Exosome Communication

Advances in Research and Therapeutics for Health and Disease

1st Edition - November 15, 2024
Imprint: Academic Press
Authors: Dalapathi Gugulothu, Dharmendra Kumar Khatri, Lalitkumar K. Vora, William C.S. Cho
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 3 - 2 9 0 5 2 - 7
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 2 9 0 5 3 - 4

Exosome Communication: Advances in Research and Therapeutics for Health and Disease serves as a crucial reference for pharmaceutical scientists, focusing on the key qualit… Read more

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Exosome Communication: Advances in Research and Therapeutics for Health and Disease serves as a crucial reference for pharmaceutical scientists, focusing on the key qualities of exosomes as drug delivery vehicles. Exosomes are intracellular membrane-based vesicles with diverse compositions, offering significant advantages over traditional drug delivery systems such as liposomes and polymeric nanoparticles, due to their nonimmunogenic nature. This book provides a comprehensive exploration of exosomes, starting with their history and development, understanding extracellular vesicles and biogenesis, and techniques for isolation and characterization. This book also addresses critical considerations like quality control, heterogeneity reduction, regulatory and ethical aspects, clinical trials, and scale-up manufacturing.

Title of Book
Cover image
Title page
Table of Contents
Copyright
Contributors
Chapter 1. Introduction: History and development of exosomes nanovesicles
1.1 Introduction
1.1.1 Early observation and historical context
1.1.2 Evolution of EXO terminology and nomenclature
1.1.3 Pioneering studies in EXO research
1.1.4 Milestones in EXO NV research
1.1.5 Emerging paradigms and future direction
1.2 Conclusion
Chapter 2. Exploring extracellular vesicles: Understanding exosomes and beyond
2.1 Introduction
2.2 Biogenesis and composition of exosomes
2.2.1 Cellular pathways involved in exosomes biogenesis
2.2.1.1 Endosomal sorting complex required for transport (ESCRT) pathway
2.2.1.2 ESCRT independent pathways
2.2.2 Composition of exosomes
2.2.2.1 Proteins
2.2.2.2 Nucleic acids
2.2.2.3 Lipids
2.2.2.4 Carbohydrates
2.3 Function of exosomes in cellular communication
2.3.1 Intercellular communication
2.3.2 Immune regulation
2.3.3 Waste management and cellular remodeling
2.3.4 Angiogenesis and vascular homeostasis
2.4 Beyond exosomes—Microvesicles and apoptotic bodies
2.4.1 Microvesicles
2.4.2 Apoptotic bodies
2.5 Profiling extracellular vesicles cargo: Insights into molecular signatures
2.5.1 Methodologies for cargo profiling
2.5.1.1 Proteomics
2.5.1.2 Genomics and transcriptomics
2.5.1.3 Lipidomics
2.5.2 Molecular signatures of exosomes
2.5.2.1 Surface markers
2.5.2.2 Cargoes reflecting cellular state
2.5.2.3 Functional proteins
2.6 Extracellular vesicles as diagnostic and therapeutic tools: Breakthroughs and challenges
2.6.1 Diagnostic applications
2.6.1.1 Biomarker discovery
2.6.1.2 Liquid biopsies
2.6.2 Therapeutic potentials
2.6.2.1 Drug delivery vehicles
2.6.2.2 Regenerative medicine
2.6.3 Breakthroughs
2.6.3.1 Precision medicine
2.6.4 Challenges
2.7 Future directions and conclusion
Chapter 3. Exosome isolation techniques: Methods, protocols, and best practices
3.1 Introduction to exosomes isolation
3.1.1 Discovery and definition
3.1.2 Structure and composition
3.1.3 Types of exosomes
3.1.4 Exosomes biogenesis
3.1.5 Exosome release
3.1.6 Exosome uptake
3.2 Isolation of exosomes from biological materials
3.2.1 Isolation from cell culture
3.2.2 EVS extraction from blood
3.2.3 EVS separation from tissue
3.3 Exosome extraction methodologies
3.3.1 Ultracentrifugation
3.3.1.1 Differential ultracentrifugation
3.3.1.2 Density gradient ultracentrifugation (DGUC)
3.3.2 Precipitation
3.3.3 Size based technique
3.3.3.1 Ultrafiltration
3.3.3.2 Size exclusion chromatography (SEC)
3.3.4 Affinity capture with biopolymers
3.3.5 Molecular Imprinted Polymers (MIP)
3.3.6 Microfluidic technologies for exosome isolation
3.3.6.1 Immunological separation
3.3.6.2 Trapping on porous structures
3.3.6.3 Sieving
3.4 Challenges of separation methods
3.5 Summary and conclusion
Chapter 4. Improving cargo loading and release strategies for exosomes nanovesicles
4.1 Introduction
4.2 Role of EXOs in targeted drug delivery
4.2.1 Role of EXOs in tumor development
4.2.2 Role of EXOs in disease diagnosis
4.2.3 Role of EXOs for wound healing
4.2.4 Advantages of EXOs as drug carriers
4.3 Various strategies for cargo loading into EXOs
4.3.1 Incubation
4.3.2 Cell transfection
4.3.3 Physical treatments
4.3.3.1 Electroporation
4.3.3.2 Sonication
4.3.3.3 Freeze thaw method
4.3.3.4 Extrusion
4.3.4 Surfactant treatment
4.3.5 Dialysis
4.4 In situ assembly and synthesis
4.5 Emerging paradigms in cargo loading
4.5.1 EXOs derived from tumor cells
4.5.2 Bronchial fibroblast-derived EXOs
4.5.3 Osteoclast-derived EXOs
4.5.4 Rhabdomyosarcoma (RMS) derived EXOs
4.5.5 Milk-derived EXOs
4.6 Conclusion
Chapter 5. Exosome characterization techniques, composition analysis and contents of exosomes nanovesicles: Methods and interpretation
5.1 Introduction
5.2 Morphological characterization techniques: EM and AFM
5.3 Molecular analysis of EXO composition
5.4 Advanced technologies in EXO characterization
5.5 Data interpretation and insights
5.6 Future directions and emerging techniques in EXO characterization
5.7 Conclusion
Chapter 6. Quality control, minimizing heterogeneity and enhancing yield in exosome isolation and production
6.1 Introduction
6.1.1 Quality control in exosome isolation
6.1.1.1 Quantification methods
6.1.1.2 Morphology assessment
6.1.2 Minimizing heterogeneity in exosome isolation
6.1.2.1 Biogenesis of exosome populations and subpopulations
6.1.2.2 Stochasticity
6.1.3 Enhancing yield in exosome production
6.1.3.1 Selection of stem cells
6.1.3.2 Culture methods of stem cells
6.1.3.3 Isolation of exosomes
6.1.3.4 Artificial exosomes
6.1.4 Standardized protocols for large-scale production
6.1.5 Quality control measures for exosome characterization
6.1.5.1 Importance of quality control in exosome studies
6.1.5.2 Criteria for exosome quality assessment
6.1.5.3 Quantitative, qualitative, and single vesicle characterization methods
6.1.6 Practical approaches and best practices
6.1.6.1 As delivery system for therapeutic applications
6.1.6.2 Loading approaches
6.1.6.3 Disease diagnosis
6.1.6.4 Exosome modification for targeted delivery to specific tissues or cells
6.2 Conclusion and future Directions
Chapter 7. Inhibition of cell-cell communication in exosomes
7.1 Introduction
7.2 Mechanisms of exosome-mediated communication
7.2.1 Exosome biogenesis and release
7.2.2 Cargo loading and content diversity in exosomes
7.2.3 Uptake mechanisms by recipient cells
7.3 Targeting exosome biogenesis inhibition
7.3.1 Inhibitors of exosome biogenesis pathways
7.3.1.1 Exosome release by calcium (Ca2+) regulation
7.3.1.2 Exosome release by cellular acidification
7.3.1.3 Exosome inhibitors targeting Ras-related protein (RAB27A)
7.3.1.4 Small molecules affecting lipid metabolism
7.3.1.5 Others
7.3.2 Disrupting exosome uptake
7.3.2.1 Inhibitors of receptor-mediated endocytosis
7.3.3 Therapeutic applications of exosome inhibitors
7.4 Conclusion
Chapter 8. Bioengineering and modification of exosome nanovesicles for targeted drug delivery
8.1 Introduction
8.2 Understanding and leveraging exosomes
8.2.1 Biogenesis
8.2.2 Compositions and biological functions
8.2.3 Isolation techniques
8.2.4 Loading approaches for therapeutic cargo
8.3 Need for bioengineering strategies
8.4 Bioengineering strategies for targeted delivery
8.4.1 Genetic engineering
8.4.2 Chemical modification
8.4.3 Exosome-nanoparticle hybrids
8.5 State-of-the-art examples
8.5.1 Cancer therapy
8.5.2 Inflammation and autoimmune disorders
8.5.3 Regenerative medicine
8.6 Challenges and potential solutions
8.7 Concluding remark
Chapter 9. Challenges in exosome nanovesicle-based drug delivery and diagnostics
9.1 Introduction and background
9.2 Exosomes in drug delivery
9.3 Exosomes in disease diagnosis
9.4 Challenges in clinical application
9.4.1 For drug delivery
9.4.1.1 Biological variability
9.4.1.2 Scalability and manufacturing
9.4.1.3 Storage and stability
9.4.1.4 Regulatory and safety issues
9.4.2 For disease diagnosis
9.4.2.1 Sensitivity and specificity
9.4.2.2 Standardization of the diagnostic protocol
9.4.2.3 Technological/instrumentation limitations
9.4.2.4 Economic barriers
9.5 Future prospects and concluding remarks
Chapter 10. Diagnostic potential and biomarkers potential of exosome nanovesicles
10.1 Introduction
10.2 Exosome characteristics: Favorable features as biomarkers
10.2.1 Physical and surface characteristics of exosomes
10.2.2 Biomarker potential of exosomes
10.2.3 Exosome nanovesicles as diagnostic carriers
10.2.4 Advantages of exosomes as diagnostic aids
10.3 Exosomes in disease diagnosis
10.3.1 Isolation of exosomes
10.3.2 Exosome characterization
10.3.3 Biochemical analysis of exosomal cargo
10.4 Diagnostic and biomarker potential of exosomes in cancer
10.4.1 In leukemias
10.4.2 In lung cancer
10.4.3 In breast cancer
10.4.4 In other cancers
10.5 Diagnostic and biomarker potential of exosomes in neurodegenerative disorders
10.5.1 CNS- cell specific markers
10.5.2 In Alzheimer's disease
10.5.3 In Parkinson's disease (PD)
10.5.4 Exosomes in other NDDS
10.6 Diagnostic and biomarker potential of exosomes in immune disorders
10.7 Diagnostic and biomarker potential of exosomes in other diseases
10.7.1 In cardiovascular diseases
10.7.2 In liver diseases
10.8 Challenges and way forward
Chapter 11. Immunological exosomes: An upcoming cue for disease management
11.1 Introduction
11.2 Exosome's biogenesis and distribution
11.3 Exosomes and immune system
11.3.1 Innate immune response
11.3.2 Adaptive immune response
11.4 Exosomes in pathology
11.4.1 Cancer
11.4.2 Joint and bone diseases
11.4.3 Dental diseases
11.4.4 Ophthalmic disease
11.4.5 Neurological disease
11.4.6 Cardiovascular complications
11.4.7 Reproductive diseases
11.5 Prognostic avenue of exosomes
11.6 Recent advancement and challenges of exosome-based disease management
11.7 Conclusion
Chapter 12. Exosomes for protein and peptide drug delivery
12.1 Introduction
12.1.1 Biogenesis of exosomes
12.1.2 Separation and purification of exosomes
12.1.3 Drug loading
12.1.4 Hybrid method for loading
12.2 Exosomes for peptide delivery
12.2.1 Ophthalmic delivery
12.2.2 Cardiac delivery
12.2.3 Osteoarthritis
12.2.4 Spinal cord injury
12.2.5 Hepatic delivery
12.2.6 Central nervous system
12.2.7 Immunotherapy
12.2.8 Cancer
12.3 Applications of exosomes-based protein delivery
12.3.1 Hepatic delivery
12.3.2 Lymphatic delivery
12.3.3 CNS delivery
12.3.4 Anticancer therapy
12.3.5 Muscular dystrophy
12.3.6 Biomedical application
12.3.7 Immunization
12.3.8 CNS disorders
12.3.9 Miscellaneous
12.4 Conclusion and future perspective
Chapter 13. Exosomes nanovesicles for gene delivery and vaccination
13.1 Introduction
13.2 Exosome as nanocarrier
13.2.1 Background and brief overview
13.2.2 Key characteristics
13.2.2.1 Cellular targeting and tissue tropism
13.2.2.2 Stability and immunogenicity
13.2.2.3 Biodegradability and clearance
13.2.3 Engineering for enhanced delivery
13.2.3.1 Loading of therapeutic payload
13.2.3.2 Modifications for targeting
13.3 Exosomes for gene delivery
13.3.1 Advantages over conventional vectors
13.3.2 Exosome-mediated delivery of mRNA
13.3.3 Exosome-mediated delivery of siRNA/miRNA
13.3.4 Exosome-mediated delivery of CRISPR-Cas9
13.4 Exosomes for vaccination
13.4.1 Interaction with immune system
13.4.2 Inherent immunomodulatory properties
13.4.3 Exosome-based immunization strategies
13.4.3.1 Therapeutic cancer vaccines
13.4.3.2 Viral infectious diseases
13.4.3.3 Non-viral infectious diseases
13.5 Clinical status
13.6 Challenges and future prospects
13.7 Conclusions
Chapter 14. Theranostic potential of exosomes in neurodegenerative diseases
14.1 Introduction
14.1.1 Biogenesis of brain exosomes
14.1.2 Uptake of brain exosomes
14.1.3 Isolation of brain exosomes
14.1.4 Brain exosome composition
14.1.5 Characteristics of exosomes
14.2 Physiological role of exosomes in neurodegenerative diseases
14.2.1 Exosomes in Alzheimer's disease
14.2.2 Exosomes in Parkinson's disease
14.2.3 Exosomes in Huntington's disease (HD)
14.2.4 Exosomes in amyotrophic lateral sclerosis (ALS)
14.3 Therapeutic roles of exosomes in neurodegenerative diseases
14.3.1 Exosomes and Alzheimer's disease
14.3.2 Exosomes and Parkinson disease
14.3.3 Exosomes and Huntington disease
14.3.4 Exosomes and amyotrophic lateral sclerosis (ALS)
14.4 Exosome in diagnosis of neurodegenerative diseases
14.4.1 Exosomes as potential biomarker
14.5 Exosomes application in drug delivery and vaccine
14.5.1 Drug delivery
14.5.2 Vaccination
14.6 Conclusion and perspective
Chapter 15. Exosomes in cancer therapeutic delivery
15.1 Introduction
15.1.1 Carcinoma
15.1.2 Sarcoma
15.1.3 Leukemia
15.1.4 Melanoma
15.1.5 Lymphoma
15.2 Role of exosomes in diagnosis and treatment of cancer
15.3 Exosomes in different types of cancer
15.3.1 Exosomes in breast cancer
15.3.2 Exosomes in lung cancer
15.3.3 Exosomes in colorectal cancer
15.3.4 Exosomes in prostate cancer
15.3.5 Exosomes in ovarian cancer
15.3.6 Exosomes in brain cancer
15.3.7 Exosomes in oral cancer
15.3.8 Exosomes in hepatic cancer
15.3.9 Exosomes in leukemia
15.4 Conclusion
Chapter 16. Potential role of parasite-derived exosomes in human diseases
16.1 Introduction
16.2 EVs and parasitic protozoa
16.2.1 Malaria
16.2.1.1 The life cycle of Plasmodium
16.2.1.2 The role of EVs in malaria
16.2.2 Visceral leishmaniasis
16.2.3 Trypanosomiasis
16.2.4 Toxoplasmosis
16.3 The therapeutic potential of EVs in parasitic diseases
16.4 Conclusion
Chapter 17. Current applications of new generations of exosomes nanovesicles
17.1 Introduction
17.2 Methods for EXOs engineering
17.2.1 Loading EXOs with therapeutic cargo
17.2.2 Surface modification of EXOs
17.2.3 Isolation and purification techniques
17.2.4 Microfluidics and nanotechnology
17.2.5 Quality control and characterization
17.3 EXOs in cardiovascular diseases: Cardioprotection and vascular health
17.3.1 EXOs and cardio protection
17.3.2 EXOs in vascular health
17.4 EXOs in regenerative medicine: Tissue engineering and wound healing
17.4.1 Tissue engineering
17.4.2 Wound healing
17.5 Emerging trends and future perspective
17.5.1 Diagnostic biomarkers
17.5.2 Therapeutic applications
17.5.3 Precision medicine
17.5.4 Neurodegenerative diseases
17.5.5 Immunomodulation
17.5.6 Standardization in isolation and characterization
17.5.7 EXO engineering advancements
17.5.8 Clinical translation
17.5.9 Biomimetic nanotechnology
17.6 Conclusion
Chapter 18. Clinical trials and translational research in exosome nanovesicle therapeutics
18.1 Introduction
18.2 Exosome nanovesicle
18.2.1 Structural characteristics and exosome biogenesis
18.2.2 Biological functions and diagnostic markers and therapeutics delivery vehicle
18.3 Translational research—Exosome therapeutics
18.3.1 Preclinical studies-exosome therapeutics
18.3.1.1 Cancer studies
18.3.1.2 Neurological diseases
18.3.1.3 Immunological disease
18.3.1.4 Others
18.3.2 Clinical trials-exosome therapeutics
18.3.2.1 Cancer studies
18.3.2.2 Neurological and psychiatric diseases
18.3.2.3 Immunological diseases
18.3.2.4 Others
18.4 Translational findings into clinical practice and future directions
18.5 Conclusion
Chapter 19. Scale-up and manufacturing of exosome-based therapeutics
19.1 Introduction
19.2 Need for exosomes scale-up
19.2.1 Exosomes exhibit paracrine effects
19.2.2 Targeted delivery and precision medicine
19.2.3 Biocompatibility and immunomodulatory properties
19.2.4 Delivery system for blood brain barrier
19.2.5 Brain targeting and specificity
19.2.6 Neurological disorders and therapeutic applications
19.2.7 GMP compliant manufacturing methods of exosomes
19.2.8 isolation and purification of exosomes
19.2.9 Cell culture and supernatant collection
19.2.10 Centrifugation for debris removal
19.2.11 Ultracentrifugation for initial pelleting
19.2.12 Ultrafiltration for higher concentration
19.2.13 Size exclusion chromatography
19.2.14 Tangential flow filtration
19.2.14.1 Tangential flow filtration setup and operation
19.2.14.2 Collection of retentate and post-filtration processing
19.2.15 Quality Control and Quality Assurance of exosomes
19.2.16 Quantitative analysis
19.2.17 Purity assessment
19.2.18 Functional validation
19.2.19 Standardization and quality assurance
19.2.20 Regulatory compliance
19.2.21 Storage of exosomes
19.2.22 Temperature control
19.2.23 Avoidance of freeze-thaw cycles
19.2.24 Use of cryoprotectants
19.2.25 Lyophilization (freeze-drying)
19.2.26 Considerations for clinical applications
19.2.27 Optimization and validation
19.3 Conclusion
19.4 Future perspectives
Chapter 20. Regulatory and ethical considerations in exosome-based therapeutics
20.1 Introduction
20.1.1 Overview of exosome-based therapeutics
20.1.2 Difficulties with treatments based on exosomes
20.1.3 Regulatory issues with exosome therapeutics
20.1.4 Importance of regulatory and ethical considerations
20.2 Key considerations for developing exosome-based therapeutics
20.3 Ethical challenges associated with exosome therapy
20.4 Current understanding in regulatory and ethical framework for exosome-based therapeutics
20.4.1 Regulatory landscape
20.4.1.1 Comparison with traditional pharmaceuticals and biologics
20.4.1.2 Existing guidelines and policies
20.4.2 Challenges in regulation
20.4.2.1 Standardization of isolation and characterization methods
20.4.2.2 Quality control and assurance
20.4.2.3 Reproducibility and scalability
20.4.3 Proposed regulatory pathways
20.4.3.1 Frameworks from leading regulatory bodies: FDA and EMA
20.4.3.2 Role of international collaboration and harmonization
20.5 GMP-grade exosome production methods
20.5.1 Purity, potency, and safety
20.5.2 Isolation
20.5.3 Standardization and characterization
20.5.4 Storage and stability
20.5.5 Clinical trials and dosing
20.5.6 Regulatory approval pathways
20.6 Exosome therapeutics: Preclinical and clinical considerations
20.6.1 Preclinical studies
20.6.2 Clinical trials
20.6.3 Dosing
20.6.4 Pharmacokinetics
20.6.5 Regulatory pathways
20.7 Regulatory and ethical issues in exosome therapeutics: Overcoming technical and biological obstacles
20.7.1 Challenges
20.7.2 Regulatory and ethical considerations
20.8 Discussion
20.9 Conclusion
Index

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Exosome Communication

Advances in Research and Therapeutics for Health and Disease

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Dalapathi Gugulothu

Dharmendra Kumar Khatri

Lalitkumar K. Vora

William C.S. Cho

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