Stem Cell Processing (Stem Cells in Clinical Applications)

This invaluable resource delineates procedures for development and use of stem cells in the laboratory and explores the potential for clinical applications. The text discusses mesenchymal stem cell isolation, isolation of adipose derived stem cells, new trends of induced pluripotent stem cells in disease treatment, cord blood banking, future directions of the discussed therapies and much more. The chapters are contributed by preeminent scientists in the field and present a comprehensive picture of stem cell processes, from development in the laboratory to effects and side-effects of clinical application.__Stem Cell Processing__ and the other books in the __St__em Cells in Clinical Applications series, edited by Dr. Phuc Van Pham, is essential reading for scientists, researchers, advanced students and clinicians working in stem cells, regenerative medicine or tissue engineering. Preface 6 Contents 8 Contributors 10 About the Editor 14 Chapter 1: Stem Cell Therapy: Accepted Therapies, Managing the Hope of Society, and a Legal Perspective 15 1.1 Background 15 1.1.1 Basic Principles of Stem Cell Biology 16 1.1.2 Clinical Applications of Stem Cell Therapy 16 1.2 Controversies and the Consequence of Providing Unproven Stem Cell Therapies 17 1.2.1 Reference to Pertinent Issues and Controversial Reports 17 1.2.1.1 According to the Legal Status of the Treatment 19 1.2.1.2 According to Who Is Paying for the Treatment 19 1.2.1.3 According to Where Patients Are Traveling for Treatment 19 1.2.2 Ethical and Legal Concerns 20 1.2.2.1 Sources and Sourcing of Human Stem Cells 20 Moral and Legal Status of an Embryo 20 Embryos Arising from Infertility Treatment 22 Embryos Created Specifically for Research Purposes 22 Sourcing of Oocytes for the Creation of Embryos 22 Cadaveric Fetal Tissue 23 Somatic Cell Nuclear Transfer (SCNT) 24 1.2.2.2 Therapeutic Versus Reproductive Cloning 24 1.2.2.3 Informed Consent in the Context of Embryos or Fetal Tissue 25 1.2.2.4 Clinical Use 26 1.2.3 Impact on Societal Perceptions 26 1.3 Stem Cell Therapy as Biological Medicine 26 1.3.1 Product Categorization and Registration Requirements 26 1.3.2 Minimal Manipulation Requirements 27 1.4 Global Legal Positions 28 1.5 International Harmonization Efforts 33 1.5.1 A Need for Harmonization 33 1.5.2 Consensus Principles 34 1.5.3 Issues of Difference 35 1.5.4 US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) 36 1.5.4.1 FDA-EMA-Health Canada ATMP Cluster 36 1.5.5 International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) 36 1.5.5.1 ICH (Regulators Forum Cell Therapy Group (RFCTG) and Regulators Forum Gene Therapy Group (RFGTG)) 36 1.5.6 International Medical Device Regulators Forum (IMDRF) 37 1.5.7 Asia-Pacific Economic Cooperation/Life Sciences Innovation Forum (APEC/LSIF) 37 1.5.8 Alliance for Harmonization of Cellular Therapy Accreditation (AHCTA) and the Foundation for the Accreditation of Cellular Therapy (FACT) 38 1.5.9 Future Global Regulation 38 1.6 Conclusion 39 References 39 Chapter 2: Mesenchymal Stem Cells in Clinical Applications 50 2.1 Introduction 50 2.2 How MSCs Can Treat Diseases? 51 2.2.1 Tissue Regeneration 54 2.2.2 Immune Modulation 55 2.3 Clinical Applications of MSCs 57 2.3.1 Approved MSC-Based Products 57 2.3.2 Clinical Trials of MSC-Based Therapy 59 2.3.2.1 MSCs for Osteoarthritis 59 2.3.2.2 Cardiovascular Diseases 64 2.3.2.3 MSCs for Chronic Inflammatory and Autoimmune Diseases 64 2.3.2.4 MSCs for Liver, Lung, and Kidney Disease 65 2.3.2.5 Diabetes Mellitus (DM) 66 2.3.2.6 MSCs in Acute Brain Injury: Stroke 67 2.4 Safety of MSCs in Clinical Applications 67 2.5 Conclusions 68 References 71 Chapter 3: Ageing and Senescence in Mesenchymal Stem Cells 83 3.1 Donor age 83 3.2 Senescence 85 3.3 Tactics to Overcome Ageing 86 References 86 Chapter 4: New Trends in Clinical Applications of Induced Pluripotent Stem Cells 88 4.1 History and Generation of iPSCs 88 4.2 Production of iPSCs with Clinical Grade 92 4.2.1 iPSCs Can Be Produced in Clinical Conditions 92 4.2.2 Transferring the Manufacturing Process to the GMP Suite 95 4.2.3 Quality Control Testing During iPSC Production 95 4.3 Applications of iPSCs in Clinic 95 4.3.1 Disease Modeling and Drug Screening 95 4.3.1.1 Disease Modeling 95 4.3.1.2 Drug Screening 96 4.3.2 Regenerative Medicine 98 4.3.2.1 iPSCs and Neural Regenerative Medicine 99 4.3.2.2 iPSCs in Cardiac Regenerative Medicine 100 4.3.2.3 iPSCs in Diabetic Mellitus and Liver Disease 101 4.3.3 Clinical Applications of iPSCs 102 4.4 Conclusions 102 References 103 Chapter 5: The Effects of Ageing on Proliferation Potential, Differentiation Potential and Cell Surface Characterisation of Human Mesenchymal Stem Cells 110 5.1 Introduction 110 5.2 Ageing 111 5.3 Ageing and Proliferation 112 5.4 Ageing and Differentiation Potential 113 5.5 Ageing and Cell Surface Characterisation 114 5.6 Conclusion 115 References 115 Chapter 6: Production of Clinical-Grade Mesenchymal Stem Cells 118 6.1 Introduction 118 6.2 GMP Principles 121 6.3 GMP Facilities for Cellular Products 123 6.4 Regulation of MSC Production 125 6.5 Production Processes for Non-expanded MSCs 126 6.5.1 Isolation of Non-expanded MSCs from Peripheral Blood, Bone Marrow, and Umbilical Cord Blood 126 6.5.2 Isolation of Non-expanded MSCs from Adipose Tissue 127 6.6 Ex Vivo-Expanded MSCs 128 6.6.1 Media 128 6.6.2 Culture Platforms 131 6.6.3 Harvesting Adherent Cells 133 6.6.4 Cryopreservation of Cellular Products 133 6.6.5 Control of MSC Quality and Safety 134 6.6.5.1 MSC Quality Control 134 6.6.5.2 MSC Safety 135 6.7 Conclusion 137 References 137 Chapter 7: Isolation and Characterization of Adipose-­Derived Stromal Cells 141 7.1 Introduction 141 7.2 Isolation Methods 142 7.2.1 Manual Isolation Procedure 143 7.2.1.1 Seeding 143 7.2.1.2 Expansion of ASCs In Vitro 144 Cell Expansion for Research Purposes 145 Xeno- and Serum-Free Cell Expansion for Clinical Application 146 7.2.2 Isolation Using Automated Closed Systems 147 7.3 In Vitro Characterization of ASCs 148 7.3.1 Immunophenotypic Characterization of ASCs 148 7.3.2 In Vitro Differentiation Assessments and Limitations 150 7.3.2.1 Adipogenesis 150 Assessment of Adipogenic Differentiation 153 Quantitative Adipogenesis Assessment Using Oil Red O 153 Quantitative Adipogenesis Assessment Using Nile Red 153 Quantitative Adipogenesis Assessment Using Flow Cytometry 153 7.3.2.2 Osteogenesis 155 7.3.2.3 Chondrogenesis 157 7.3.2.4 Myogenesis 158 7.3.3 Experimental Animal Models 159 7.4 Conclusion 159 Appendix: Brief Description of Current Methods 160 Manual Isolation Procedure 160 Methods Used to Obtain Absolute Cell Counts 162 Trypan Blue (0.4 %) Dye Exclusion Method 162 Absolute Cell Count Determination Using a Benchtop Flow Cytometer (Beckman Coulter Flow Cytometers) 162 Induction of Adipogenesis In Vitro 163 Qualitative Assessment of Adipogenesis In Vitro Using Oil Red O 164 Induction of Osteogenesis In Vitro 165 Qualitative Assessment of Osteogenesis In Vitro 165 Induction of Chondrogenesis In Vitro 165 Qualitative Assessment of Chondrogenesis In Vitro 166 References 166 Chapter 8: Cord Blood Stem Cell Banking 172 8.1 Introduction 173 8.1.1 Umbilical Cord Blood Versus Bone Marrow or Mobilized Stem Cells for Transplantation 173 8.1.2 Umbilical Cord Blood Stem Cell Banks 175 8.1.2.1 Public Cord Blood Banks 175 8.1.2.2 Private Cord Blood Banks 177 8.1.2.3 Hybrid Cord Blood Banks 179 8.1.2.4 Global Policies and Legislation 179 8.1.3 Cord Blood Banking in Developed Versus Developing Countries 180 8.1.4 Cord Blood Stem Cells in Transplantation and Regenerative Medicine 182 8.2 Summary 186 References 186 Chapter 9: Human Embryonic Stem Cells and Associated Clinical Concerns 190 9.1 Introduction 190 9.2 Human ES Cells 191 9.2.1 Sources 191 9.2.2 Isolation 193 9.2.3 Culture 195 9.2.4 Differentiation 196 9.3 Challenges Faced 198 9.3.1 Ethical Dilemma 198 9.3.2 Technical Challenges 198 9.4 Overcoming Challenges 200 9.4.1 Somatic Cell Nuclear Transfer 200 9.4.2 Induced Pluripotent Stem (iPS) Cells 201 9.4.3 Immune Isolation 202 9.4.4 Bioactive Scaffold and Lentivirus 202 9.4.5 Pro-survival Molecules 204 9.5 Conclusion and Future Perspectives 204 References 205 Chapter 10: Harvesting and Collection of Adipose Tissue for the Isolation of Adipose-Derived Stromal/Stem Cells 207 10.1 Introduction 207 10.2 Factors Influencing ASC Characteristics 208 10.2.1 Adipose Tissue Type and Anatomical Location 208 10.2.2 Patient Age and Gender 211 10.2.3 Harvesting Techniques 212 10.2.3.1 Liposuction Versus Biopsy/Resection 212 10.2.3.2 Background on Liposuction 214 10.2.3.3 Suggested ASC Harvesting Technique 216 10.2.4 Factors Influencing ASC Isolation and Expansion 219 10.3 Conclusion 223 References 224 Index 229 Front Matter....Pages i-xiii Stem Cell Therapy: Accepted Therapies, Managing the Hope of Society, and a Legal Perspective....Pages 1-35 Mesenchymal Stem Cells in Clinical Applications....Pages 37-69 Ageing and Senescence in Mesenchymal Stem Cells....Pages 71-75 New Trends in Clinical Applications of Induced Pluripotent Stem Cells....Pages 77-98 The Effects of Ageing on Proliferation Potential, Differentiation Potential and Cell Surface Characterisation of Human Mesenchymal Stem Cells....Pages 99-106 Production of Clinical-Grade Mesenchymal Stem Cells....Pages 107-129 Isolation and Characterization of Adipose-Derived Stromal Cells....Pages 131-161 Cord Blood Stem Cell Banking....Pages 163-180 Human Embryonic Stem Cells and Associated Clinical Concerns....Pages 181-197 Harvesting and Collection of Adipose Tissue for the Isolation of Adipose-Derived Stromal/Stem Cells....Pages 199-220 Back Matter....Pages 221-225 "This invaluable resource delineates procedures for development and use of stem cells in the laboratory and explores the potential for clinical applications. The text discusses mesenchymal stem cell isolation, isolation of adipose derived stem cells, new trends of induced pluripotent stem cells in disease treatment, cord blood banking, future directions of the discussed therapies and much more. The chapters are contributed by preeminent scientists in the field and present a comprehensive picture of stem cell processes, from development in the laboratory to effects and side-effects of clinical application. Stem Cell Processing and the other books in the Stem Cells in Clinical Applications series, edited by Dr. Phuc Van Pham, is essential reading for scientists, researchers, advanced students and clinicians working in stem cells, regenerative medicine or tissue engineering."--Publisher This invaluable resource delineates procedures for development and use of stem cells in the laboratory and explores the potential for clinical applications. The text discusses mesenchymal stem cell isolation, isolation of adipose derived stem cells, new trends of induced pluripotent stem cells in disease treatment, cord blood banking, future directions of the discussed therapies and much more. The chapters are contributed by preeminent scientists in the field and present a comprehensive picture of stem cell processes, from development in the laboratory to effects and side-effects of clinical application. Stem Cell Processing and the other books in the St em Cells in Clinical Applications series, edited by Dr. Phuc Van Pham, is essential reading for scientists, researchers, advanced students and clinicians working in stem cells, regenerative medicine or tissue engineering.