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ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 2, Monday October 7

Monday’s sessions of the annual ASEMV 2019 meeting at Asilomar, in Pacific Grove, California, featured many exciting presentations. Among the 16 talks of the day, five were of particular interest. The first, “Methamphetamine Use Disorder Alters Plasma EV MicroRNA Expression,” was presented by Ursula Sandau, PhD, of Oregon Health & Science University (OHSU) in Portland, Oregon. Dr. Sandau noted that methamphetamine has deleterious effects to both peripheral organs and the central nervous system. The rewarding properties and addictive potential of methamphetamine are correlated with increased synaptic dopamine availability following alterations in dopamine and vesicular monamine transporter function. She reported results demonstrating that EV miRNA expression in subjects with methamphetamine use disorder was significantly different than in control participants, suggesting that methamphetamine may affect EV communication among cells. Dr. Sandau further noted that the differential miRNA expression also implicates a role for EVs in behavioral and physiological effects specific to methamphetamine and suggests that there may be changes in expression of miRNAs that are relevant to specific drugs of addiction, as well as to a spectrum of drug-mediated addiction disorders. In another compelling presentation, Franklin Monzon, PhD, of Spectradyne Particle Analysis (https://nanoparticleanalyzer.com/), spoke on “The Importance of Orthogonal Techniques in Quantifying Extracellular Vesicles.” Dr. Monson noted that, as EV research matures, so must the relevant measurement technologies. He reported on two simple experiments that he believes expose a critical failure of Nanoparticle Tracking Analysis (NTA) for quantifying EVs, with the small size of limit of detection of NTA depending strongly on the composition of the sample, causing 10,000-fold errors within the EV size range, relative to microfluidic resistive pulse sensing (MRPS) and transmission electron microscopy (TEM). He emphasized that results show that the use of orthogonal methods for EV quantification is critical. He noted that a researcher could be led severely astray by relying on NTA results in isolation, without an orthogonal technique for reference.

ALS BIOMARKERS IN NEURAL-DERIVED EXOSOMES

A third exciting presentation was given by Sandra Banack, PhD, of the Brain Chemistry Labs, Institute for Ethnomedicine (https://brainchemistrylabs.org/), in Jackson, Wyoming. Dr. Banack talk was titled “Searching for ALS Biomarkers in Neural-Derived Exosomes.” As an introduction, Dr.Banack noted that exosomes derived from blood plasma carry a unique source of information about biological processes. She said that the inherent stability of exosomes and their ability to cross the blood-brain barrier make them a potentially rich, in-vivo source of information about the brain. Her group is using neural-derived exoxomes (NDEs) to probe their miRNA cargo to search for biomarkers of amyotrophic lateral sclerosis (ALS). Dr. Banack described work in which high-quality miRNA was extracted from neural-derived exosomes (NDEs) that were enriched from blood plasma of ALS patients and controls. Next-generation sequencing (NGS) analysis identified 101 miRNAs of interest in neurological disease and qPCR validated 13 miRNAs that successfully separated controls from ALS patients using principal component analysis (PCA). Three miRNAs were down-regulated in ALS patients and ten were up-regulated. Of particular interest, Dr. Banack noted, are the linked miRNA pathways that relate to acetylcholine regulation, inhibition of apoptosis, and prevention of cartilage degeneration. Furthermore, she noted, some of these miRNAs have been reported as being related to other neurological diseases, such as Parkinson’s, Huntington’s, and Alzheimer’s diseases.

EXOSOMES & OSTEOARTHRITIS

A fourth important presentation was delivered by Malwina Czarny-Ratajcak, PhD, of the Tulane School of Mecine, and entitled “Exosomes from Synovial Fluid Facilitate Transport of Osteoarthritis Biomarkers and Proteins Inducing Cartilage Degeneration.” Dr. Czarny-Ratajcak said that the objective of her group’s work was to determine if the protein cargo of exosomes obtained from synovial fluid of patients with osteoarthritis contains molecules that contribute to initiation and development of this disease, and if this cargo is disease-specific. The group’s analysis included a comparison of osteoarthritis (OA) exosomes with exosomes isolated from patients with rheumatoid arthritis (RA), which has a different etiology than OA. According to Dr. Czarny-Ratajcak, the results indicated that the protein cargo of exosomes from synovial fluid is a source of disease-specific markers. Proteomics data from OA patients also showed proteins involved in activation of latent MMP9 and TGF-, which are key molecules in OA pathogenesis.

EVs FROM LACTOBACILLI PROTECTIVE AGAINST HIV

Monday’s sessions ended with thought-provoking presentation by Christophe Vanpoille, PhD, of NIH on “Extracellular Vesicles Released by Commensal Lactobacillus Suppress HIV-1 Infection.” Dr. Vanpoille noted that it has previously been shown that lactobacilli of various strains inhibit HIV-1 replication in human cervico-vaginal and tonsillar tissues ex vivo. Here, Dr. Vanpoille described the work of his group and collaborators to investigate whether the protective anti-HIV effect of lactobacilli is mediated by EVs released by these bacteria. The findings showed that the protective effect of Lactobacillus against HIV transmission is, in part, mediated by EVs released by these commensal bacteria. Dr. Vanpoille noted that these findings may lead to new strategies to prevent male-to-female sexual HIV transmission.