Hello. I am Carolina Soekmadji from Australia. I am currently an Adjunct board member and a member of the educational team of International Society for Extracellular Vesicles. I am the course coordinator of this course and would like to welcome you to join this exciting course in the field of extracellular vesicles or EVs. This is the second series. in this series, the course is focused on the role of extracellular vesicles in health and disease. The course is organized in collaboration between the International Society for Extracellular Vesicles and University of California Irvine, USA. In this second course on the role of EV in health and disease is made possible through collaborative work in many aspects. The lectures were created by the team of scientists and went through two steps of reviewing processes. The first one on the content of each lecture and the second one on the final presentations. The educational team of ISEV headed by professor Edit Buzas had been working together to review this lectures. I'd like to say thank you to the team of reviewers who have always been ready to jump in with the request to review these lectures. So let's talk about the course. Firstly, why are we excited about this course and the field of extracellular vesicles or EVs. EVs are known to be involved in cell to cell communication. There are known to deliver targeting and signaling molecules such as the proteins, nucleotides, lipids, and metabolites. Also, EV have been shown to mediate communication with distant organs. This course discuss recent advances made in the field to give you an introduction to their biological functions in human. It is designed for intermediate learners and also others who seek to understand more on the role of EVs. For a beginner in the field of extracellular vesicles and others who would like to learn on techniques available to study EVs, I'd like to refer to the first course led by Cecillia Lasser and can be found in Coursera with title Basics of Extracellular Vesicles. Please have a look into the overview in the next presentation. In the second course, we will study the physiological and pathophysiological role of EVs. How EVs can be involved in conveying messages to maintain healthy cells and also to mediate disease progression. Case studies and examples that were publish will be highlighted to help understand the multifunction of EV capabilities in human. This course will also discuss the role of EVs from various organisms in the context of how EVs can deliver messages from other organism and affect human health. So your grade for this course will be based on the quizzes at the end of each module. This introduction and overview of the basic extracellular vesicles are in the first module with no quizzes. The quizzes in Module 2 and 3 are worth 30 percent of your grade, while Module 4 is worth 40 percent of your grade. The passing threshold is 70 percent. Let's start with the physiological function of EVs. In this second module, we will discuss the role of extracellular vesicles in maintaining cellular homeostasis. Why they are essential for this process. We will start with how microorganisms such as bacteria can secrete EVs, the altered EV secretion as response to inflammation, stress, apoptosis and senescence will be discussed as well as examples will be provided on how EV cargo can influence cellular metabolism, and the function of EVs in maintaining physiological stage of the cells such as reported in pregnancy and in coagulation. The first lecture is prepared by Yong Song Gho and his team. This lecture covered the biogenesis of EVs by bacteria, that both gram-negative and surprisingly also gram-positive bacteria can secrete vesicles. This lecture also presents some in vivo studies on the effect of exposure of bacterial derived vesicles. Some examples of the therapeutic application of bacterial derived EVs was also presented. The second lecture covers coagulation prepared by Rienk Niewland and his team. This lecture starts with the historical evidence of how platelet derived EVs are involved in coagulation in wound healing process. EVs can also deliver tissue factor therefore increasing the risk of developing venous thromboembolism in cancer patients. Different ways to analyze EV in the context of coagulation were also discuss. The third lecture by Edit Buzas and Marca Wauben covers the role of EV in adaptive and innate immune response, where EV can affect immune cells and in response, the immune cells secrete EVs that are involved in physiological function of other cell types and also in diseases such as in cancer. EV can also transfer danger signals and cytokines, important molecules for maintaining the immune systems. In the fourth lecture, we will discuss the role of EVs in metabolism. How EVs can carry enzymes that influence the metabolic processes and also that EVs can carry the metabolites. Several conditions that were reported to influence the development of metabolic syndrome were discussed. Examples on microorganism derived EVs that carry metabolites were also presented. Juan Falcon Perez and his team prepared this lecture. The next lecture, discusses the role of EVs in pregnancy prepared by Monica Kazmarek and Chris Gardner. This lecture covers the role of EVs in the male and female reproductive tracks, the role of EVs during fertilization and pregnancy. Lecture also covers the role of EVs in pregnancy disorders such as preeclampsia, gestational diabetes, and recurrent miscarriage. The sixth lecture covered the biological significance of the EV release by stress cells by Bas van Balkom and team. This lecture shows some examples of how stress induced cells can precondition the other cells preparing those cells for a potential threat. Further, EV secreted by stress-induced cells can reflect the condition of the cells, allowing EVs to be utilized as a biomarker in many diseases. The last lecture in this module covered the topic of EV biogenesis in apoptotic and senescence cells. The definition of apoptosis and senescence were discussed, as well as the regulators and factors that are involved in this process. This structure was prepared by Ivan Poon and Hidetoshi Tahara. The third module in this course discuss the role of EVs in cancer. The module will highlight the role of EV in the progression of cancer and how the cargo delivered via EVs can directly influence cancer cell proliferation and drive metastasis. The strategies employed to utilize EV bio-marker in cancer are also covered in this module. To open this topic, a lecture presented by Dave Carter and Janus Rak, will discuss the known shared function of EVs in cancer, how they can play a role to drive cancer progression and metastasis. Various examples of cargo delivered by EVs to and from cancer cells that are involved in the development of cancer to advanced diseases were also presented. The second lecture in this module discussed the interaction between tumor and its micro-environment via EVs. How EVs can affect the surrounding endothelial cells and examples on cargo delivered by EVs to other organs. This lecture was presented by Jason Webber and Dan Lambert. In the third lecture, the complexity of how cancer cells can influence the immune system and how in reverse immune cells can transform cancer cells by delivering signaling molecules via EVs was also discussed. This comprehensive lecture also covers the bio-genesis and detailed examples on the effect of EVs on different types of immune cells. The lecture is prepared by Clotilde Thery, Mercedes Tkach and Suzanne Gabrielsson. The fourth lecture will focus on the role of EVs in maintaining a sustainable signaling for proliferation, one of the cancer hallmarks. Examples on molecules that are associated with EVs that can drive cancer proliferation and survival, as well as EV mediated drug resistance will be discussed. This lecture is prepared by myself, David Greening and Mary Bebawi. In the fifth lecture and the last lecture in this module, we will cover some of the consideration and guidelines that are important in utilising EVs as cancer biomarker. This lecture is prepared by Lorraine Driscoll and the team. This lecture also covers techniques that are commonly used to detect EVs, selection of bio-fluid for tumor EV biomarker, models that are used in studying EVs, and techniques that are used to study EV as cancer biomarker They all will be discussed in this lecture. In this fourth module, we will discuss the reported role of EVs in mediating the development of various diseases such as cardiovascular diseases, haematological disorders, disease of the nervous system, infectious diseases, neurological diseases and respiratory diseases. This module also highlight some of the proposed EV associated biomarker and some strategies in utilizing EVs for therapy of these particular diseases. The first lecture in this module covers the role of EVs in cardiovascular diseases prepared by Chantal Boulanger. The biological function of EVs in the disease of the vascular wall, development of human atherosclerotic plaques and in calcified lesions, as well as the potential role of cardiac EVs following myocardial infarction are discussed. The second and third lectures are twin lectures that will cover the role of EVs in haematology diseases. The first one is presented by Paul Harrison that includes a brief introduction of EVs and the development on the isolation procedures and analysis of EVs for hematological diseases. This lecture also cover some examples on the biological processes that are driven by platelet EVs. The second lecture is prepared by Theresa Whiteside that covers the role of EVs in haematological malignancies. Several clinical and in vitro studies and the relevance of EVs as biomarker in this disease such as in acute myeloid leukemia or AML was discussed. The fourth lecture in this module covers the role of EVs in the development of diseases of the nervous system. The lecture covers the role of EVs in the brain, their characteristic and what is known on EV secreted by neurons and glial cells. Evidence on the part of EVs in the development of neurodegenerative diseases and potential therapeutic strategies were discussed. This lecture was prepared by Andy Hill and team. The fifth lecture covers role of EVs in infectious diseases. This lecture discusses the role of EV in mediating pathogen- pathogen communication and between pathogens and hosts. Various examples are discussed on the role of EVs in malaria, chagas disease and disease caused by fungi, viral, and bacterial infections. This lecture was prepared by Neta Regev-Rudzki and the team. The sixth lecture prepared by Alicia Lorrente and her team about the role of EVs in urological diseases. This lecture covers the conditions on organs that are part of the urinary system in mammals such as kidneys, ureters, bladder, and urethra. The source of biomarkers that is relevant in urology, the urine, and bio-markers in the context of urological diseases were also discussed. The final presentation, the seventh lecture in this module covers a relatively new topic on the role of EVs in respiratory related diseases such as in chronic obstructive lung diseases or COPD and IPF idiopathic pulmonary fibrosis. This lecture also covers the reported studies on the altered EV cargos secreted by lung that was exposed to stress and injury, such as the one caused by smoking. This lecture was prepared by Takahiro Ochiya and team. So I hope that you're excited and ready to start the course. Lastly, I would like to thank the team of narrators. Excellent lectures are not possible without their enthusiasms. Special thanks also to Ken Witwer and Pia Siljander who are involved in improving the clarity of narration for some of the lectures. On behalf of ISEV and UCI, welcome to the course!
