Unique resource focusing on biomedical applications and clinical translation of extracellular vesicles in science and medicine

Focusing on key points to better understand extracellular vesicles (EVs) and their development, Biomedical Applications of Extracellular Vesicles describes in detail the biogenesis of EVs, the mechanism of intercellular communication, and the treatment of various diseases of EVs and the EV-based drug delivery platforms. An application-oriented resource, the work presents rapidly newer biomedical and clinical applications of natural and engineered EVs such as drug delivery, diagnosis, prognosis monitoring, immunotherapy, and more.

The first part of this book provides a basic background on EVs. Next, the book introduces the excellent therapeutic effects of EVs themselves and the underlying mechanisms, followed by how EVs from different sources were used to construct drug delivery platforms. The latest research on EVs from leading groups around the world is presented.

Sample topics covered in Biomedical Applications of Extracellular Vesicles include:

• Biogenesis of various EVs
• Pros and cons of the different instrumental and methodological developments for analytical strategies applied to EVs
• EVs in treatment of major diseases, such as cancer, cardiovascular and respiratory diseases
• Current methods of engineering EVs, and a comparison of the advantages and disadvantages of each method
• Biomaterials, such as hydrogels, scaffolds, and microneedles, that have been developed to further enhance the therapeutic efficacy of EVs
• Key challenges, such as quality control, scalability, and biosafety, that limit the clinical and industrial translation of EVs

Explaining in detail how extracellular vesicles are produced and engineered, along with potential applications and commercial developments of EVs in science and industry, Biomedical Applications of Extracellular Vesicles is an essential resource on the subject for chemists, cell biologists, and molecular physicists.

Preface xi

1 Extracellular Vesicles and Their Biomedical Applications: An Overview 1
Xing-Jie liang, Ke Cheng, and Zhenhua li

1.1 Introduction 1

1.2 Biogenesis and Composition of Extracellular Vesicles 1

1.3 Biological Functions of Extracellular Vesicles 2

1.4 Extracellular Vesicles Isolation and Limitations 3

2 Biogenesis and Identification of Extracellular Vesicles 5
Dandan Ding, Xing Zhang, Yu Zhao, Xiaoya Li, Qingqing Leng, and Zhenhua li

2.1 Biogenesis of Extracellular Vesicles 5

2.1.1 Biogenesis of Exosome 6

2.1.2 Biogenesis of Microvesicle 8

2.1.3 Biogenesis of Apoptotic Bodies 8

2.1.4 Biogenesis of Large Oncosomes 9

2.2 Identification of Extracellular Vesicles 9

2.2.1 Electron Microscopic Identification 9

2.2.1.1 Scanning Electron Microscopy 9

2.2.1.2 Transmission Electron Microscopy 10

2.2.1.3 Atomic Force Microscopy 11

2.2.1.4 Cryo-Electron Microscopy 12

2.2.2 Particle Size Detection 13

2.2.2.1 Nanoparticle Tracking Analysis 13

2.2.2.2 Dynamic Light Scattering 14

2.2.3 Surface Protein Assay 16

2.2.3.1 Protein Immunoblotting Method 17

2.2.3.2 Nano-Flow Cytometry 19

2.2.3.3 Enzyme-Linked Immunosorbent Assay 19

2.2.4 Other Methods 21

2.2.4.1 Tunable Resistive Pulse Sensing 21

2.2.4.2 Single EV Analysis Technique 22

2.2.4.3 Micronuclear Magnetic Resonance 23

References 24

3 Therapeutic Potential of Extracellular Vesicles from Different Cell Sources 35
Xueyi Wang and Zhenhua li

3.1 Extracellular Vesicles Derived from Stem Cells (SCs) 35

3.1.1 Extracellular Vesicles Derived from Mesenchymal Stem Cells (MSCs) 37

3.1.1.1 Kidney Injury 38

3.1.1.2 Myocardial Ischemia/Reperfusion Injury (MI/RI) 38

3.1.1.3 Spinal Cord Injury (SCI) 39

3.1.1.4 Cancer 40

3.1.2 Extracellular Vesicles Derived from Neural Stem Cells (NSCs) 40

3.1.3 Extracellular Vesicles Derived from Endothelial Progenitor Cells (EPCs) 41

3.1.4 Extracellular Vesicles Derived from Cardiac Progenitor Cells (CPCs) and Other Stem Cells 41

3.2 Extracellular Vesicles Derived from Immune Cells 42

3.2.1 Extracellular Vesicles Derived from Macrophages 42

3.2.2 Extracellular Vesicles Derived from Dendritic Cells (DCs) 44

3.2.3 Extracellular Vesicles Derived from T Cells 45

3.2.4 Extracellular Vesicles Derived from Natural Killer (NK) Cells 46

3.3 Extracellular Vesicles Derived from Cancer Cells 47

3.4 Extracellular Vesicles Derived from Plants 49

3.4.1 Anti-inflammatory 49

3.4.2 Anticancer 50

3.4.3 Antibacterial 51

3.4.4 Antioxidation 51

References 51

4 Biomedical Applications of Extracellular Vesicles in Treatment of Disease 59
Fei Wang, Jiacong Ai, Ziyang Zhang, Yuanhang li, and Zhenhua li

4.1 Tissue Engineering and Regenerative Medicine 60

4.2 Metabolic Diseases 67

4.3 Cardiovascular Diseases 74

4.4 Respiratory Diseases 85

4.5 Cancers 88

4.6 Conclusion and Perspectives 93

References 94

5 Applications of Engineered Extracellular Vesicles 101
Lanya li, Yingxian Xiao, Shushan Mo, and Zhenhua li

5.1 Engineering EVs for Cargo Loading 101

5.1.1 Endogenous Loading 101

5.1.2 Exogenous Loading 104

5.2 Engineering EVs for Surface Modification 106

5.2.1 Genetic Engineering 106

5.2.2 Chemical Modification 108

5.2.3 Hydrophobic Membrane Engineering 109

References 111

6 Current Technology for Production, Isolation, and Quality Control of Extracellular Vesicles 117
Dandan Han, Yichuan Ma, Yujing Hu, and Zhenhua li

6.1 Production of EVs 117

6.1.1 Three-Dimensional Culture 117

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