  
In Vivo Imaging ◽  
Photoacoustic Imaging ◽  
Imaging Techniques ◽  
Cell Communication ◽  
Nuclear Imaging ◽  
Future Research ◽  
Uptake Mechanism ◽  
Lipid Bilayer Vesicles

Exosomes are lipid bilayer vesicles released by cells and serve as natural carriers for cell–cell communication. Exosomes provide a promising approach to the diagnosis and treatment of diseases and are considered as an alternative to cell therapy. However, one main restriction in their clinical application is that the current understanding of these vesicles, especially their in vivo behaviors and distributions, remains inadequate. Here, we reviewed the current and emerging methods for in vivo imaging and tracking of exosomes, including fluorescence imaging, bioluminescence imaging, nuclear imaging, X-ray imaging, magnetic resonance imaging, photoacoustic imaging, and multimodal imaging. In vivo imaging and tracking of exosomes by these methods can help researchers further understand their uptake mechanism, biodistribution, migration, function, and therapeutic performance. The pioneering studies in this field can elucidate many unknown exosomal behaviors at different levels. We discussed the advantages and limitations of each labeling and imaging strategy. The advances in labeling and in vivo imaging will expand our understanding of exosomes and promote their clinical application. We finally provide a perspective and discuss several important issues that need to be explored in future research. This review highlights the values of efficient, sensitive, and biocompatible exosome labeling and imaging techniques in disease theranostics.

scholarly journals Extracellular Vesicles From 3xTg-AD Mouse and Alzheimer’s Disease Patient Astrocytes Impair Neuroglial and Vascular Components

2021 ◽  
Vol 13 ◽  
Author(s):  
Luis Alfonso González-Molina ◽  
Juan Villar-Vesga ◽  
Julián Henao-Restrepo ◽  
Andrés Villegas ◽  
Francisco Lopera ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Neurovascular Unit ◽  
Disease Patient ◽  
Cell Communication ◽  
Adult Mice ◽  
Essential Components ◽  
Endothelial Cell Death ◽  
Cell Cell

Astrocytes are specialized glial cells that are essential components of the neurovascular unit (NVU) and are involved in neurodevelopment, brain maintenance and repair, and neurodegeneration. Astrocytes mediate these processes by releasing cellular mediators such as extracellular vesicles (EVs). EVs are vehicles of cell-cell communication and have been proposed as mediators of damage in AD. However, the transcellular mechanism by which Alzheimer disease (AD) astrocytes impair the function of NVU components is poorly understood. Therefore, we evaluated the effects of adult PS1-KI and 3xTg-AD astrocyte conditioned media (CM) and EVs on NVU components (neuroglia and endothelium) in vitro. Additionally, SAD and FAD astrocyte-derived EVs (A-EVs) were characterized, and we evaluated their effects on NVU in cocultured cells in vitro and on intrahippocampal CA1 cells in vivo. Surprisingly, cultured 3xTg-AD astrocytes showed increased glial fibrillary acidic protein (GFAP) reactivity compared to PS1-KI astrocytes, which denotes astrocytic hyperreactivity. CM from adult mice 3xTg-AD astrocytes increased cell-cell gaps between endothelial cells, filopodia-like dendritic protrusions in neurons and neuronal and endothelial cell death. 3xTg-AD A-EVs induced neurotoxicity and increased astrocyte GFAP reactivity. Cultured human postmortem astrocytes from AD patients also increased GFAP reactivity and EVs release. No differences in the size or number of A-EVs were detected between AD and control samples; however, both SAD and FAD A-EVs showed increased expression of the surface marker aquaporin 4. A-EVs induced cytotoxicity and astrocyte hyperactivation: specifically, FAD A-EVs induced neuroglial cytotoxicity and increased gaps between the endothelium, while SAD A-EVs mainly altered the endothelium. Similarly, both AD A-EVs increased astrocyte GS reactivity and vascular deterioration in vivo. We associated this finding with perivascular reactive astrocytes and vascular deterioration in the human AD brain. In summary, these results suggest that AD A-EVs impair neuroglial and vascular components.

scholarly journals 3D Cell Cultures as Prospective Models to Study Extracellular Vesicles in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 307
Author(s):  
Guillermo Bordanaba-Florit ◽  
Iratxe Madarieta ◽  
Beatriz Olalde ◽  
Juan M. Falcón-Pérez ◽  
Félix Royo
Keyword(s):  
Extracellular Vesicles ◽  
3D Culture ◽  
Cell Communication ◽  
Drug Carriers ◽  
Antitumoral Activity ◽  
Potential Applications ◽  
Culture Models ◽  
Stem Cell Populations ◽  
Promising Source

The improvement of culturing techniques to model the environment and physiological conditions surrounding tumors has also been applied to the study of extracellular vesicles (EVs) in cancer research. EVs role is not only limited to cell-to-cell communication in tumor physiology, they are also a promising source of biomarkers, and a tool to deliver drugs and induce antitumoral activity. In the present review, we have addressed the improvements achieved by using 3D culture models to evaluate the role of EVs in tumor progression and the potential applications of EVs in diagnostics and therapeutics. The most employed assays are gel-based spheroids, often utilized to examine the cell invasion rate and angiogenesis markers upon EVs treatment. To study EVs as drug carriers, a more complex multicellular cultures and organoids from cancer stem cell populations have been developed. Such strategies provide a closer response to in vivo physiology observed responses. They are also the best models to understand the complex interactions between different populations of cells and the extracellular matrix, in which tumor-derived EVs modify epithelial or mesenchymal cells to become protumor agents. Finally, the growth of cells in 3D bioreactor-like systems is appointed as the best approach to industrial EVs production, a necessary step toward clinical translation of EVs-based therapy.

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