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ISEV 2017 Wraps Up in Toronto; Next Year Barcelona !

The final day of the highly successful International Society for Extracellular Vesicles (ISEV) 2017 Annual Meeting in Toronto, Canada, began with three simultaneous early-morning experts workshop sessions on “ExRNA Progress and Potential,” “EV Track,” and “Demonstration Workshop Analysis with FunRich.” The exRNA session was moderated by Louise Laurent, MD, PhD, from UC-San Diego, and included expert panel members, Aleksandar Milosavljevic, PhD, from Baylor College of Medicine, Kendall Jennsen, PhD, from TGen, and Jeffrey Franklin, PhD, from Vanderbilt University Medical Center. The sessions were designed to foster open interaction between the audience and the expert panelists, and Dr. Laurent framed the discussion by suggesting a focus on where we are now and what we need to make progress going forward. She noted that standardization is an ongoing effort with variability in methods, variability in reproducibility, and the existence of intrinsic, systematic biases in techniques that are reproducible. She indicated that standardization of collection, processing, and analytical methods is needed and standards that are developed need to be made available to the community. Dr. Milosavljevic remarked on the value of pipelines used by the exRNA Consortium and data sharing carried out through the exRNA Atlas (http://exrna-atlas.org/). Dr. Laurent mentioned the needs for single vesicle analysis and improved methods for vesicle enumeration and sizing. One audience member raised the question of methods to isolate exRNA from different body fluids and another contributed information on an effort undertaken in Australia to address some of the method standardization issues. He said that the Australian National Measurement Institute had asked 20 different labs to carry out size measurements and then analyzed the data to develop standard operating procedures. The last part of the session focused on the importance of understanding EV biology and efforts to determine the physiological relevance of exRNAs. Dr. Franklin noted that sometimes mixtures have the greatest activity and that perhaps function may actually require heterogeneity. The importance of assembling a reference list of miRNAs that do not change significantly in different body fluids was mentioned.

MORNING SYMPOSIA

The experts workshop sessions were followed by three simultaneous symposia on “EVs in Cardiovascular Disease and Vascular Disorders,” “EVs in Immune System and Inflammation,” and “Novel Developments in EV Biogenesis and Characterization.”

The first talk in the “EVs in Immune System and Inflammation” was given by Carole Parent of the National Cancer Institute and was titled “Exosomes As Key Regulators of Signal Relay During Chemotaxis.” Her group showed that LTB4, a key secondary chemoattractant in neutrophils, and its synthesizing enzymes, localize to intracellular MVBs that, upon stimulation, release their content as exosomes. The group’s findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. The group also investigated the mechanism by which LTB4 synthesizing enzymes, which are primarily localized on the nuclear envelope, are repackaged in exosomes and provide evidence that lipid homeostasis is involved in LTB4 vesicular packaging. The group believes that the packaging of chemoattractants in exosomes may provide a means of maintaining highly diffusible signals available for long-range cell-cell communication, and suggest that this newly revealed mechanism may be used by other signals to foster communication between cells in harsh extracellular environments.

The second talk was titled “Anti-Tumor Effect of Bacterial Outer Membrane Vesicles Mediated by Interferon-,” and was given by Hyun Tak Park of Postech in Korea. His group demonstrated that administration of bacterial EVs, especially gram-negative bacterial OMVs, resulted in a remarkable anti-tumor effect with no noticeable side effects. Moreover, it appeared that the anti-tumor effect of OMVs is mediated in an interferon (IFN)--dependent manner as IFN--deficient mice were not affected by OMV treatment. The group suggests that bacterial OMVs are promising immunotherapeutic agents to treat various cancers and could bring a new insight to the development of novel immunotherapies in the future.

The following talk was given by Niels H.H. Heegaard of Odense University Hospital in Copenhagen, and was titled “The Particular Pathology of Systemic Lupus Erythematosus.” He reported that deep proteome profiling of microparticles (MPs) from SLE patients and healthy controls (HC) confirm the presence of a subfraction of abnormal MPs in SLE. Furthermore, he said his group has characterized, for the first time, the extremely different proteome profile of Annexin V (AnxV)-non-binding MPs from SLE patients that seems to be responsible for the differences in the total MP profiles that are unique for SLE. He noted that the characterization of these MPs (luposomes) is important for understanding the pathogenesis of SLE, for the development of new diagnostic tools, and also provide venues for the development of new therapeutic concepts.

The final talk of the symposium was titled “Presence of Diabetes Autoantigens in EVs Derived from Human Islets,” and was given by Craig Hasilo of McGill University. His group showed that islet-conditioned medium (ICM) EVs, containing various levels of DAA, GAD65, ZnT8, and Glu2, were detected with a consistent size profile between non-diabetic donors. Proteomic evaluation reflected an islet-specific protein signature capable of promoting an immune response. The group believes that these biomarkers may be strong targets for early diagnostic markers of -cell injury and interventional strategies in diabetes and islet transplantation.

SECOND FEATURED ABSTRACT SESSION

The morning symposia were followed by the second featured abstract session that spotlighted the second set of three most highly rated abstracts.

The first was “Milk-Derived EVs from Non-Allergic and Allergic Mothers Differ in T Cell Modulatory Capacity and Have a Distinct Protein Composition,” presented by Martijn van Herwijnen of Utrecht University. The results showed that T cell proliferation, upregulation of activation markers, and overall cytokine production were inhibited in the presence of milk-derived EVs, in contrast to T cells that were cultured with milk supernatant depleted of EVs. Remarkably, according to the group, milk-derived EVs from allergic mothers inhibited T cell activation to a lesser extent that did EVs from non-allergic mothers. By comparing the proteomes of milk-derived EVs from allergic and non-allergic mothers, the scientists found quantitative differences in key proteins between these two groups. These individual proteins linked specifically to the Rac1 and CDC42 signaling pathways, affecting cell proliferation pathways. The scientists noted that this data shows that milk-derived EVs differ in their T cell modulatory capacity depending on the allergic status of the mother. The reduced T cell inhibition by EVs from allergic mothers might be due to the relative abundance of key proteins in these EVs.

The next honored abstract was “Characterizing Extracellular RNA Inside and Outside of Vesicles,” presented by Dmitry Ter-Ovanesyan of Harvard University. He found that the majority of RNA (particularly the small RNA fraction) in an exosome pellet isolated by differential centrifugation is not inside vesicles when comparing Bioanalyzer traces of the untreated pellet to the proteinase/RNase treated one. However, qRT-PCR and RNA-Seq analysis demonstrated that the mRNAs in the exosome pellet are inside the vesicles. The group believes that identifying RNAs that are truly inside vesicles has important implications for studying the role of exosome cargo in intercellular communication.

The third honored abstract was titled “Live Tracking of Endogenous Exosome Communication in Vivo,” and was presented by Frederik J. Verweij of the VU University Medical Center Cancer Center in Amsterdam. The group used a combination of light- and electron microscopy (LM and EM) to observe exosome release in vivo and track a massive pool of endogenous exosomes in the blood flow of zebrafish embryos. Site-specific expression confirmed that these exosomes originated from the Yolk Syncytial Layer (YSL), a multinucleate cell layer in between the yolk and the developing embryo with essential nutrient transport functions, sharing functional homologies with the mammalian placenta. The group concluded that its data could support a role for YSL-derived EVs in nutrient delivery during development, which is the lab’s current focus. The group believes that, altogether, its data reveals for the first time the release, journey, and target of endogenous exosomes in vivo. The group proposes the zebrafish as a new model to study endogenous EVs in vivo that will open new avenues to unravel fundamental aspects of EV biology.

CLINICAL & SCIENTIFIC WRAP-UPS

Next, International Organizing Committee Chairperson Sumitsa Sahoo, PhD, introduced Uta Erdbrugger, MD, and Eric Boilard, PhD, to provide brief clinical and scientific wrap-ups of the ISEV2017. In an alternating dual presentation, Dr. Erdbrugger first noted the trend of heterogeneity and the emphases on EV morphology and content. She thought that this year’s meeting showed a greater diversity of topics and diseases compared to previous meetings. Dr. Boilard remarked on the themes of moving from bulk to single vesicle analysis and from descriptive to mechanistic analysis. He also stressed the importance of studying subtypes of EVs and implementing more rigor in EV research.

Dr. Erdbrugger then noted recent advances in technology, including acoustic separation, microfluidics, chip technology, live imaging, high-res flow analysis, and the use of computer modeling. Dr. Boilard also emphasized the themes of biogenesis, addressability (zip codes), content, and function. Dr. Erdbrugger noted that EVs are ideal candidates for biomarkers, but that to advance these potential markers from bench to bedside, technology advances are needed to simplify and speed the means of identifying these biomarkers from patients.

The distinguished duo closed by stating that EV research is as diverse as the vesicles being studied, asserting that EV research is fun, and giving a warm thank-you to the highly interactive and enthusiastic audience for making ISEV2017 successful.

ISEV 2017 JUNIOR MEMBER SCHOLARSHIP AWARDS

Dr. Sahoo then stepped forward to announce and recognize the 25 Junior Member Scholarship winners for the ISEV 2017 annual meeting. The scholarships are intended to support young researchers (students and postdocs) in pursuing their studies in the area of EVs through attendance at the ISEV 2017 annual meeting. Among the 25 winners were junior ISEV members from Austria, Brazil, Germany, Canada, USA, The Netherlands, Ireland, Japan, China, Korea, UK, France, Australia, and Portugal. Among the winning abstracts were ones entitled “Molecular Subtypes of Glioma Stem Cells As Determinants of Tumor Vesiculome and Extracellular Vesicle Mediated Intercellular Communication,” “Real-Time Quantification of Multivesicular Body-Plasma Membrane Fusion Reveals Modulation of Exosome Release by G Protein-Coupled Receptor Signaling,” and “Picornavirus Infection Induces the Release of Distinct EV Populations Containing Infectious Virus and Altered Host-Derived Contents.” You may view the entire list of scholarship winners and their abstract titles at this link: http://isev.site-ym.com/page/ISEV2017_Scholarship.

ABSTRACT, POSTER, & ORAL PRESENTATION AWARDS

Next, the awards for the seven highest-scoring abstracts, from a total of 620 were announced. The winners were Dmitry Ter-Ovanesyan, Erik Abels, Fabvia Lucien, Frederik K. Verweij, Maartin Babelman, Martijn Hermijnen, and Shijing Yuu.

Next, the awards for outstanding posters, three for each day, were announced. The winners were Ashish Agrawal, Jose Bermudez, Tessa Seale, Gaesh Shelke, Naama Koifman, Vanessa Sanchez, Giorgio Bergamini, Nhung Thi Hong Dinh, and Vincent Yeung.

Then, the three awards for outstanding oral presentations, one for each day, were announced. These winners were Jan Van Deun, Sten Libregts, and Tomer Cooks.

THANKS TO ALL FROM DR. SAHOO AND PRESIDENT ANDY HILL

Dr. Sahoo then called the hard-working members of the ISEV International Organizing Committee to come to the stage to receive a token of great appreciation for their awesome work on ISEV2017, the largest ISEV meeting ever.

Then, ISEV president Andy Hill expressed his and everyone’s great thanks to Dr. Sahoo for the “tremendous” job she had done in leading the effort to organize this “best” ISEV meeting ever.

ON TO BARCELONA FOR ISEV 2018 !!

Marca Wauben, PhD, then stepped forward to first announce an upcoming workshop on EVs As Biomarkers of Disease in Birmingham, UK in December 2017 (http://www.isev.org/events/EventDetails.aspx?id=968703); and then to make the big announcement that the ISEV 2018 Annual Meeting would be held in Barcelona, Spain, May 2-6, 2018 (http://www.isev2018.org). The chairman of the 2018 International Organizing Committee will be Juan M. Falcon-Perez.

SAFE TRAVEL WISHES AND CLOSING HUMOR

Gregarious ISEV president Andy Hill then thanked Dr. Sahoo again for her superb efforts and wished the record 960 attendees safe travels home. He also thanked the meeting management team and the meeting sponsors for their great contributions. Before closing, he could not resist mentioning that he had tweeted out an EV joke request that started out “An exosome, a microvesicle, and an oncosome walk into a bar ... He then announced the three funniest fill-ins that he had received. Then, with a wide smile on his face, he bade the attendees a warm farewell and said he hoped to see all of them again next year in Barcelona!

MEETING SPONSORS

Sponsors of this year’s annual ISEV meeting included gold sponsor iZON Science Ltd; silver sponsors Malvern Instruments, Oxford Nanoimaging (ONI) Ltd, Particle Metrix Inc., Thermo Fisher Scientific, bronze sponsors AcouSort AB, Apogee Flow Systems Ltd, Beckman Coulter Life Sciences, Becton Dickinson, Cell Guidance Systems, Cosmo Bio Co Ltd, Evox Therapeutics Limited, Hansa Bio Med Life Sciences, Hitachi Chemical Diagnostics Inc, MBL International, Norgen Biotek Corp, Sysmex Corporation, System Biosciences (SBI), Wako Chemicals USA; Attendee Lanyard Sponsor Codiak BioSciences; and Education Day sponsor BioCytex. The ISEV also noted that Mount Sinai Heart is a Friend of the ISEV.

[ISEV 2018 Annual MeetinG] [ISEV 2017 Annual Meeting May 18-21]