Syndicate content

Archive - Oct 31, 2019

Date

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Final Day (Day 5), Thursday, October 10

Thursday was the last day of the 2019 ASEMV meeting and a number of interesting topics were presented. Two are reported on here. Louis Laurent, MD, PhD, of the University of California-San Diego (UCSD), spoke on the “Discovery and Verfication of Extracelular miRNA Biomarkers for Non-Invasive Prediction of Preeclampsia in Asymptomatic Women.” Dr. Laurent said that she and colleagues performed small RNA-seq of maternal serum exRNAs to discover and verify miRNAs differentially expressed in patients who later developed preeclammpsia. Serum collected from 73 preeclampsia cases and 139 controls between 17-28 weeks gestational age, divided into separate Discovery and Verification cohorts, was analyzed by small RNA seq. Discovery and verification of univariate and bivariate miRNA biomarkers revealed that bivariate biomarkers verified at a markedly higher rate than univariate markers. The majority of verified biomarkers contained miR-155-5p, which has been reported to mediate the preeclampsia-associated repression of eNOS by TNF-alpha. Deconvolution analysis revealed that several verified miRNA biomarkers came from the placenta and were likely carried by placenta-specific EVs. Norman Haughey, PhD, Johns Hopkins University School of Medicine, presented a talk entitled “Astrocyte-Derived EVs Shed in Response to IL-1 Promote Stabilization of APP Translation Through Ligand-Independent Activation of the Wnt Pathway in Neurons.” In his introduction, Dr. Haughey noted that chronic inflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD) by upregulating amyloidogenic processing of APP. Based on previous findings that inflammatory stimuli modify the cargo of astrocyte-derived EVs (ADEV), Dr.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 4, Wednesday, October 9

Wednesday’s sessions of the annual ASEMV 2019 meeting at Asilomar,in Pacific Grove, California, featured multiple exciting presentations. Among the 19 talks of the day, we will focus on five of particular interest. Luis Rodriguez-Borlado, PhD, of Capricor Therapeutics, delivered as presentation titled “Extracellular Vesicles from Cardiosphere-Derived Cells (CDCs) Are Taken Up by Muscle Stem Cells and Increase Exercise Capability in a Duchenne Muscular Dystrophy Model.” Dr. Rodriguez-Borlada introduced his discussion by stating that Duchenne muscular dystrophy (DMD) patients infused with CDCs showed an improvement in PUL (pullulanase) activity, skeletal muscle activity, and a reduction in myocardial scarring when compared to placebo-treated patients. He noted that there is wide acceptance that most of the therapeutic effects observed in cell therapies using non-engrafting cells are caused by paracrine factors secreted by the delivered cells. In the current work, Dr. Rodriguez-Borlado said his group observed significant improvement in exercise capability in mdx mice (DMD model mice) treated wit CDC-EVs when compared with control-treated mice. EVs from immortal CDCs also showed immunomodulatory capabilities on macrophages and improved exercise capability in mdx mice, opening the possibility of developing consistent, robust, and affordable manufacturing process for producing clinical-grade EVs. Julia Saugstad, PhD, Oregon Health & Science University, presented work by a collaborative group and the presentation was titled “Establishing the Contributions of Extracellular miRNAs to Alzheimer’s Disease.” As background, Dr. Saugstad said that Alzheimer’s disease (AD) is the most common form of dementia, the sixth leading cause of death in the United States, and fifth-leading cause of death in those age 65 and older.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 3, Tuesday October 8

Tuesday’s sessions of the annual ASEMV 2019 meeting at Asilomar, California, featured many exciting presentations. Among the 16 talks of the day, five were of particular interest. The first was by Ryan McNamara, PhD, of University of North Carolina-Chapel Hill, whose presentation was titled “EVs from Kaposi Sarcoma-Associated Herpes Lymphoma Induce Long-Term Endothelial Cell Reprogramming.” Dr. McNamara noted that extracellular communication is critical for organismal homeostasis, and thus presents as a major network for viruses to usurp for viral pathogenesis. EVs package contents from a donor cell to communicate with its surroundings, and evolutionarily diverse viruses have been shown to hijack this communication axis to promote pathogenesis. Previously, Dr. McNamara and colleagues had showd that the oncovirus Kaposi’s Sarcoma-Associated Herpes Virus (KSHV) incorporates viral miRNA into EVs secreted from infected cells during the “latency stage” of the viral life cycle. They hypothesized that these modified EVs, termed KSHV-EVs, aid in the establishment of a more favorable niche for disease/tumor progression. Their current results demonstrate that KSHV can modify the local environment using EVs. The group currently proposes that oncoviruses such as KSHV utilize the extracellular communications network through EVs to establish a niche favorable for disease progression and tissue transformation. This allows for the virus to reshape the local environment with minimal spread of the infectious agent, and without tripping immune alarms. In a following presentation, Jeffrey Savas, PhD, from Northwestern University, spoke on how “Viral Scission Factor Alix Tunes Neuronal Communication Through EVs.” Dr. Savas began by noting that synaptic plasticity is a dynamic process facilitating adaptable and flexible communication.

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.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles Opened Sunday Evening, October 6, at Asilomar in Pacific Grove, California

The 2019 annual meeting of the American Society for Exosomes and Microvesicles (ASEMV) was held October 6-10 at the gorgeous Asilomar Conference Grounds in Pacific Grove, California, home of migrating monarch butterflies, steps from the Pacific Ocean, and just 120 miles south of San Francisco. The glorious natural setting was almost matched perhaps by the broad range of 60 scintillating presentations delivered by scientists from around the country and world, during the five intense days of meetings focused on one of the most exciting aspects of biology and mediicine. This year’s meeting, organized as always by Stephen Gould, PhD, of Johns Hopkins, began on Sunday evening with a brief introduction on the history of the ASEMV annual meetings by Michael Graner, PhD, University of Colorado-Denver, and this was followed by the keynote presentation, sponsored by Caris Life Sciences, and delivered by Dr. Travis Thomson of the University of Massachusetts (Worcester, MA). Dr. Thomson’s address was titled “Arc and Copia in Exosome-Mediated Information Exchange.” Dr. Thomson described Arc as a “master regulator of neuronal plasticity and as a remnant of a transposon gag region of a virus. In a 2018 article in Cell (https://www.ncbi.nlm.nih.gov/pubmed/29328915), Dr. Thomson and colleagues noted that Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. In the Cell article, Dr.