New Frontiers: Extracellular Vesicles

Description

The field of extracellular vesicles (EVs) has progressed immensely in recent times with evidences highlighting their importance in physiology and pathology. This book entails extensive reflective literature on many subtypes of EVs including exosomes, exomeres, ectosomes, apoptotic vesicles, bacterial EVs and fungal EVs. The book further discusses the biogenesis and secretion of these EVs, detailing the biological pathways and proteins involved. Research investigating the biological functions of EVs is rapidly increasing and the current knowledge around their role in progression of diseases such as cancer, neurodegeneration and metabolic disorders is discussed in multiple chapters. The implications of EVs in intercellular communication and the significance of biologically active cargo carried within these EVs are further examined. Moreover, the numerous applications of EVs in diagnostics and treatment of diseases are reviewed in detail, particularly their potential as biomarkers and drug delivery vehicles. Taken together, this book is a compilation of the key implications of EVs that are secreted by virtually all cell types. Readers will gain a perspective into the biology, functions and applications of EVs and their constantly evolving knowledge base. Preface EVs: A Diverse Community Functional Role and Clinical Implications of EVs Contents About the Editors Part I: Subtypes, Biogenesis, and Secretion of Extracellular Vesicles Chapter 1: Introduction to the Community of Extracellular Vesicles Introduction Subtypes of EVs Molecular Composition of EVs Isolation and Characterisation of EVs Concluding Remarks References Chapter 2: Biogenesis of Extracellular Vesicles Introduction: Extracellular Vesicles Large Oncosomes Apoptotic Bodies Migrasomes Ectosomes/Shedding Microvesicles Exosomes ESCRT-Dependent Pathway of ILV Biogenesis ESCRT-Independent Pathway of ILV Biogenesis Role of Tetraspanins in Biogenesis of Exosomes Secretion of Exosomes Exomeres Concluding Remarks References Chapter 3: The Role of Post-Translational Modifications in Targeting Protein Cargo to Extracellular Vesicles Introduction Phosphorylation Glycosylation Ubiquitination SUMOylation Oxidation Citrullination ISGylation Myristoylation Palmitoylation Concluding Remarks References Chapter 4: Apoptotic Bodies: Mechanism of Formation, Isolation and Functional Relevance Introduction Mechanisms of Apoptotic Cell Disassembly Step 1: Plasma Membrane Blebbing Step 2: Apoptotic Membrane Protrusion Formation Pannexin 1 Plexin B2 Cytoskeleton Vesicle Trafficking Step 3: ApoBD Fragmentation Maintenance of Plasma Membrane Integrity to Prevent Premature Lysis Methods of ApoBD Isolation Differential Centrifugation Filtration Fluorescence-Activated Cell Sorting (FACS) Validation of ApoBDs Functional Significance of ApoBD Formation ApoBDs in Cell Clearance ApoBDs in Intercellular Communication Intercellular Communication Through DNA as Cargos Intercellular Communication Through RNA as Cargos Intercellular Communication Through Proteins as Cargos Intercellular Communication Through Pathogen-Derived Material Concluding Remarks References Chapter 5: Exomeres: A New Member of Extracellular Vesicles Family Introduction Exomeres Proteomic Cargo of Exomeres Isolation of Exomeres Concluding Remarks References Part II: Functional Role and Clinical Implications of Extracellular Vesicles Chapter 6: Pathogenesis Mediated by Bacterial Membrane Vesicles Introduction What are Bacterial Membrane Vesicles? The Study of BMVs Isolation and Purification Characterisation & Analysis BMV Biogenesis Mechanisms of OMV Biogenesis Mechanisms of MV Biogenesis Cargo Packaging into BMVs Physiological Roles of BMVs Physiological Roles of OMVs Produced by Gram-Negative Bacteria Biofilm Formation Nutrient Acquisition Competition and Predation Bacterial Defence Horizontal Gene Transfer Physiological Roles of MVs Produced by Gram-Positive Bacteria Pathogen-Derived BMVs Can Modulate the Host Immune Response Pathogenic Functions of BMVs at the Mucosal Surface Pathogenic BMVs Can Disrupt the Epithelial Barrier BMVs Can Enter Host Epithelial Cells BMVs Mediate Innate Immune Signalling in Epithelial Cells TLRs at the Apical and Endosomal Membranes Detect BMVs Bacterial sRNA Delivery by OMVs and MVs Intracellular Activation of NLRs BMVs can cross the epithelial cell barrier BMVs and Macrophages BMVs and Neutrophils BMVs and DCs BMVs and Adaptive Immune Cells Microbiota-Derived BMVs Modulate Immune Responses BMVs in Host-Microbiota Interactions at Mucosal Surfaces Commensal BMVs Mediate Long-Distance Anti-Inflammatory Effects Applications of BMVs BMVs as Vaccine Candidates BMVs as Novel Therapeutics Drug Delivery Novel Technologies Utilising BMVs Conclusions and Perspectives References Chapter 7: Fungal Extracellular Vesicles in Pathophysiology The Impact of Fungi on Human Health The Impact of Fungi on Agriculture Characteristics Unique to Fungal EVs The Fungal Cell Wall Impacts EV Content Fungal EVs Must Traverse the Cell Wall to Reach the Host Emergence of Protein Markers for Fungal EVs Role of Fungal EVs in Pathophysiology Interactions of Yeast EVs with the Host Immune System Interactions of Mycelial EVs with the Host Immune System EV Content from Human Fungal Pathogens Suggests a Role in Virulence Protein RNA Carbohydrates Lipids Prions Fungal EVs in Drug Resistance EVs from Fungal Plant Pathogens Contain Molecules Related to Virulence Conclusion References Chapter 8: Socially Distanced Intercellular Communication: Mechanisms for Extracellular Vesicle Cargo Delivery Intercellular Communication Extracellular Vesicles EV Biogenesis and Cargo Packaging Microvesicles Exosomes Exosome Biogenesis Exosome Secretion Cargo Loading Apoptotic Bodies EV Isolation and Origins Evidence for Cargo Delivery by EVs Evidence for Cargo Transfer by EVs Evidence for Functional Cargo Delivery Questions Regarding Biological Relevance Underlying Cellular Mechanisms Proposed for EV Communication and Cargo Delivery Binding to Cell Surface Receptors Cargo Delivery within the Recipient Cell Plasma Membrane Fusion Supporting Evidence for Plasma Membrane Fusion Fusion within the Endo-Lysosomal System Endocytosis Early/Sorting Endosome Late Endosome and MVB Lysosome Supporting Evidence for Fusion within the Endo-Lysosomal System Other Delivery Sites Summary, Open Questions and Challenges References Chapter 9: Extracellular Vesicles in Chemoresistance Introduction Multidrug Resistance ABC Transporters P-Glycoprotein Multidrug Resistance Associated-Protein 1 Breast Cancer Resistance Protein Pharmacological Inhibition of ABC Transporters as a Strategy to Overcome MDR Extracellular Vesicles in the Dissemination of Cancer Drug Resistance Transfer of Functional ABC Transporter Proteins Transfer of Other Proteins Transfer of RNA mRNA miRNA lncRNA Transfer of Lipids Beyond the Transfer of Drug Resistance: EVs Mediate a Complex Survival Phenotype Sequestration of Cytotoxic Drugs and EV-Mediated Drug Efflux EV-Mediated Stimulation of Cancer Cell Invasion and Metastatic Capacity EV-Induced Evasion from the Immune System EVs as a Therapeutic Target in the Treatment of Multidrug Resistance EVs as Biomarkers of Multidrug Resistance Summary References Chapter 10: Extracellular Vesicle Mediated Vascular Pathology in Glioblastoma Introduction: Vascular Consequences of Malignant Transformation Brain Tumour Vasculature Glioblastoma Brain Tumour EVs: Heterogeneity and Function Evidence for the Role of EVs in Tumour Angiogenesis EV-Related Processes of Blood Vessel Formation in Glioblastoma Brain Tumour Associated Coagulome and Coagulopathy Procoagulant EVs in Brain Tumours Conclusions References Chapter 11: Extracellular Vesicles Regulate Cancer Metastasis Introduction What Are Extracellular Vesicles? Metastatic Cancer EVs as Communicative Vessels of Cancer Progression Cellular Communication Influencing Recipient Cell Phenotype Angiogenesis and Vascular Leakiness Extracellular Matrix Remodeling Immune Modulation and Evasion Role of Extracellular Vesicles in Axonogenesis Recruitment and Education of Stem/Progenitor Cells Organ Specificity in Cancer Metastasis, `Seed, Soil and Fertilizer Concept´ Mechanisms of Metastasis Via EV Mediated Pre-Metastatic Niche Formation Targeting EVs for the Inhibition of Cancer Metastasis Conclusion References Chapter 12: Extracellular Vesicle-Mediated Bone Remodeling and Bone Metastasis: Implications in Prostate Cancer Introduction The Bone Remodeling Cycle: Cellular and Molecular Mechanisms Regulation of Bone Remodeling Via CrossTalk Amongst Bone Cells Osteoclast-Osteoblast Communication Osteocyte-Osteoblast Communication Osteocyte-Osteoclast Communication Extracellular Vesicles: Novel Regulators of Bone Remodeling and Skeletal Metabolism The Characteristics and Contents of Bone-Derived Extracellular Vesicles Role of Bone-Derived Extracellular Vesicles in Bone Homeostasis Role of Osteoclast-Derived Extracellular Vesicles Role of Osteoblast-Derived Extracellular Vesicles Role of Osteocyte-Derived Extracellular Vesicles Prostate Cancer Bone Metastasis Altered Bone Remodeling and the Underlying Bone-Tumor Cell Crosstalk in Bone Metastasis Osteolytic Metastasis Osteoblastic Metastasis Role of Extracellular Vesicles in Prostate Cancer Bone Metastasis The Involvement of Extracellular Vesicle RNA Cargo in Prostate Cancer Bone Metastasis Understanding Vesicle Cargo Sorting and Selection of Metastasis-Inducing Molecules Conclusions References Chapter 13: Extracellular Vesicles Contain Putative Cancer Biomarkers Introduction EVs Are Reservoirs of Cancer Biomarker Candidates Tumor-Derived EVs as Source of Cancer Biomarkers Conclusion References Chapter 14: Engineering Extracellular Vesicles for Cancer Therapy Introduction Functions and Sources of EVs for Therapeutic Applications Specific Targeting and Modification of EVs for Cancer Therapy Methods for Loading Therapeutic Agents and Molecules into EVs Clinical Applications of EVs for the Treatment of Cancer: Advancements and Limitations Prospects and Concluding Remarks References Chapter 15: Extracellular Vesicles in Metabolism and Metabolic Diseases Introduction Overview of Metabolism and Metabolic Pathways Extracellular Vesicles: Composition and Functions EVs as Metabolic Messengers EVs in Metabolic Diseases EVs in Cancer Metabolism and Progression Concluding Remarks References Chapter 16: Extracellular Vesicles in Neurological Disorders Introduction Extracellular Vesicles in Brain Development and Developmental Disorders Autism Spectrum Disorder Epilepsy Schizophrenia Cancers Prion Diseases Parkinson´s Disease Alzheimer´s Disease Amyotrophic Lateral Sclerosis Concluding Remarks References Chapter 17: Emerging Roles of Extracellular Vesicles Derived Non-Coding RNAs in the Cardiovascular System Introduction Role of EV Derived Small RNAs in the Cardiovascular System Role of EV Derived miRNAs in Cardiovascular Cells Stem Cell-Derived EV-miRs Endothelial Progenitor Cell-Derived EV-miRs in Cardiac Repair Mesenchymal Stem/Stromal Cell-Derived EV-miR in Cardiac Repair Role of Cardiac Stem/Progenitor Cells Derived EV-miR in Cardiac Repair Role of Pluripotent Stem Cells Derived EV-miRs in Cardiac Repair Role of EV-Derived Y-RNA in the Cardiovascular System Role of EV-Derived lncRNA in the Cardiovascular System Role of EV-Derived circRNA in the Cardiovascular System Conclusions References Chapter 18: Extracellular Vesicles and Preeclampsia: Current Knowledge and Future Research Directions Introduction Pathophysiology of PE EVs Heterogeneity and Biogenesis Profiling EVs in Biological Fluids Content of EVs from PE Compared to Normal Bioactivity of EVs Compared to Normal Placental Alkaline Phosphatase (PLAP) Profiling EVs Using In Vitro and Ex Vivo Systems Summary and Future Directions References Chapter 19: The Role of Extracellular Vesicles in Sperm Function and Male Fertility Introduction Role of EVs in the Male Reproductive Tract on Sperm Function Epididymis Prostate Role of EVs in the Female Reproductive Tract on Sperm Function Uterus and Vagina Oviduct EVs in Male Infertility Concluding Remarks References Chapter 20: Extracellular Vesicles and Cerebral Malaria Identification of MV as Important Players in CM Immune-Related Properties of MV Therapeutic Efficacy of MV Inhibition in CM Exosomes in Malaria Parasite Biology Conclusions References Chapter 21: Are Dietary Extracellular Vesicles Bioavailable and Functional in Consuming Organisms? Extracellular Vesicles Dietary EVs in Cross-Species and Kingdom Communication Pitfalls and Limitations of Dietary EV Studies Concluding Remarks References Index