Role of Exosomes in Biological Communication Systems

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This book reviews the role of exosomes and extracellular vesicles in both normal and pathological conditions. It first explains isolation methods for exosomes, and analyzes their fine structure and biological functions. Further, it highlights exosomes’ role as the key regulator in embryonic-maternal communication, and in the pathogenesis of various diseases, including cancer and urogenital, infectious, and neurodegenerative diseases. Moreover, it reviews the latest advances in using stem-cell-derived exosomes as a cell-free strategy in regenerative medicine, as well as the potential of exosomal microRNA as a promising non-invasive biomarker and targetable factor in cancer diagnosis and treatment. Lastly, it explores the use of natural and synthetic exosomes as nano-vehicles for efficient drug delivery.

Author(s): Faisal A. Alzahrani, Islam M. Saadeldin
Publisher: Springer Singapore
Year: 2020

Language: English
Pages: 373
City: Singapore

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