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Rafael Almeida Paiva, Tania Martins-Marques, Katia Jesus, Teresa Ribeiro-Rodrigues, Monica Zuzarte, Ana Silva, Liliana Reis, Maria da Silva, Paulo Pereira, Pieter Vader, Joost Petrus Gerardus Sluijter, Lino Gonçalves, Maria Teresa Cruz, Henrique Girao
Myocardial ischaemia is associated with an exacerbated inflammatory response, as well as with a deregulation of intercellular communication systems. Macrophages have been implicated in the maintenance of heart homeostasis and in the progression and resolution of the ischaemic injury. Nevertheless, the mechanisms underlying the crosstalk between cardiomyocytes and macrophages remain largely underexplored. Extracellular vesicles (EVs) have emerged as key players of cell-cell communication in cardiac health and disease...
December 4, 2018: Journal of Cellular and Molecular Medicine
Tatiana Lopatina, Enrica Favaro, Cristina Grange, Massimo Cedrino, Andrea Ranghino, Sergio Occhipinti, Sofia Fallo, Fabrizio Buffolo, Daria A Gaykalova, Maria M Zanone, Renato Romagnoli, Giovanni Camussi
We previously have shown that platelet-derived growth factor (PDGF) modulates the biological activity of extracellular vesicles released by adipose-derived mesenchymal stem cells (ASC-EVs). ASC-EVs may interact with blood and vessel cells by transferring proteins and nucleic acids and regulate their functions. In this study, we investigated immunomodulatory activity and protection from acute hindlimb ischemia of EVs released by PDGF-stimulated ASC (PDGF-EVs). PDGF treatment of ASC changed protein and RNA composition of released EVs by enhancing the expression of anti-inflammatory and immunomodulatory factors...
December 4, 2018: Scientific Reports
Gonzalo Almanza, Jeffrey J Rodvold, Brian Tsui, Kristen Jepsen, Hannah Carter, Maurizio Zanetti
The successful implementation of miRNA (miR) therapies in humans will ultimately rely on the use of vehicles with improved cellular delivery capability. Here we tested a new system that leverages extracellular vesicles (EVs) laden with a tumor suppressor miRNA (miR-335) produced in B cells by plasmid DNA induction (iEVs). We demonstrate that iEVs-335 efficiently and durably restored the endogenous miR-335 pool in human triple negative breast cancer cells, downregulated the expression of the miR-335 target gene SOX4 transcription factor, and markedly inhibited tumor growth in vivo...
December 4, 2018: Scientific Reports
Hyejong Kang, Myung-Ju Lee, Sang June Park, Myung-Shin Lee
Periodontitis is a common disease characterized by chronic inflammation and tissue destruction of gums. Human periodontal ligament stem cells (PDLSCs), derived from the periodontium, have stem cell properties similar to those of mesenchymal stem cells. PDLSCs possess not only the potential to differentiate into other tissues, but also immunomodulatory abilities. Macrophages play a critical role in periodontal disease, but little is known regarding the role of PDLSCs in macrophage modulation during inflammation...
December 3, 2018: International Journal of Molecular Sciences
Duško Lainšček, Lucija Kadunc, Mateja Manček-Keber, Iva Hafner-Bratkovič, Rok Romih, Roman Jerala
The CRISPR/Cas system has been developed as a potent tool for genome engineering and transcription regulation. However, the efficiency of its delivery into cells, particularly for therapeutic in vivo applications, remains a major bottleneck. Extracellular vesicles (EVs), released by eukaryotic cells, can mediate the transfer of different molecules, including nucleic acids and proteins. Here we show packaging and delivery of the CRISPR/Cas system via EVs to target cells, combining the advantages of both technological platforms...
December 4, 2018: ACS Synthetic Biology
Jihyun Kim, Jaewang Lee, Tae Bok Lee, Jin Hyun Jun
Recently, many studies have investigated the role of extracellular vesicles (EVs) on reproductive events, including embryo development and death, oviduct-embryo crosstalk, in vitro fertilization and others. The aim of this study was to demonstrate whether outgrowth embryo-derived EVs function as bioactive molecules and regulate mouse embryonic developmental competence in vitro and implantation potential in utero. The EVs from mouse outgrowth embryos on 7.5 days post-coitum were detected and selectively isolated to evaluate the embryotrophic functions on pre-implantation embryos...
December 4, 2018: Molecular Reproduction and Development
Sergio Montaner-Tarbes, Elena Novell, Vicens Tarancón, Francesc E Borrás, Maria Montoya, Lorenzo Fraile, Hernando A Del Portillo
The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the etiological agent of one of the most important swine diseases with a significant economic burden worldwide. Unfortunately, available vaccines are partially effective highlighting the need of novel approaches. Previously, antigenic viral proteins were described in serum-derived extracellular vesicles (EVs) from pigs previously infected with PRRSV. Here, a targeted-pig trial was designed to determine the safety and immunogenicity of such extracellular vesicles enriched fractions...
November 30, 2018: Scientific Reports
Carolina Coelho, Lisa C Brown, Maria Maryam, Raghav Vij, Daniel Fq Smith, Meagan C Burnet, Jennifer E Kyle, Heino M Heyman, Jasmine Ramirez, Rafael Prados-Rosales, Gregoire Lauvau, Ernesto S Nakayasu, Nathan R Brady, Anne Hamacher-Brady, Isabelle Coppens, Arturo Casadevall
Outer membrane vesicles produced by Gram-negative bacteria have been studied for half a century but the possibility that Gram-positive bacteria secreted extracellular vesicles (EVs) was not pursued until recently due to the assumption that the thick peptidoglycan cell wall would prevent their release to the environment. However, following their discovery in fungi, which also have cell walls, EVs have now been described for a variety of Gram-positive bacteria. EVs purified from Gram-positive bacteria are implicated in virulence, toxin release and transference to host cells, eliciting immune responses, and spread of antibiotic resistance...
November 30, 2018: Journal of Biological Chemistry
Razieh Dalirfardouei, Khadijeh Jamialahmadi, Elahe Mahdipour
BACKGROUND: Mesenchymal stem cells (MSCs) are currently the most promising candidates in regenerative medicine. Nonetheless, there are several limitations associated with the MSC tissue source such as infrequent and invasive bone marrow sampling methods. To overcome these limitations, we have procured MSCs from the menstrual blood (MenSCs) as a non-invasive source using a straightforward and cost-effective method. Moreover, we isolated MenSCs-derived exosomes as a safe and highly effective approach to exert the paracrine effects of MSCs...
December 2018: Tissue & Cell
Haiyan Liu, Matt Kang, Julie Wang, Cherie Blenkiron, Arier Lee, Michelle Wise, Larry Chamley, Qi Chen
BACKGROUND: The human placenta extrudes a variety of extracellular vesicles (EVs) into the maternal blood daily. These vesicles may be crucial to the adaptation of the maternal cardiovascular and immune systems to pregnancy. Quantifying the EVs that are released in early gestation is important to our understanding of how placental EVs may contribute to the regulation of maternal physiology. METHODS: EVs were isolated from first trimester placental explants and separated into micro- and nano-vesicles by differential centrifugation...
December 2018: Placenta
Cong Ma, Qing-Yi Zang, Zi-Kuan Guo, Heng-Xiang Wang
OBJECTIVE: To investigate the effect of immune regulatory molecules TGF-β1 and IL-10 on the immunoregulatory activities of extracellular vesicles(EV) secreted from mesenchymal stem cells (MSCs). METHODS: MSC were isolated from human umbilical cord and expanded, then were treated with TGF-β1 and IL-10 for 72h, and MSC-EVs in supernatants were isolated. The total protein content of all samples was determined by BCA methed. The morphological structure was observed by transmission electron microscopy...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Hyun-Kyung Woo, Juhee Park, Ja Yoon Ku, Chan Ho Lee, Vijaya Sunkara, Hong Koo Ha, Yoon-Kyoung Cho
Androgen-receptor splice variant 7 (AR-V7) is associated with castration-resistant prostate cancer (CRPC) and resistance to anti-androgen therapy. Despite its clinical importance, the lack of efficient methods for AR-V7 analysis remains a challenge for broader use of this biomarker in routine clinical practice. Herein, we suggest a practical and non-invasive liquid biopsy method for analysis of AR-V7 in the RNA of urine-derived extracellular vesicles (EVs) without the need for blood withdrawal. Urine-derived EVs were isolated by a lab-on-a-disc integrated with six independent nanofiltration units (Exo-Hexa) allowing simultaneous processing of six individual samples...
November 30, 2018: Lab on a Chip
Yang Liu, Zhuyuan Liu, Yuan Xie, Cuimei Zhao, Jiahong Xu
Extracellular vesicles (EVs) are small-sized membrane-surrounded structures released from cells into the blood, which play important roles in regulating various biological processes. However, the role of EVs in Doxorubicin (DOX)-induced cardiomyocytes senescence remains elusive. In this study, we found that human serum EVs inhibited DOX-induced senescence in H9C2 cells, which was abolished by miR-34a mimic. Our study also proved that miR-34a mediated DOX-induced H9C2 cell senescence by targeting phosphatase 1 nuclear targeting subunit (PNUTS)...
November 29, 2018: Journal of Cardiovascular Translational Research
Fabiana Geraci, Paolo Ragonese, Maria Magdalena Barreca, Emanuele Aliotta, Maria Antonietta Mazzola, Sabrina Realmuto, Giulia Vazzoler, Giovanni Savettieri, Gabriella Sconzo, Giuseppe Salemi
This study was designed based on the hypothesis that changes in both the levels and surface marker expression of extracellular vesicles (EVs) isolated from the cerebrospinal fluid (CSF) may be associated with the clinical form, disease activity, and severity of multiple sclerosis (MS). The analyzes were performed on subjects affected by MS or other neurological disorders. EVs, which were isolated by ultracentrifugation of CSF samples, were characterized by flow cytometry. A panel of fluorescent antibodies was used to identify the EV origin: CD4, CCR3, CCR5, CD19, and CD200, as well as isolectin IB4...
2018: Frontiers in Cellular Neuroscience
Eleana Hatzidaki, Ioanna Vlachou, Aspasia Elka, Evanthia Georgiou, Maria Papadimitriou, Aggelos Iliopoulos, Ioannis Papasotiriou
In Research Genetic Cancer Center (RGCC), we are in the process of synthesizing a novel ERK inhibitor. We have currently synthesized an intermediate molecule, RGCC169, that needed to be tested to confirm we are using the appropriate synthetic pathways. Because of the limited solubility the compound exhibits, a strategy had to be devised for the free entrance of the molecule into the cell. Extracellular vesicles (EVs) were isolated by polyethylene glycol precipitation and identified by western blot and scanning electron microscopy...
November 26, 2018: Anti-cancer Drugs
Ssu-Han Wang, Gunn-Guang Liou, Szu-Heng Liu, Jeffrey S Chang, Jenn-Ren Hsiao, Yi-Chen Yen, Yu-Lin Chen, Wan-Ling Wu, Jang-Yang Chang, Ya-Wen Chen
Oral squamous cell carcinoma (OSCC) LN1-l cells previously showed greater capacities for lymphangiogenesis and lymph node metastasis compared to their parental OEC-M1 cells, in addition to an ability to enhance the migration and tube formation of lymphatic endothelial cells (LECs). Purified by a series of differential centrifugations and characterized using electron microscopy, dynamic light scattering, and western blot, LN1-1 cell-derived extracellular vesicles (LN1-1 EVs) were shown to promote LEC migration, tube formation, and uptake by LECs more effectively than did OEC-M1 cell-derived EVs (OEC-M1 EVs)...
November 28, 2018: International Journal of Cancer. Journal International du Cancer
Kentaro Jingushi, Motohide Uemura, Kosuke Nakano, Yujiro Hayashi, Cong Wang, Yu Ishizuya, Yoshiyuki Yamamoto, Takuji Hayashi, Toshiro Kinouchi, Kyosuke Matsuzaki, Taigo Kato, Atsunari Kawashima, Takeshi Ujike, Akira Nagahara, Kazutoshi Fujita, Koji Ueda, Kazutake Tsujikawa, Norio Nonomura
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, responsible for approximately 90‑95% of cases. We previously reported a novel method that enables direct extraction of extracellular vesicles (EVs) from surgically resected viable tissues, yielding what we term tissue‑exudative extracellular vesicles (Te‑EVs). Quantitative LC/MS analysis identified 3,871 proteins in Te‑EVs, among which leukocyte‑associated immunoglobulin‑like receptor 1 (LAIR1) was highly enriched in tumor Te‑EVs...
November 20, 2018: Oncology Reports
Janneke Boere, Jos Malda, Chris H A van de Lest, P René van Weeren, Marca H M Wauben
The use of extracellular vesicles (EVs) as a potential therapy is currently explored for different disease areas. When it comes to the treatment of joint diseases this approach is still in its infancy. As in joint diseases both inflammation and the associated articular tissue destruction are important factors, both the immune-suppressive and the regenerative properties of EVs are potentially advantageous characteristics for future therapy. There is, however, only limited knowledge on the basic features, such as numerical profile and function, of EVs in joint articular tissues in general and their linking medium, the synovial fluid, in particular...
2018: Frontiers in Immunology
Rosie M Martinez, Russ Hauser, Liming Liang, Abdallah Mansur, Michal Adir, Laura Dioni, Catherine Racowsky, Valentina Bollati, Andrea A Baccarelli, Ronit Machtinger
BACKGROUND: Phenols and phthalates are potential endocrine disrupting chemicals (EDCs) that are associated with adverse health outcomes. These EDCs dysregulate a number of biomolecules and pathways, including microRNAs. MicroRNAs can be carried in transport systems called extracellular vesicles (EVs) that are present in most biofluids. EVs in the follicular fluid, which fills the ovarian follicle and influences oocyte developmental competency, carry microRNAs (EV-miRNAs) that have been associated with In Vitro Fertilization (IVF) outcomes...
November 24, 2018: Environment International
Ramanathan Vaidyanathan, Ren Hao Soon, Pan Zhang, Kuan Jiang, Chwee Teck Lim
Technological advancements in research on circulating biomarkers from patient derived blood have enabled a less invasive means of diagnosing non-hematologic cancers. Considered a more practical way of real-time patient monitoring than traditional tumor biopsy, liquid biopsy markers including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) and exosomes certainly have the potential to change the dynamics of cancer management and treatment. Liquid biopsy essentially presents a snapshot of the disease from the primary and/or distant tumor locations and can be utilized for repeated sampling of tumor markers to adjust therapy according to the patient's response to treatment, also known as personalized or precision treatment...
November 27, 2018: Lab on a Chip
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