Exosomes and Microvesicles
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Friday, September 21
7:30-8:15 am Morning Coffee or Sponsored Breakfast Presentation (Opportunity Available)
Contact Ilana Quigley at email@example.com or 781-972-5457
8:30-8:35 Chairperson’s Opening Remarks
8:35-9:00 Novel Connections between Rho GTPases and Microvesicles in Cancer Progression
Richard A. Cerione, Ph.D., Professor, Molecular Medicine, Cornell University
The roles of microvesicles (MVs) in cancer are receiving a great deal of attention. MV cargo includes receptor tyrosine kinases, cytosolic and nuclear signaling proteins, and RNA transcripts which when transferred to recipient cancer cells, accentuates their transformed properties. Recently, we discovered that MVs isolated from highly aggressive cancer cells confer upon fibroblasts the characteristics of transformed cells. Moreover, we found that different Rho GTPases play important and distinct roles in MV formation and shedding, and that signaling to the metabolic machinery of cancer cells is required for MV biogenesis. These findings shed new light on the potential importance of MVs, as well as Rho GTPases, to cancer progression.
9:00-9:25 Oncogenic Extracellular Vesicles — Biological Effectors and Cancer Biomarkers
Janusz Rak, M.D., Ph.D., Professor, Pediatrics, Montreal Children’s Hospital Research Institute, McGill University
Intercellular trafficking of membrane-derived extracellular vesicles (EVs) represents an intriguing mode of intercellular communication. These processes are altered in cancer, where oncogenic pathways influence the properties and abundance of shed EVs. Notably, EVs mediate extracellular release of mutant proteins and nucleic acids causative for malignant transformation, such as oncogenes and tumor suppressors. Such oncogenic EVs (oncosomes) are taken up by various cells and may trigger transformation-like changes including altered growth, survival angiogenic phenotype, procoagulant conversion, and tumorigenesis. EVs circulating in blood offer unprecedented new access to driver mutations, molecular subtypes, drug targets and other actionable information in cancer.
9:25-9:50 Extracellular Vesicles in Leukemia — Biology and Biomarker Opportunities
Peter Kurre, M.D., Associate Professor, Pediatrics, Oregon Stem Cell Center, Department of Pediatrics and Cell & Developmental Biology, Oregon Health & Science University
Extracellular vesicle trafficking is a constitutive cellular function important to cell-cell communication. Studies confirm that leukemia cells release vesicles rich in protein and RNA cargo. Acute- and chronic myelogenous leukemia vesicles are rich in established biomarkers, including BCR-ABL and Flt3-ITD, respectively, and contain abundant microRNA. Vesicle trafficking promotes proliferative and proangiogenic effects in co-cultured stromal cells. Broadly, extracellular vesicle cargo emerges as a powerful regulator of cell fate in the microenvironment. We propose a mechanistic role for vesicles during leukemogenesis and significant potential for biomarker discovery.
9:50-10:15 The Biology and Clinical Potential of Tumor-Derived Microvesicles
Crislyn D’Souza-Schorey, Ph.D., Professor, Biological Sciences, University of Notre Dame
10:15-11:15 Coffee Break in the Exhibit Hall with Poster Viewing
11:15-11:20 Chairperson’s Opening Remarks
11:20-11:45 An Emerging Role of Microvesicles and Exosomes in Regenerative Medicine
Janina Ratajczak, M.D., Ph.D., Assistant Professor, Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville
Stem cells are a rich source of microvesicles (exosomes) released from their surface or endosomal compartment that may deliver proteins, RNA and miRNA into damaged organs. Based on this, paracrine effects probably make major contributions in most of the currently reported positive results in clinical trials employing adult stem cells. It will be discussed how these paracrine mechanisms could be exploited in regenerative medicine to achieve better therapeutic outcomes. This approach may yield critical improvements in current cell therapies before true pluripotent stem cells isolated in sufficient quantities from adult tissues and successfully expanded ex vivo will be employed in the clinic.
11:45 am-12:10 pm Developing Exosomes for Therapy
Sai Kiang Lim, Ph.D., Principal Investigator, Institute of Medical Biology, A-Star, Singapore; Research Associate Professor, Surgery, Yong Loo Lin School of Medicine, National University of Singapore
Exosomes are small lipid membrane vesicles that are secreted by many cell types. They carry both proteins and RNA, and could deliver this cargo into other cell types to elicit biological responses specific to the cargo content. Therefore, exosomes are biological intercellular delivery vehicles that would be ideal for therapeutic supplementation of proteins or RNAs depleted in a disease process or the delivery of proteins/RNA to delay or ameliorate a disease process. My group has demonstrated that exosomes secreted by mesenchymal stem cells exert a cardioprotective effect through the replacement of depleted proteins and supplementation of enzymes to activate survival signalling.
12:10-12:35 Exosomes: Novel Therapeutics for Treating Autoimmune Diseases
Paul D. Robbins, Ph.D., Professor, Metabolism and Aging, The Scripps Research Institute
Dendritic cells (DC) are professional antigen presenting cells able to stimulate or suppress the immune response. Bone marrow-derived, myeloid DC (BMDC) can reduce antigen-specific inflammation associated with a murine footpad model of delayed-type hypersensitivity (DTH) and reverse established murine collagen induced arthritis (CIA) following a single systemic administration. Exosomes from DC also are able to regulate the immune response in an antigen-dependent manner. In fact, the exosomes derived from immunosuppressive DC are always as or more effective than the parental DC in suppressing inflammation or autoimmunity. Thus, DC-derived exosomes represent an effective therapeutic approach for treating arthritis.
12:35-1:00 Refreshment Break
1:00-1:25 Exosomes Are Endogenous Nanoparticles that Can Deliver Biological Information between Cells
Huang-Ge Zhang, M.D., D.V.M., Ph.D., Professor, Microbiology and Immunology, University of Louisville
Exosomal particular size of 30-100 nm matches the size criterion for nanoparticles and opens up the possibility of using exosomes as a nanoparticle drug carrier. More importantly, exosomes released from different types of host cells have different biological effects and targeting specificities. Therefore, depending on the therapeutic goal, different types of exosomes can be combined with specific drugs and serve as carriers so that personalized medicine needs are met. In addition, exosomes do not appear to have cytotoxicity. Based on the perceived advantages of exosomes, they may well serve as a next-generation drug delivery mechanism that combines nanoparticle size with a non-cytotoxic effect, target specificity, and a high drug carrying capacity.
1:25-1:50 Delivery of Antigen-Specific Therapeutic Exosomes via Selected Surface Antibody and Containing dsRNA of Choice
Philip Askenase, M.D., Professor, Immunology, Yale University School of Medicine
We have discovered a new form of T cell regulation. Suppressive T cells from antigen tolerized mice release nano-vesicle exosomes that can be transfected with chosen miRNA to target and then suppress distant effector T cells by delivering the inhibitory miRNA. The suppressive miRNA exosomes act Ag-specifically via a coating of Ag-specific immunoglobulin free light chains that also can be altered by choice. These studies are relevant to a variety of diseases. This is the first example of T cell regulation via inhibitory miRNA passing from cell to cell via exosomes and acting Ag-specificity in vivo in an endocrine manner. It is relevant to current efforts to deliver siRNA in vivo, and promises to do so physiologically and antigen-specifically.
1:50-2:15 Vesicles in the Blood Stream: Interaction with Activated Endothelium
Raymond M. Schiffelers, Ph.D., Associate Professor, Laboratory Clinical Chemistry and Hematology, University Medical Center Utrecht
Extracellular vesicles in the blood stream are derived from a variety of cells. The most abundant appear to be derived from platelets and erythrocytes. Because of their size of approximately 100 nm, there are a limited number of cell types with which they can interact. In our experiments we recover the majority of isolated and reinjected vesicles within the macrophages in liver and spleen. At the same time, when endothelial cells cells become activated, we observe accumulation in the vessel wall, which appears to be dependent on alpha v- integrins. This has implications for diagnostic purposes and drug delivery strategies.
2:15 Close of Conference
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