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SELECTBIO Conferences Extracellular Vesicle-based Dx & Rx Summit

Extracellular Vesicle-based Dx & Rx Summit Agenda



Co-Located Conference Agendas

Circulating Biomarkers World Congress 2019 | Liquid Biopsies 2019 | Extracellular Vesicle-based Dx & Rx Summit | Flow Cytometry 2019: Biomarkers & Diagnostics | 

Print Agenda

Thursday, 28 March 2019

10:45

Lucia LanguinoConference Chair

Conference Chaiperson Opening Remarks
Lucia Languino, Professor of Cancer Biology, Thomas Jefferson University, United States of America


Summit Session Title: Emerging Themes in EV-based Diagnostics and Therapeutics

11:00

Jan LötvallKeynote Presentation

Diversity of Extracellular Vesicles to Understand their Diagnostic and Therapeutic Potential
Jan Lötvall, Professor, University of Gothenburg; Founding President of ISEV, Sweden

This presentation will discuss the diversity of extracellular vesicles, primarily from a clinical perspective. Specifically, the presentation will show the presence of extracellular vesicles in tissues, specifically healthy tissues as well as different types of tumors.  Data showing the presence of multiple types of EVs in different types of tissues will be presented, as well as the opportunities of utilizing that knowledge for clinical use.

11:30

Hollis ClineKeynote Presentation

Exosome Signaling in Brain Development
Hollis Cline, Chair of Neuroscience and Hahn Professor of Neuroscience, The Scripps Research Institute, United States of America

Exosomes are thought to be secreted by all cells in the body and could to be involved in intercellular communication. I will describe experiments in which we tested whether neural exosomes regulate the development of neural circuits and whether exosome-mediated signaling may be aberrant in in vitro models of a neurodevelopmental disorder using human induced pluripotent stem cells (hiPSC) and in vivo rodent models. I will describe results of quantitative proteomic analysis of exosomes. Together our studies indicate that exosomes have the capacity to influence neuron and circuit development.

12:00

Networking Lunch in the Exhibit Hall and Poster Viewing

12:30

Dominique PV de KleijnKeynote Presentation

Plasma Extracellular Vesicles Sub-fractions For Diagnosis of Cardiovascular Disease
Dominique PV de Kleijn, Professor Experimental Vascular Surgery, Professor Netherlands Heart Institute, University Medical Center Utrecht, The Netherlands, Netherlands

Cardiovascular Disease (CVD) is with the cardiovascular events of Ischemic Heart Disease and Stroke, the number 1 and 2 cause of death in the world and expect to increase especially in Asia.

Ischemic heart disease (IHD) comprises 3 entities: stable coronary artery disease (SCAD), unstable angina (UA) and myocardial infarction (MI). Because IHD is associated with an increased risk of adverse clinical events such as heart failure and death, early recognition of IHD is of utmost importance.

However, to diagnosis IHD is challenging, as many patients present with atypical symptoms. It is known that women have a different symptom sensation than men. Troponins are the main diagnostic tool for detection of MI. Blood biomarkers for SCAD (typically causing stable angina) and UA, however, are not available. These diagnoses frequently require hospital visits/admissions for time-consuming and costly (non)invasive tests.

We use a protein signature measured  in 3 different subsets of plasma extracellular vesicle as an accurate source for early diagnosis of SCAD and UA. Diagnosis of ischemic heart disease as well as reproducibility and simplification for microfluidics will be discussed.

13:00

Ymir GenomicsEV Isolation from Biofluids
Shannon Pendergrast, Chief Scientific Officer, Ymir Genomics

We will present several novel products and methods for the rapid and effective isolation of biofluid extracellular vesicles (EVs).

13:30

Chulhee ChoiKeynote Presentation

Exosome Engineering for Delivery of Cytosolic Proteins: Principles and Therapeutic Applications
Chulhee Choi, Professor and Chair, BioMedical Imaging Center, Korea Advanced Institute of Science and Technology (KAIST), President, Cellex Life Sciences, Korea South

Our group has recently developed an opto-genetically engineered exosome system, named ‘exosomes for protein loading via optically reversible protein–protein interaction” (EXPLOR) that can deliver soluble proteins into the cytosol of target cells via controlled, reversible protein–protein interactions (PPI). By integrating a reversible PPI module controlled by specific wavelength of light with the endogenous process of exosome biogenesis, cargo proteins of our interest can be loaded into newly generated exosomes. Protein-loaded exosomes were shown to significantly increase intracellular levels of cargo proteins and their function in recipient cells in both a time- and dose-dependent manner. In this presentation, I will introduce the basic principles of EXPLOR technology and follow-up studies for therapeutic applications including sepsis.

14:00

Induced Tissue Regeneration (iTR) Using Extracellular Vesicles
Dana Larocca, VP Discovery Research, AgeX Therapeutics, United States of America

There is a critical unmet medical need for new therapies to treat age-related diseases given the increasing burden of a global demographic shift toward older populations.  Extracellular vesicles (EVs) have been demonstrated to be largely responsible for the regenerative effects of stem cells in a variety of animal models of age-associated diseases including cardiovascular diseases.  We hypothesize that EVs made by cells from early human development will convey strong regenerative signals because this is when regenerative capacity is at its peak. We used partial differentiation of human pluripotent stem cells to derive a large library of highly scalable and clonally pure embryonic progenitor cell lines.  Over 200 progenitor lines were originally established to meet the high demands of cell purity and scalability needed to treat a large aging population.  We are now mining this diverse library of cell lines for their ability to provide a scalable source of highly regenerative EVs.  We found that embryonic progenitor derived EVs had higher angiogenic activity than adult stem cell derived EVs. Moreover, angiogenic activity was maintained by EVs produced by cells at up to at least 52 population doublings and following bioreactor scale-up.  We are currently mapping bioactivity and cargo of EVs derived from a variety of embryonic cell types including endothelial, pericyte, smooth muscle, osteochondral and brown adipocyte progenitors.  We anticipate that the resulting library of diverse embryonic EVs will be a valuable resource for developing EV therapies for cardiovascular and other age-related diseases.

14:30

Adipose-derived Stem Cell Extracellular Vesicles can be Specifically Tuned for Soft Tissue Repair and Wound Healing
John Ludlow, Executive Director, Regenerative Medicine, Zen-Bio, Inc., United States of America

Our research program is designed to provide critical proof-of-concept data demonstrating manufacturing conditions and wound healing properties of stem cell-derived extracellular vesicles.

15:00

The HSP-Accessorized Exosome: Presence in States of Danger, Disease, and Disruption
Michael Graner, Associate Professor, Dept of Neurosurgery, University of Colorado Anschutz School of Medicine, United States of America

Heat shock proteins (HSPs) function as chaperones under both normal and pathologic conditions. As chaperones they assist in protein folding, in holding protein complexes for current or future activation, and in the degradation of senescent proteins for recycling of components and display for immune surveillance. During stressful situations, HSP quantities and/or activities are increased as cells and tissues seek protection from insults. On occasion, these insults can result in the cell surface display of HSPs, which can then lead to the surface display of HSPs on exosomes, membrane-enclosed vesicles released extracellularly after passage thru the endosomal system. HSPs present on the cell surface or in the extracellular space are regarded as “danger signals” in an ancient biologic paradigm. HSP-accessorized exosomes may act as “danger boli”, carrying not only the HSPs, but hundreds of components of the stressed parental cell, capable of prompting immune responses, or possibly immune suppression, depending on the status of the recipient cell. Here we show that exosomes from the blood of patients suffering from neurologic maladies (cancer, brain injury, multiple sclerosis) are precipitated by peptides designed to bind HSPs. The metabolome of such exosomes is distinct from that of blood exosomes from healthy donors. Such HSP-accessorized exosomes possess inflammatory properties and may serve as biomarkers in a “liquid biopsy” setting.

15:30

Human Liver Stem Cell-derived Nano-EVs – A Broad Platform Technology for Cancer and Regeneration
Daniel Gau, Head of Business Development, Unicyte AG, Germany

Extracellular vesicles and exosomes (EVs), and in particular when derived from stem cells are emerging as a new therapeutic modality in regenerative medicine. Stem cell derived EVs are of high abundance, are not self-replicating, are not immunogenic, own a tissue specific targeting capability and thus address hurdles of stem cells for translation into indications with large patient impact. With more than 10 years research in the field, Unicyte has developed a strong therapeutic pipeline in fibrotic disorders and oncology, using it’s proprietary Human Liver Stem Cell and derived nano-EVs (HLSC-nEVs). With their natural targeting capability to liver tissue and to tumor cells, HLSC-nEVs have been investigated in Hepatocellular carcinoma (HCC) the most common cause of death in people with cirrhosis. In pre-clinical studies, HLSC-nEVs decrease the growth and survival rates of tumor liver cells, while at the same time protecting normal hepatocytes. In addition, HLSC-nEVs have demonstrated strong liver regeneration capabilities in various models of acute and chronic liver injury, ex-vivo scaffold re-cellularization and more recently on normothermic transplantation models. These results suggest that HLSC-nEV address the underlying liver disease and inhibit tumor growth in hepato-cellular carcinoma via a multi-factorial mechanism of action. Unicyte is currently preparing clinical transition of its HLSC-nEVs programs in various indications.

16:00

Cell-to-Cell Propagation of Pathogenic Aberrant Dipeptide Repeat Proteins in C9orf72-Linked Amyotrophic Lateral Sclerosis
Davide Trotti, Professor, Scientific Director, Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, United States of America

Nucleotide repeat expansions (NREs) are prevalent mutations in a multitude of neurodegenerative diseases. Abnormal translation of these repeat regions produces proteins that contribute to the pathogenesis of these diseases. However, the mechanisms and drivers of the aberrant translation are not well understood. Here we analyzed whether different cellular stressors promote these aberrant translations of peptides associated with the G4C2 hexanucleotide expansions in C9orf72, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that activating glutamate receptors or increasing neuronal activity trigger these aberrant translation of  neurotoxic peptides. In addition, we postulate that cell-to-cell transmission of these disease-linked aberrant peptides could be a modality by which toxic insults spread in disease-afflicted CNS areas in ALS and FTD. We are presenting evidence here using in vitro and in vivo approaches that indeed transmission of these aberrantly translated peptides occurs via exosomes and that transfer of injury could happen from the neuron of peptide formation to neighboring neurons but also to neurons connected in neuronal networks.

16:30

NanoView BiosciencesRoutine Single EV Protein Biomarker Analysis
Clayton Deighan, Regional Sales Director, NanoView Biosciences

One of the major limitations to the realization of the potential in EV biomarkers is the lack of techniques for phenotyping individual EVs. In this presentation we will present the ExoView platform, a new tool for the capture and characterization of EVs from many sources. By coupling a validatable immunoassay for capturing EVs with no prior purification with a sensitive interferometric measurement of single EVs (50+nm) with no additional labeling we separate important populations from the noise.  The secondary analysis by counterstaining for biomarkers of interest can be custom designed by the user allowing for detection of the markers of interest in their research with minimal assay development time.  Example datasets for marker colocalization will be presented for EVs from a variety of sources.

17:00

ReNeuronAn Exosome-based Drug Delivery Platform Derived From an Immortalized Human Neural Stem Cell (hNSC) Line
Randolph Corteling, Head of Research, ReNeuron

To ensure the scale required for clinical research and commercialization producer cell immortalization and clonal isolation is a practical strategy to produce consistent, functionally bioactive exosomes for use as therapeutic agents. Immortalization ensures production stability and reduces the need for equivalence testing.

CTX0E03 is a conditionally immortalized human neural stem cell line which has been manufactured to clinical-grade (GMP) standards using a 3-tier banking strategy and is currently in Phase II clinical evaluation for disability after stroke. Using the conditioned media produced during GMP manufacture, we have shown that CTX0E03 is an abundant producer of exosomes which can be readily isolated and purified at scale.

The CTX cell line can also be rapidly and efficiently modified to direct the expression of a variety of cargoes within the secreted EV population, whilst maintaining the key immortalized stem cell characteristics of the parental cell line.  The natural tissue tropism of CTX-derived exosomes can then be exploited to deliver loaded cargoes to target cells.

17:30

Extracellular Vesicles Go Nuclear
Aurelio Lorico, Professor of Pathology, Touro University Nevada, United States of America

Molecular mechanisms regulating EV biogenesis, their release, and subsequent uptake by target cells have emerged during the last two decades. How their cargo molecules are selectively delivered to their intracellular sites of action, including the intra-nuclear compartment, is still obscure. This issue is particularly important given that the biogenesis and functionality of EVs are dysregulated under pathological conditions. Recently, we described a novel sub-nuclear compartment which is created by the entry of small GTPase Rab7-containing late endosomes in the nucleoplasmic reticulum. The latter is shaped by superficial and deep nuclear envelope invaginations (NEI) penetrating into the nucleoplasm. Given that late endosomes in NEI has often an elongated appearance and resembles a sword in its scabbard, we proposed to name this dual-structure “spathasome” from Greek/Latin words “spathi/spatha” for sword. This structure appears to act as an intermediate compartment for the delivery of the content of endocytosed EVs (e.g., CD9/CD133 protein complexes and RNA molecules) to the nucleoplasm of their host cell. The NEI-associated late endosomes and nuclear localization of EV-derived proteins were observed in cancer cells and mesenchymal stromal cells in cultures and in breast cancer patient biopsies. A molecular complex, investigated by indirect immunofluorescence, fluorescence resonance energy transfer, immunoisolation techniques and RNA interference, was found to be responsible for the entry of EV cargo into the nucleoplasmic reticulum.

18:00

Industry Panel Discussion Focusing on Circulating Biomarkers & Liquid Biopsy


Add to Calendar ▼2019-03-28 00:00:002019-03-28 00:00:00Europe/LondonExtracellular Vesicle-based Dx and Rx SummitExtracellular Vesicle-based Dx and Rx Summit in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com