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Anna Picca, Flora Guerra, Riccardo Calvani, Cecilia Bucci, Maria Rita Lo Monaco, Anna Rita Bentivoglio, Hélio José Coelho-Júnior, Francesco Landi, Roberto Bernabei, Emanuele Marzetti
The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient sensing, epigenetic alterations, and stem cell exhaustion have been proposed as hallmarks of aging. These "aging pillars" are not mutually exclusive, making the matter intricate and leaving numerous unanswered questions...
February 13, 2019: International Journal of Molecular Sciences
Federico Cocozza, Florencia Menay, Rodrigo Tsacalian, Analía Elisei, Pura Sampedro, Ivana Soria, Claudia Waldner, María José Gravisaco, Claudia Mongini
Exosomes are 60-150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic drugs, hypoxia, acidosis, or radiation by increasing the release of EVs. In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly increased EVs yield...
February 15, 2019: Vaccine
Yongbin Ma, Liyang Dong, Dan Zhou, Li Li, Wenzhe Zhang, Yu Zhen, Ting Wang, Jianhua Su, Deyu Chen, Chaoming Mao, Xuefeng Wang
Peripheral nerve injury results in limited nerve regeneration and severe functional impairment. Mesenchymal stem cells (MSCs) are a remarkable tool for peripheral nerve regeneration. The involvement of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) in peripheral nerve regeneration, however, remains unknown. In this study, we evaluated functional recovery and nerve regeneration in rats that received hUCMSC-EV treatment after nerve transection. We observed that hUCMSC-EV treatment promoted the recovery of motor function and the regeneration of axons; increased the sciatic functional index; resulted in the generation of numerous axons and of several Schwann cells that surrounded individual axons; and attenuated the atrophy of the gastrocnemius muscle...
February 17, 2019: Journal of Cellular and Molecular Medicine
Rebecca M Wadey, Katherine D Connolly, Donna Mathew, Gareth Walters, D Aled Rees, Philip E James
BACKGROUND AND AIMS: Obesity is associated with an increased risk of cardiovascular disease, but the mechanisms involved are not completely understood. In obesity, the adipocyte microenvironment is characterised by both hypoxia and inflammation. Therefore, we sought to determine whether extracellular vesicles (EVs) derived from adipocytes in this setting might be involved in mediating cardiovascular disease, specifically by promoting leukocyte attachment to vascular endothelial cells...
January 24, 2019: Atherosclerosis
Jinni Hong, Owais M Bhat, Guangbi Li, Sara K Dempsey, Qinghua Zhang, Joseph K Ritter, Weiwei Li, Pin-Lan Li
The NLRP3 inflammasome is activated in the cytoplasm of cells and its products such as IL-1β are exported through a non-classical ER-Golgi pathway. Several mechanistically distinct models including exocytosis of secretory lysosomes, microvesicles (MVs) and extracellular vehicles (EVs) have been proposed for their release. In this study, we hypothesized that the NLRP3 inflammasome product, IL-1β in response to exogenously administrated and endogenously produced d-ribose stimulation is released via extracellular vesicles including EVs via a sphingolipid-mediated molecular mechanisms controlling lysosome and multivesicular body (MVB) interaction...
February 13, 2019: Biochimica et biophysica acta. Molecular cell research
Patrycja Przygodzka, Izabela Papiewska-Pająk, Helena Bogusz-Koziarska, Ewelina Sochacka, Joanna Boncela, M Anna Kowalska
Epithelial-to-mesenchymal transition (EMT) in cancer cells, represents early stages of metastasis and is a promising target in colorectal cancer (CRC) therapy. There have been many attempts to identify markers and key pathways induced throughout EMT but the process is complex and depends on the cancer type and tumour microenvironment. Here we used the colon cancer cell line HT29, which stably overexpressed Snail, the key transcription factor in early EMT, as a model for colorectal adenocarcinoma cells with a pro-metastatic phenotype...
February 15, 2019: Scientific Reports
Fanghui Zhang, Rongrong Li, Yunshan Yang, Chunhui Shi, Yingying Shen, Chaojie Lu, Yinghu Chen, Wu Zhou, Aifu Lin, Lei Yu, Wanjing Zhang, Zhenwei Xue, Jianli Wang, Zhijian Cai
Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19+ extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8+ T cell responses. Serum CD19+ EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19+ EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1α (HIF-1α) promoted B cells to release CD19+ EVs by inducing Rab27a mRNA transcription...
February 6, 2019: Immunity
Jiao Jiao Li, Elham Hosseini-Beheshti, Georges E Grau, Hala Zreiqat, Christopher B Little
Extracellular vesicles (EVs) are nanoscale particles secreted by almost all cell types to facilitate intercellular communication. Stem cell-derived EVs theoretically have the same biological functions as stem cells, but offer the advantages of small size, low immunogenicity, and removal of issues such as low cell survival and unpredictable long-term behaviour associated with direct cell transplantation. They have been an area of intense interest in regenerative medicine, due to the potential to harness their anti-inflammatory and pro-regenerative effects to induce healing in a wide variety of tissues...
February 14, 2019: Nanomaterials
Eline Oeyen, Lucien Hoekx, Stefan De Wachter, Marcella Baldewijns, Filip Ameye, Inge Mertens
Diagnostic methods currently used for bladder cancer are cystoscopy and urine cytology. Cystoscopy is an invasive tool and has low sensitivity for carcinoma in situ. Urine cytology is non-invasive, is a low-cost method, and has a high specificity but low sensitivity for low-grade urothelial tumors. Despite the search for urinary biomarkers for the early and non-invasive detection of bladder cancer, no biomarkers are used at the present in daily clinical practice. Extracellular vesicles (EVs) have been recently studied as a promising source of biomarkers because of their role in intercellular communication and tumor progression...
February 14, 2019: International Journal of Molecular Sciences
Byron Miyazawa, Alpa Trivedi, Padma Priya Togarrati, Daniel Potter, Gyulnar Baimukanova, Lindsay Vivona, Maximillian Lin, Ernesto Lopez, Rachael Callcut, Amit K Srivastava, Lucy Z Kornblith, Alexander T Fields, Martin A Schreiber, Charles E Wade, John B Holcomb, Shibani Pati
BACKGROUND: Platelet (Plt) derived-extracellular vesicles (Plt-EVs) have hemostatic properties similar to Plts. In addition to hemostasis, Plts also function to stabilize the vasculature and maintain endothelial cell (EC) barrier integrity. We hypothesized that Plt-EVs would inhibit vascular endothelial cell permeability, similar to fresh Plts. To investigate this hypothesis we utilized in vitro and in vivo models of vascular endothelial compromise and bleeding. METHODS: In vitro: Plt-EVs were isolated by ultracentrifugation and characterized for Plt markers and particle size distribution...
February 13, 2019: Journal of Trauma and Acute Care Surgery
Anna Bång-Rudenstam, Myriam Cerezo-Magaña, Mattias Belting
Although the overall mortality in cancer is steadily decreasing, major groups of patients still respond poorly to available treatments. The key clinical challenge discussed here relates to the inherent capacity of cancer cells to metabolically adapt to hypoxic and acidic stress, resulting in treatment resistance and a pro-metastatic behavior. Hence, a detailed understanding of stress adaptive responses is critical for the design of more rational therapeutic strategies for cancer. We will focus on the emerging role of extracellular vesicles (EVs) and lipoprotein particles in cancer cell metabolic stress adaptation and how these pathways may constitute potential Achilles' heels of the cancer cell machinery and alternative treatment targets of metastasis...
February 15, 2019: Cancer Metastasis Reviews
Jesus M Banales, Ariel E Feldstein, Hanna Sänger, Veronika Lukacs-Kornek, Gyongyi Szabo, Miroslaw Kornek
Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by cells and found in all biological fluids. They are effective intercellular communicators, acting on a number of close and/or distant target cells. EV cargo may reflect the cell of origin as well as the specific stress that induces their formation and release. They transport a variety of bioactive molecules, including messenger RNA, noncoding RNAs, proteins, lipids, and metabolites, that can be transferred among cells, regulating various cell responses...
February 2019: Hepatology Communications
Carmen Campos-Silva, Henar Suárez, Ricardo Jara-Acevedo, Estefanía Linares-Espinós, Luis Martinez-Piñeiro, María Yáñez-Mó, Mar Valés-Gómez
Extracellular vesicles (EVs) provide an invaluable tool to analyse physiological processes because they transport, in biological fluids, biomolecules secreted from diverse tissues of an individual. EV biomarker detection requires highly sensitive techniques able to identify individual molecules. However, the lack of widespread, affordable methodologies for high-throughput EV analyses means that studies on biomarkers have not been done in large patient cohorts. To develop tools for EV analysis in biological samples, we evaluated here the critical parameters to optimise an assay based on immunocapture of EVs followed by flow cytometry...
February 14, 2019: Scientific Reports
Sadhna O Piryani, Yiqun Jiao, Angel Y F Kam, Yang Liu, Tuan Vo-Dinh, Benny J Chen, Nelson J Chao, Phuong L Doan
PURPOSE: Extracellular vesicles (EVs) are shed vesicles that bear a combination of nucleic acids and proteins. EVs are becoming recognized as a mode of cell-to-cell communication. Since hematopoietic stem cells (HSCs) reside in proximity to endothelial cells (ECs), we investigated whether EC-derived EVs could regulate HSC regeneration following ionizing radiation. METHODS AND MATERIALS: We generated EVs derived from primary murine marrow ECs. We sought to determine the response of irradiated hematopoietic stem and progenitor cells to syngeneic or allogeneic EVs in culture assays...
February 11, 2019: International Journal of Radiation Oncology, Biology, Physics
Uma Thanigai Arasu, Kai Härkönen, Arto Koistinen, Kirsi Rilla
Extracellular vesicles (EVs) and their interactions with recipient cells constitute a rapidly growing research area. However, due to the limitations in current methodologies, the mechanisms of these interactions are still unclear. Microscopic studies of EVs are challenging, because their typical diameter is near the resolution limit of light microscopy, and electron microscopy has restricted possibilities for protein labelling. The objective of this study was to combine these two techniques to demonstrate in detail the interactions of EVs by recipient cells...
February 11, 2019: Experimental Cell Research
Sarah L Sayner, Chung-Sik Choi, Marcy E Maulucci, Ramila Kc, Chun Zhou, April K Scruggs, Thomas Yarbrough, Leslie Anne Hargett Blair, Judy A C King, Roland Seifert, Volkhard Kaever, Natalie N Bauer
The second messenger, cAMP, is highly compartmentalized to facilitate signaling specificity. Extracellular vesicles (EVs) are submicron, intact vesicles released from many cell types that can act as biomarkers or be involved in cell-to-cell communication. While it is well recognized that EVs encapsulate functional proteins and RNAs/miRNAs, currently it is unclear whether cyclic nucleotides are encapsulated within EVs to provide an additional second messenger compartment. Using ultracentrifugation, EVs were isolated from the culture medium of unstimulated systemic and pulmonary endothelial cells...
February 13, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Marcos Jun-Iti Yokoo, Leonardo de Oliveira Seno, Luiza Corrêa Oliveira, Pedro U N da Costa, Gustavo M da Silva, Renata W Suñé, Fernando Flores Cardoso
This study aimed to calculate economic values (EVs) and economic selection indices for milk production systems in small rural properties. The traits 305-d milk yield in kg (MY), fat (FP) and protein (PP) percentage, daily fat (FY) and protein (PY) yield, cow live weight in kg (LW), calving interval (CI), and logarithm of daily somatic cell count (SCC) in milk were considered the goals and selection criteria. The production systems were identified from 29 commercial properties based on the inventory of revenues and costs and of zootechnical field data...
February 13, 2019: Journal of Dairy Research
Jacopo Meldolesi
Two types of extracellular vesicles (EVs), exosomes and ectosomes, are generated and released by all cells, including immune cells. The two EVs appear different in many properties: size, mechanism and site of assembly, composition of their membranes and luminal cargoes, sites and processes of release. In functional terms, however, these differences are minor. Moreover, their binding to and effects on target cells appear similar thus the two types are considered distinct only in a few cases, otherwise they are presented together as EVs...
February 13, 2019: Clinical and Experimental Immunology
Lina Antounians, Areti Tzanetakis, Ornella Pellerito, Vincenzo D Catania, Adrienne Sulistyo, Louise Montalva, Mark J McVey, Augusto Zani
Extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs) mediate anti-apoptotic, pro-angiogenic, and immune-modulatory effects in multiple disease models, such as skeletal muscle atrophy and Alport syndrome. A source of potential variability in EV biological functions is how EV are isolated from parent cells. Currently, a comparative study of different EV isolation strategies using conditioned medium from AFSCs is lacking. Herein, we examined different isolation strategies for AFSC-EVs, using common techniques based on differential sedimentation (ultracentrifugation), solubility (ExoQuick, Total Exosome Isolation Reagent, Exo-PREP), or size-exclusion chromatography (qEV)...
February 12, 2019: Scientific Reports
Mengmeng Zhao, Asuka Nanbo, Lichun Sun, Zhen Lin
Extracellular vesicles (EVs), including exosomes and microvesicles, are evolutionarily conserved phospholidpid membrane-bound entities secreted from most eukaryotic cell types. They carry bioactive cargos such as protein and nucleic acids derived from their cells of origin. Over the past 10 years, they have been attracting increased attention in many fields of life science, representing a new route for intercellular communication. In this review article, we will discuss the current knowledge of both normal and virally modified EVs in the regulation of Epstein-Barr virus (EBV)'s life cycle and its associated pathogenesis...
February 11, 2019: Microorganisms
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