Biomedical Applications of Extracellular Vesicles

Dr. Zhenhua Li is Professor at Southern Medical University, China. He serves as an editorial board member of Extracellular Vesicle, Exploration, Materials Today Bio.Dr. Xing-Jie Liang is Deputy Director of Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences.Dr. Ke Cheng is a Professor of Biomedical Engineering at Columbia University.

• Preface xi1 Extracellular Vesicles and Their Biomedical Applications: An Overview 1Xing-Jie liang, Ke Cheng, and Zhenhua li1.1 Introduction 11.2 Biogenesis and Composition of Extracellular Vesicles 11.3 Biological Functions of Extracellular Vesicles 21.4 Extracellular Vesicles Isolation and Limitations 32 Biogenesis and Identification of Extracellular Vesicles 5Dandan Ding, Xing Zhang, Yu Zhao, Xiaoya Li, Qingqing Leng, and Zhenhua li2.1 Biogenesis of Extracellular Vesicles 52.1.1 Biogenesis of Exosome 62.1.2 Biogenesis of Microvesicle 82.1.3 Biogenesis of Apoptotic Bodies 82.1.4 Biogenesis of Large Oncosomes 92.2 Identification of Extracellular Vesicles 92.2.1 Electron Microscopic Identification 92.2.1.1 Scanning Electron Microscopy 92.2.1.2 Transmission Electron Microscopy 102.2.1.3 Atomic Force Microscopy 112.2.1.4 Cryo-Electron Microscopy 122.2.2 Particle Size Detection 132.2.2.1 Nanoparticle Tracking Analysis 132.2.2.2 Dynamic Light Scattering 142.2.3 Surface Protein Assay 162.2.3.1 Protein Immunoblotting Method 172.2.3.2 Nano-Flow Cytometry 192.2.3.3 Enzyme-Linked Immunosorbent Assay 192.2.4 Other Methods 212.2.4.1 Tunable Resistive Pulse Sensing 212.2.4.2 Single EV Analysis Technique 222.2.4.3 Micronuclear Magnetic Resonance 23References 243 Therapeutic Potential of Extracellular Vesicles from Different Cell Sources 35Xueyi Wang and Zhenhua li3.1 Extracellular Vesicles Derived from Stem Cells (SCs) 353.1.1 Extracellular Vesicles Derived from Mesenchymal Stem Cells (MSCs) 373.1.1.1 Kidney Injury 383.1.1.2 Myocardial Ischemia/Reperfusion Injury (MI/RI) 383.1.1.3 Spinal Cord Injury (SCI) 393.1.1.4 Cancer 403.1.2 Extracellular Vesicles Derived from Neural Stem Cells (NSCs) 403.1.3 Extracellular Vesicles Derived from Endothelial Progenitor Cells (EPCs) 413.1.4 Extracellular Vesicles Derived from Cardiac Progenitor Cells (CPCs) and Other Stem Cells 413.2 Extracellular Vesicles Derived from Immune Cells 423.2.1 Extracellular Vesicles Derived from Macrophages 423.2.2 Extracellular Vesicles Derived from Dendritic Cells (DCs) 443.2.3 Extracellular Vesicles Derived from T Cells 453.2.4 Extracellular Vesicles Derived from Natural Killer (NK) Cells 463.3 Extracellular Vesicles Derived from Cancer Cells 473.4 Extracellular Vesicles Derived from Plants 493.4.1 Anti-inflammatory 493.4.2 Anticancer 503.4.3 Antibacterial 513.4.4 Antioxidation 51References 514 Biomedical Applications of Extracellular Vesicles in Treatment of Disease 59Fei Wang, Jiacong Ai, Ziyang Zhang, Yuanhang li, and Zhenhua li4.1 Tissue Engineering and Regenerative Medicine 604.2 Metabolic Diseases 674.3 Cardiovascular Diseases 744.4 Respiratory Diseases 854.5 Cancers 884.6 Conclusion and Perspectives 93References 945 Applications of Engineered Extracellular Vesicles 101Lanya li, Yingxian Xiao, Shushan Mo, and Zhenhua li5.1 Engineering EVs for Cargo Loading 1015.1.1 Endogenous Loading 1015.1.2 Exogenous Loading 1045.2 Engineering EVs for Surface Modification 1065.2.1 Genetic Engineering 1065.2.2 Chemical Modification 1085.2.3 Hydrophobic Membrane Engineering 109References 1116 Current Technology for Production, Isolation, and Quality Control of Extracellular Vesicles 117Dandan Han, Yichuan Ma, Yujing Hu, and Zhenhua li6.1 Production of EVs 1176.1.1 Three-Dimensional Culture 1176.1.2 Physical Stimulation 1196.1.3 Chemical Stimulation 1206.1.4 Physiological Modification 1206.1.5 Genetic Manipulation 1216.2 Extraction of EVs 1226.2.1 Separation Strategies of EVs 1236.2.2 Ultracentrifugation Approach 1236.2.2.1 Differential Ultracentrifugation 1236.2.2.2 Isopycnic and Moving-Zone Density Gradient Ultracentrifugation 1256.2.3 Ultrafiltration Approach 1256.2.4 Size-Exclusion Chromatography 1276.2.5 Polymer Precipitation Strategy 1286.2.6 Immunoaffinity Capture Approach 1286.2.7 Microfluidic Technology 1296.2.8 Other Methods 1316.3 Quality Control of EVs 1326.3.1 Transmission Electron Microscopy 1336.3.2 High-Resolution Liquid Chromatography–Mass Spectrometry 1346.3.3 Enzyme-Linked Immunosorbent Assay 1346.3.4 Fourier-Transform Infrared Attenuated Total Reflection Spectroscopy 1356.3.5 Capillary Electrophoresis 1356.3.6 Nanoparticles Tracking Analysis 1366.3.7 Flow Cytometer 1376.3.8 Other Techniques 138References 1407 Prospects and Limitations of Clinical Application of Extracellular Vesicles 147li Luo, Weirun li, and Zhenhua li7.1 Application of Exosomes as Liquid Biopsy in Clinical Diagnosis 1477.2 Exosomes—It has Become a Star Molecule in Disease Diagnosis 1477.2.1 Exosomes Could Be Used as Prognostic and Diagnostic Biomarkers in Cancer 1507.2.2 Exosomes Biopsy Strategies were Proposed to Target the Different Cancers 1527.2.2.1 Pancreatic Cancer 1527.2.2.2 Gastric Cancer 1527.2.2.3 Lung Cancer 1527.2.2.4 Breast Cancer 1537.2.2.5 Liver Cancer 1537.2.2.6 Ovarian Cancer 1537.2.2.7 Melanoma 1547.2.2.8 Colon Cancer 1547.2.2.9 Glioma 1557.2.3 Exosomes in Clinical Trial for Cancer Biopsy 1557.3 The Commercial Application of Exosomes 1587.3.1 Tumor Therapy 1587.3.2 Lung Infection and ARDS Treatment 1587.3.3 Cardiovascular Disease Treatment 1607.3.4 Liver and Kidney Injury Treatment 1607.3.5 Ophthalmology Treatment 1607.3.6 Cartilage Injury Treatment 1617.3.7 Other Treatments 1617.3.8 Engineering of Exosome Delivery 1617.3.9 Skin Repair and Medical Skincare Products 1647.4 Commercial Development of Exosomes 1667.4.1 Analysis of Representative Companies of Exosomes 1687.4.1.1 ExoCoBio 1687.4.1.2 Direct Biologics 1687.4.1.3 Tianjin Exocrine Science and Technology 1697.4.1.4 TheraXyte 1707.4.1.5 Exosome Diagnostics 1707.4.1.6 Codiak 1717.4.1.7 Evox 1717.4.1.8 EVerZom 1717.5 Issues and Challenges 1727.5.1 Quality Control 1727.5.2 Storage Stability 1727.5.3 Product Safety 1737.5.4 Drug-Forming Properties of Engineered Exosomes 173References 1748 Conclusion and Future Perspectives 181Xing-Jie liang, Ke Cheng, and Zhenhua li8.1 Summary and Conclusions 1818.2 General Trends and Developments 1828.2.1 EVs in Drug Delivery 1828.2.2 Engineered EVs in Biomedical Applications 1838.2.3 EVs for Clinical Applications When Comparing with Liposomes 1848.3 Challenges for Future Research 1858.3.1 Standardization and Quality Control 1858.3.2 Scalability and Manufacturing 1858.3.3 Targeting and Biodistribution 1868.3.4 Safety and Toxicity 1868.3.5 Regulatory Challenges 1868.3.6 Heterogeneity of EV Populations 1878.3.7 Understanding the Role of EVs in Disease Progression and Development 187Index 189