Table of contents : Preface Contents Editors and Contributors Contributors 1: Isolation and Characterization of Extracellular Vesicles: Classical and Modern Approaches 1.1 Introduction 1.2 Isolation Techniques 1.2.1 Ultracentrifugation-Based Techniques 1.2.2 Size-Based Techniques 1.2.3 Immunoaffinity Capture-Based Techniques 1.2.4 Polymer-Based Precipitation 1.2.5 Microfluidic Techniques 1.3 Characterization of Extracellular Vesicles 1.3.1 Electron Microscopy 1.3.2 Atomic Force Microscopy 1.3.3 Dynamic Light Scattering 1.3.4 Nanoparticle Tracking Analysis 1.3.5 Tunable Resistive Pulse Sensing 1.3.6 Flow Cytometry 1.3.7 Laser Tweezers Raman Spectroscopy 1.3.8 Dark-Field Microscopy 1.3.9 Fluorescence-Based Techniques 1.3.10 Surface Plasmon Resonance 1.3.11 Interferometric Imaging 1.3.12 Detection of Exosomes by Western Blot 1.4 Conclusion and Future Perspective References 2: Characterization and Fine Structure of Exosomes 2.1 Introduction 2.2 Discovery of Exosomes 2.3 What Are Exosomes? 2.4 Exosome Characterization 2.5 Exosome Characterization Methods 2.6 Nanoparticle Tracking Analysis 2.7 Dynamic Light Scattering 2.8 Tunable Resistive Pulse Sensing 2.9 Atomic Force Microscopy 2.10 Transmission Electron Microscopy 2.11 Flow Cytometry 2.12 Raman Spectroscopy 2.13 Surface Plasmon Resonance-Based Nanosensors 2.14 Nano-Deterministic Lateral Displacement 2.15 Exosome Basic Mechanisms 2.15.1 Exosome Biogenesis 2.15.2 Sorting of Cargo into Exosomes 2.15.3 Exosome Secretion 2.15.4 Cellular Homeostasis Affects Exosome Release 2.15.5 Exosome Trafficking 2.15.6 Exosome Uptake 2.15.7 Fine Structure of Exosomes Exosomal Structure and Integral Constituents 2.15.8 Exosomal Proteomics 2.15.9 Exosomal Membrane Proteins 2.16 Outer Membrane Lipid-Anchored Proteins 2.16.1 Peripheral Surface Proteins 2.16.2 Inner Membrane Lipid-Anchored Proteins 2.16.3 Inner Membrane Peripheral Proteins 2.17 Exosomal Enzymes 2.18 Bulk Inclusion and Soluble Proteins 2.19 Exosomal Glycoconjugates 2.20 Exosomal Lipids 2.21 Exosomal Nucleic Acids 2.21.1 Exosomal RNAs 2.21.2 Exosomal DNA 2.21.3 Exosome Functions 2.21.4 Exosomes in Angiogenesis 2.21.5 Exosomes in Apoptosis 2.21.6 Exosomes in Inflammation 2.21.7 Exosomes as Biomarkers 2.21.8 Receptor-Mediated Endocytosis and Exosomes 2.21.9 Cell Proliferation and Exosomes 2.22 Future Directions References 3: Extracellular Vesicles Mediate the Embryonic-Maternal Paracrine Communication 3.1 Introduction 3.2 Embryo-Derived Extracellular Vesicles 3.2.1 The Proof of Release of Extracellular Vesicles from Embryos 3.2.2 Proof of Transfer of Extracellular Vesicles to the Embryos 3.2.3 Embryo-Derived Extracellular Vesicles Indicate the Embryo Quality and Sexual Dimorphism 3.2.4 Embryo-Derived Extracellular Vesicles Modulate Endometrium Functions 3.2.5 Challenges with Embryo-Derived Extracellular Vesicles 3.3 Oviduct-Derived Extracellular Vesicles 3.3.1 Oviduct Extracellular Vesicles Modulate Cumulus-Oocyte Complex 3.3.2 Oviduct Extracellular Vesicles Modulate Spermatozoa Functions 3.3.3 Oviduct Extracellular Vesicles Modulate Embryo Development 3.3.4 Juxtacrine/Paracrine Actions of Oviduct Extracellular Vesicles 3.3.5 Oviduct Extracellular Vesicle Profile in Estrous Cycle Phases 3.4 Endometrium-Derived Extracellular Vesicles 3.4.1 Endometrium-Derived Extracellular Vesicle Screening and Profiling 3.4.2 Endometrium-Derived Extracellular Vesicles Modulate Embryo Development 3.4.3 Endometrium-Derived Extracellular Vesicles Modulate Embryo Adhesion and Implantation 3.4.4 Pathogenesis of Early Embryonic Loss Through Extracellular Vesicles 3.5 Concluding Remarks References 4: The Interplay Between Oviduct-Derived Exosomes and Cumulus-Oocyte Complexes 4.1 Physiological Characteristics of Exosomes 4.2 The Application of Exosomes on the Field of Reproduction 4.3 Overview of Oviduct-Derived Extracellular Vesicles/Exosomes in the Field of Reproduction 4.4 The Interaction Between Oviduct-Derived Exosomes and Cumulus-Oocyte Complexes 4.4.1 Isolation of Oviduct-Derived Exosomes from Oviduct Cells 4.4.2 Characterization and Identification of Oviduct-Derived Exosomes 4.4.3 The Interplay Between Oviduct-Derived Exosomes and Cumulus Cells 4.4.4 The Interplay Between Oviduct-Derived Exosomes and Cumulus-Oocyte Complexes 4.5 Concluding Remarks References 5: The Interplay Between Exosomes and Spermatozoa 5.1 Introduction 5.2 Mechanisms of Cellular Protein Release 5.3 Maturation of Spermatozoa 5.4 Male Reproductive Tract-Derived Exosomes 5.4.1 Epididymis-Derived Exosomes Discovery of Epididymosomes Composition of Epididymosomes Spermatozoa-Epididymosome Interaction 5.4.2 Vas Deferens-Derived Exosomes 5.4.3 Accessory Sex Gland-Derived Exosomes Mechanism of Prostasome Release Composition of Prostasomes Spermatozoa-Prostasome Interaction 5.5 Female Reproductive Tract-Derived Exosomes 5.5.1 Uterosomes and Spermatozoa 5.5.2 Oviductosomes and Spermatozoa 5.6 Semen Freezing and Exosomes 5.6.1 Effect of Exosomes on Motility and Viability 5.6.2 Effect of Exosomes on Structural Integrity 5.6.3 Effect of Exosomes on Capacitation of Spermatozoa 5.6.4 Effect of Exosomes on Antioxidant Capacity 5.7 Conclusion References 6: Mesenchymal Stem Cell-Derived Exosomes and Regenerative Medicine 6.1 Introduction 6.2 Exosome Biogenesis 6.3 Exosome Content 6.3.1 Proteins Membranous Protein Cytosolic Proteins Mitochondrial Proteins 6.3.2 Lipids 6.3.3 Nucleic Acids 6.4 Methods of Exosome Isolation and Characterization 6.5 Factors Influencing the Quality of Stem Cell Exosomes 6.5.1 Cell Source and Manipulation Donor Age Gender Fasting Cell Tissue Sources Disease 6.5.2 Cell Culture Type 6.5.3 Cell Culture Condition 6.5.4 Isolation Methods 6.6 Biological Function 6.6.1 Homing Capacity 6.6.2 Enhance Cell Viability Proliferation and Inhibit Apoptosis 6.6.3 Promote Cell Differentiation Osteogenic Differentiation Chondrogenic Differentiation Cardiomyogenic Differentiation Neural Differentiation 6.6.4 Enhance Cell Migration 6.6.5 Anti-inflammatory 6.6.6 Antifibrotic Effect 6.6.7 Antioxidant Effect (Reduction of Oxygen-Free Radicals) 6.6.8 Promote Blood Vessel Formation and Fibroblast Function 6.6.9 Matrix Integrity 6.7 Conclusion and Future Perspectives References 7: Therapeutic Potential of Mesenchymal Stem/Stromal Cell-Derived Exosomes 7.1 Mesenchymal Stem/Stromal Cells 7.2 Exosomes 7.3 Therapeutic Applications of Mesenchymal Stem/Stromal Cell-Derived Exosomes 7.4 Pre-conditioning of Mesenchymal Stem/Stromal Cell-Derived Exosomes to Enhance Therapeutic Efficacy 7.5 Concluding Remarks References 8: Exosomes in Neurodegenerative Disorders 8.1 Exosomes and the Nervous System 8.1.1 Presynaptic Vesicles Versus Exosomes 8.1.2 Exosomal Release and Regulation 8.1.3 Physiological Functions of Exosomes in the Nervous System 8.2 Exosomes and Neurodegeneration 8.2.1 Role of Exosomes in the Pathology of Alzheimer´s Disease 8.2.2 Role of Exosomes in the Pathology of Parkinson´s Disease 8.2.3 Role of Exosomes in the Pathology of Multiple Sclerosis 8.2.4 Role of Exosomes in the Pathology of Amyotrophic Lateral Sclerosis 8.2.5 Role of Exosomes in the Pathology of Prion Diseases 8.3 Exosomes for the Diagnosis of Neurodegenerative Diseases 8.3.1 Role of Exosomes in the Diagnosis of Alzheimer´s Disease 8.3.2 Role of Exosomes in the Diagnosis of Parkinson´s Disease 8.3.3 Role of Exosomes in the Diagnosis of Multiple Sclerosis 8.3.4 Role of Exosomes in the Diagnosis of Amyotrophic Lateral Sclerosis (ALS) 8.3.5 Role of Exosomes in the Diagnosis of Prion Diseases 8.4 Exosomes for the Therapy of Neurodegenerative Diseases References 9: Differential Expression of Exosomal MicroRNAs in Neurodegenerative Diseases 9.1 Exosomal miRNAs 9.2 Parkinson´s Disease 9.2.1 Prevalence and Symptoms of PD 9.2.2 The Molecular Change in the Cerebrospinal Fluid of PD Patients 9.3 Alzheimer´s Disease 9.3.1 The Pathophysiology of Alzheimer´s Disease and Challenges of Diagnosis 9.3.2 The Role of miRNAs in Alzheimer´s Disease Progression 9.4 Schizophrenia 9.4.1 The Molecular Changes Associated with Schizophrenia 9.5 Bipolar Disorder 9.6 Conclusion References 10: Urinary Exosomes as a Possible Source of Kidney Disease Biomarkers 10.1 Introduction 10.2 Biogenesis and Structural Composition of Urinary Exosomes 10.2.1 Biogenesis of Urinary Exosomes 10.2.2 Structural Composition of Urinary Exosomes 10.3 Isolation of Urinary Exosomes 10.3.1 Isolation of Protein from Exosomes 10.3.2 Isolation of RNA from Exosomes 10.4 Urinary Exosome Protein Markers 10.5 Urinary Exosome-Derived Biomarkers 10.6 Challenges 10.7 Conclusion References 11: Extracellular Vesicles as Potential Therapeutic Targets and Biomarkers for Liver Disease 11.1 Introduction 11.2 EVs as Promising Biomarkers for Drug-Induced Liver Injury 11.3 The Potential Diagnostic Role of EVs in Alcohol-Related Liver Disease 11.4 The Potential Functions of EVs in Viral Hepatitis 11.5 The Immunological Role of EVs in Hepatitis B 11.6 The Importance of EVs in Hepatitis C and A 11.7 The Potential Role of EVs in Oxidative Stress and Inflammation in Hepatic Diseases 11.8 Carcinogenesis, Diagnosis, and the Therapeutic Potential of EVs in Hepatocellular Carcinoma 11.9 Conclusions References 12: Implications of Extracellular Vesicles in Blood Protozoan Parasitic Diseases 12.1 Introduction 12.2 Implications of Extracellular Vesicles in Trypanosomiasis 12.3 Implications of Extracellular Vesicles in Leishmaniasis 12.4 Implications of Extracellular Vesicles in Malaria 12.5 Potential Uses of Extracellular Vesicles in Blood-Borne Parasitic Diseases 12.6 Conclusion References 13: Cancer Cells-Derived Exosomes and Metastasis 13.1 Introduction 13.2 The Role of Exosomes in Modulating Tumour Microenvironment 13.3 The Role of Cancer Cells-Derived Exosomes in Angiogenesis Establishment 13.4 The Role of Exosomes in the Formation of Premetastatic Niche 13.5 The Role of Exosomes in Inducing Cell Motility and Invasion 13.6 The Role of Exosomes in Modulating the Immune System 13.7 Conclusion References 14: Extracellular Vesicles and Integrins: Partners in Cancer Progression 14.1 Introduction 14.2 Integrins and Extracellular Vesicle-Integrins in Tumor Development 14.3 Extracellular Vesicles and Integrins in Epithelial-Mesenchymal Transition 14.4 Extracellular Vesicles and Integrins in Angiogenesis 14.5 Extracellular Vesicles and Integrins in Cell Invasion and Migration 14.6 Extracellular Vesicle-Derived Integrins and Metastatic Colonization 14.7 Conclusions and Perspectives References 15: Exosomes: The Crucial Element in Prostate Cancer 15.1 Introduction 15.2 The Origin of Prostate Cancer Stem Cells 15.3 Prostate Cancer Stem Cells Express the Exosomes 15.4 The Utility of Exosomes in Diagnosis and Treatment of Prostate Cancer 15.5 Conclusion References 16: Exosomal microRNAs: Potential Biomarkers for Cancer Diagnosis, Treatment Response and Prognosis 16.1 Introduction 16.2 Exosomal microRNAs: Definition, Origin and Function 16.3 Exosomal microRNA as a Liquid Biopsy for Cancer 16.4 Exosomal microRNAs as Novel Biomarkers for Clinical Diagnosis 16.5 Exosomal microRNAs as Predictors and/or Indicators of Treatment Response 16.6 Exosomal microRNAs to Distinguish Cancer Subtypes 16.7 Exosomal microRNA as Predictor of Cancer Recurrence and Metastasis 16.8 Concluding Remarks References 17: Exosomes in Drug Delivery 17.1 Introduction 17.2 Composition and Characterization of Exosomes 17.3 Function of Exosomes 17.3.1 Roles of Exosomes in Immunity and Their Protective and Regenerative Effects 17.3.2 Roles of Natural Cargoes Loaded in Exosomes 17.4 Therapeutic Cargoes in Exosomes 17.4.1 Passive Encapsulation 17.4.2 Active Encapsulation 17.5 Exosomes and Nanocarriers: Similarities and Differences 17.6 Exosome-Based Drug Delivery Strategies 17.6.1 Delivery of Therapeutic Small Molecules 17.6.2 Delivery of Therapeutic Proteins 17.6.3 Delivery of Therapeutic Nucleic Acids 17.7 Major Advantages and Disadvantages of Using Exosomes as Carriers 17.8 Conclusion and Future Perspectives References 18: Exosomes and Supported Lipid Layers as Advanced Naturally Derived Drug Delivery Systems 18.1 Lipid-Based Carriers 18.2 Naturally Derived Lipid-Based Carriers 18.2.1 Exosomes Innate Functions of Exosomes Drug Delivery Applications of Exosomes Loading Techniques of Exosomes with Therapeutic Agents 18.2.2 Cell Membrane-Based Supported Lipid Bilayer Journey from Synthetic to Natural Cell Membrane Extraction Methods Delivery Applications of Naturally Derived Supported Lipid Bilayer Nanoparticles 18.3 Conclusion References