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Exosome Education Blooms in Washington, DC

The 2015 Annual Meeting of the International Society for Extracellular Vesicles (ISEV) (http://www.isevmeeting.org/), with a special focus on exosomes, is being held this year in Washington, D.C., and will run from Thursday, April 23, through Sunday, April 26. The official meeting will be kicked off with plenary session addresses by NIH Director Francis Collins, M.D., Ph.D., and 2013 Nobel Laureate James Rothman, Ph.D., on Thursday morning. But before the official opening, the ISEV typically holds an Education Day, particularly for graduate students and those relatively new to the field, in order to bring them up to date on the history and also the latest developments in this fascinating fast-moving-field with so many major implications for clinical and myriad other biological applications. This year’s Education Day was organized jointly by Dr. Ken Witwer for the ISEV and Dr. Christopher Austen, Director of the NIH National Center for Advancing Translational Sciences, and was co-hosted by the ISEV and the NIH Extracellular RNA Communication Consortium (ERCC). The event was a huge success with approximately 400-500 attendees from all over the world completely filling the amphitheater for the entire day to hear many of the major leaders in this exploding field describing exosome history, recent advances, and also critical needs for increased standardization in work done to isolate and characterize exosomes. Included among the many fascinating talks was one by Dr. Yong Song Gho, from Pohang University in South Korea, a world leader on the cargo loading of vesicles, who spoke on the potential role of extracellular RNA (exRNA) in extracellular vesicle (EV)-mediated intercellular communication networks. He also mentioned that exosomes might have first been described in a cancer study in 1967, long before the term “exosome” had even been coined and one of the earliest dates ever provided for the much-debated “discovery” of exosomes. Dr. Michiel Pegtel of Utrecht University described his group’s work to associate biological function with the transfer of EV-RNA. He initiaily described work with Epstein-Barr virus (EBV) that actually codes for 44 non-human microRNAs. He set up an experiment to see if exosomes secreted by EBV-infected cells would transfer EBV-specific miRNA to uninfected cells, and indeed they did. He noted, however, that the functionality of miRNA transferred via exosomes remains to be rigorously demonstrated.

The closing talk, by Dr. Muller Fabbri of Children’s Hospital Los Angeles was titled “Exosomal miRNAs Orchestrate the Biology of the Tumor Microenvironment,” and began with a comparison of exosomes to hormones in that both circulate and bind to target cells. Dr. Fabbri described a system in which he looked at neuroblastoma in its microenvironment, and particularly on interactions between the tumor cells and neighboring macrophages. He showed first that the neuroblastoma produced exosomes whose cargo included miR-21 and miR-29a. He then showed the exosomes were secreted and entered nearby macrophages where the cargo was release and both miRNAs bound to toll-like receptor 8 (TLR8) in the endosomes of the macrophages. This ultimatele led to an increase in interleukin-6, which fed back to stimulate further neuroblastoma growth.

Earlier in the day, Dr. Todd Lowe, of the University of California-Santa Cruz, gave a very exciting talk on the variety of possible function of transfer RNAs that may have been overlooked for some time. The title of his talk was ”Profiling Overlooked Small Non-Coding RNAs derived from tRNAs Using ARM-Seq.” He emphasized that much is unknown about the processing and transport of tRNAs. He further noted that many tRNAs, of which there are ~500 in the human genome, undergo various modification and little is known about these modifications or their effects. Dr. Lowe suggested that tRNAs likely have many currently unknown roles that deserve exploration.

Dr. Clothilde Thery from the Institut Curie echoed an oft-repeated theme of the day as she emphasized the urgent need for reevaluating many of the methods and procedures of isolating and describing exosomes and other extracellular vesicles, particularly as recent work has disproved certain long-believed verities of exosome analysis, with one example being the idea that they bear distinguishing antigens on their surface. Many of these antigens have now been shown to not be specific for exosomes. Dr. Thery also noted that the types of RNA carried in exosomes need to be reexamined and reevaluated.

Dr. Stephen Gould of Johns Hopkins spoke just before Dr. Thery and he very interestingly highlighted the similarity between retrovirus budding and exosome biogenesis, He suggested that there might be much to be gained by pursuing this possible connection between exosomes and retroviruses, both for exosome researchers, as well as for virologists.

Many of the talks in the morning and early afternoon focused on different aspects of trying to improve the precision, quality control, standardization, reference standards, and other measures that are urgently need to improve the rigor of exosome studies and to advance this incredibly important and promising field as soon as possible.

Additional speakers during the day included Dr. Louise Laurent of UC-San Diego, Dr. Edit Buzras of Semmelweis University, Dr. Kendall Jensen of TGen, Dr. Yuana Yuana of the University of Amsterdam, Dr. An Hendrix of Ghent University Hospital, Dr. Muneesh Tewari of the University of Michigan, Dr. David Galas of the Pacific Northwest Diabetes Research Institute, Dr. P. Scott Pine of the National Institute of Standards and Technology, Dr. Esther Nolte ‘t Hoen of Utrecht University, Dr. Anna Krichevsky of Harvard University, Dr. Klaas Max of Rockefeller University, Dr. Aleks Milosavljevic of Balor College of Medicine, Dr. Joel Rozowsky of Yale University, Dr. Roger Alexander of the Pacific Northwest Diabetes Research Institute, Dr. Andy Hill of La Trobe University in Australia, Dr. Kirsty Danielson of Harvard University, Dr. Maria Giraldez of the University of Michigan, and Dr. Marca Wauben of Utrecht University.

At the close of the Education Day, Dr. Jan Lotvall, President of the ISEV, summarized the day’s various and exciting discussions, and hailed the audience for its endurance and enthusiasm about this stimulating new area of science. Dr. Lotvall also foreshadowed Thursday’s big talks that will be coming from Francis Collins and James Rotham.

It was a fabulous day and it will only get better as the official meeting gets underway tomorrow with an expected 750 scientists from around the world in attendance.

by Mike O'Neill, MA, and Ron Faanes, Ph.D.