Preface
Acknowledgements
Contents
About the Editor
1: Stem Cell Therapy: Significance and Applications of Stem Cell Products in Tissue Engineering and Regenerative Medicine
1.1 Tissue Engineering and Regenerative Medicine (TERM)
1.2 Biomaterial Scaffolds as Essential Factors for the Success of TERM
1.3 Stem Cells and Their Products as Essential Factors for the Success of TERM
1.4 Clinical Application of Stem Cells Therapy in TERM
1.4.1 Cardiovascular System
1.4.2 Lungs
1.4.3 Nerves
1.4.4 Bone
1.4.5 Cartilage
1.4.6 Tendon/Ligaments
1.4.7 Liver
1.4.8 Urinary System
1.4.9 Cornea
1.4.10 Skin
1.5 Future Perspective of Stem Cells and Their Products in TERM
References
2: GLP Requirements of Stem Cells
2.1 Laboratory Design
2.1.1 Key Consideration in Planning and Design
2.1.1.1 Budget
2.1.1.2 Space
2.1.1.3 Type and Scope of Work
Biosafety Requirement for Tissue Culture Labs
2.1.1.4 Major Equipment
2.2 Major Functional Areas
2.2.1 Tissue Culture Laboratory
2.2.2 Quarantine Laboratory
2.2.3 Quality Control Laboratory
2.2.4 Microscopy Laboratory
2.3 Personnel
2.4 Freezer Rooms
2.5 Storage Areas
2.6 Information Technology
2.7 Key Construction Considerations
2.7.1 Engineering Controls
2.7.2 HVAC
2.7.3 Electrical Capacity and Routing
2.7.4 Interior Finishes
2.7.5 Tissue Culture Area
2.7.6 Quality Control Laboratory
2.7.7 Quarantine Laboratory
2.7.8 Storage
2.8 Equipment
2.8.1 Tissue Culture Laboratory
2.8.2 Biosafety Cabinets
2.8.3 CO2 Incubators
2.8.4 Pipettes
2.8.5 Vacuum Flask
2.8.6 Water Bath
2.8.7 Low Speed Centrifuge
2.8.8 Microscopy
2.8.8.1 Phase Contrast Microscope
2.8.8.2 Dissecting Microscope
2.8.9 Storage
2.8.10 Quality Control Laboratory
2.8.10.1 RT-PCR
2.8.10.2 Flow Cytometer
2.8.10.3 Fluorescent Microscope
2.8.10.4 Confocal Microscope
2.8.11 Quarantine Laboratory
2.8.11.1 Class II Biosafety Cabinet
2.8.11.2 CO2 Incubator
2.8.11.3 Phase Contrast Microscope
2.8.11.4 Water Bath
2.8.11.5 Low Speed Centrifuge
2.8.11.6 Pipettes
2.8.11.7 Aspiration/Vacuum Flask
2.9 Quality Control
2.9.1 Reliable Techniques
2.9.2 Validated Reagents
2.9.3 Quality PSCs
2.9.4 Checklist for Confirming Quality
2.10 Approvals
2.10.1 Typical Institutional Review
2.10.1.1 Stem Cell Research Oversight Committee (SCRO)
2.10.1.2 Institutional Review Board (IRB)
2.10.1.3 Biosafety Committee Review (IBC)
2.10.1.4 Institutional Animal Committee (IACUC)
References
3: Current Good Manufacturing Practice (cGMP) Facility and Production of Stem Cell
3.1 General Regulation for CGTP
3.2 What Is cGMP?
3.2.1 Primary Aspect in cGMP
3.3 Quality Management System in Good Manufacturing Practice
3.4 Quality System
3.5 Quality Assurance and Quality Control
3.6 Document Preparation and Control
3.7 Facility Design and Construction
3.8 Facility Management
3.9 Environmental Control and Monitoring
3.10 Equipment and Maintenance in cGMP Facility
3.11 Calibration and Performance Check Procedures
3.12 Process, Personnel and Waste Flow
3.13 Cleaning
3.14 Quality Control Requirement for Stem Cell Therapy Products
3.15 Selection of Critical Material
3.15.1 Selection and Evaluation of Donor Suitability
3.15.2 Raw Materials Qualification
3.15.3 Master Cells Stock
3.16 Production Protocol
3.17 Validation
3.18 Process Validation
3.18.1 Media Fill Validation
3.18.2 Material Validation/Use Test
3.18.3 Dry Run
3.19 Equipment and Facility Validation
3.20 Quality Control Testing and Release of the MSCs
3.21 Personnel Training and Competency
3.22 Regulatory Requirement Process
3.23 Ethics, Legal and Social Issues in Stem Cell Research
3.24 Unapproved Stem Cell Therapy
3.25 Risk, Limitation and Adverse Effects Associated with Stem Cell Therapy
3.26 Conclusion and the Way Forward
References
4: Global Regulatory Frameworks and Quality Standards for Stem Cells Therapy and Regenerative Medicines
4.1 Introduction
4.2 International Regulatory Framework for Stem Cell and Regenerative Medicine
4.2.1 Europe
4.3 India
4.4 ChinaΒ΄s Rules
4.5 Africa
4.6 United States of America
4.6.1 Regenerative Therapy Guidelines
4.6.2 FDA Ends Their Discretionary Period and Is Focusing on Unscrupulous Providers
4.6.3 Risk-Based Regulatory Tiers for Regenerative Therapies
4.6.4 Lowest-Tier Products
4.6.5 Middle-Tier Products
4.6.6 Minimal Manipulation
4.6.7 Structural Versus Non-structural Cells, Tissues
4.6.7.1 Homologous Use
4.6.8 Highest-Tier Products
4.6.9 Opinion of Stakeholders About FDA Framework
4.7 Japan
4.8 Korea, South
4.8.1 South Korea Released New Law on Advanced Regenerative Medicine and Advanced Biopharmaceuticals
4.9 Australia
4.9.1 Access to the Provision of Cell Treatment to Patients
4.9.2 Reporting Adverse Events
4.9.3 Important Risks to Consider
4.9.4 Advertising
4.9.5 Other Regulatory Oversight
4.10 Canada
4.11 United Arab Emirates
4.12 Kingdom of Saudi Arabia
4.13 Israel
4.14 Quality Standards for Regenerative Medicine
4.15 Conclusion
References
5: Stem Cell Bioreactors: Design, Structure, and Operation of Stem Cell Bioreactors
5.1 Introduction
5.2 Bioreactors and Its Application
5.3 Types of Bioreactors
5.3.1 Continuous Stirred Tank Bioreactors
5.3.2 Bubble Column Bioreactors
5.3.3 Airlift Bioreactors
5.3.4 Fluidized Bed Bioreactors
5.3.5 Packed Bed Bioreactors
5.3.6 Photo-Bioreactors
5.4 Design of Bioreactors
5.5 Function and Operation of Bioreactors
5.5.1 Culture Condition
5.5.2 Temperature Monitoring During Culture
5.5.3 pH Monitoring During Culture
5.5.4 Addition of Nutrients During Culture
5.5.5 Providing Air During Culture
5.5.6 Monitoring Pressure During Culture
5.6 Application of Bioreactors in Stem Cells Production
5.6.1 Induced Pluripotent Stem Cell Expansion
5.7 Future Prospects in the Advances of Bioreactors
References
6: Stem Cell Production: Processes, Practices, and Regulation
6.1 Introduction
6.2 Types of Cell Used as Cell Therapy Medicinal Products: An Overview
6.2.1 Immune Cells
6.2.2 Cells for Regenerative Medicine
6.2.3 Cell Types for Different Approaches
6.3 Cell Sources
6.4 Cell Culture and Expansion
6.4.1 Cell Isolation and Purification Methods
6.4.2 Isolation of MSCs
6.4.3 Limbal Stem Cells Isolation
6.4.4 Treg Isolation
6.4.5 MPhis Isolation
6.4.6 iPSCs Isolation
6.5 Culture Media
6.6 Cell Expansion, Activation, and Differentiation
6.6.1 Immune Cells
6.6.2 Cells for Regenerative Medicine
6.7 Closed Culture Systems
6.8 Cryopreservation
6.9 Conclusions
References
7: Upscaling of Clinical Grade Stem Cell Production: Upstream Processing (USP) and Downstream Processing (DSP) Operations of C...
7.1 Introduction
7.2 Background
7.2.1 Atomic to Organismic Level
7.2.2 Stem Cell Production
7.2.2.1 Categories of Stem Cells
7.2.2.2 Main Sources of Stem Cells
7.3 Upscaling of Clinical Grade Stem Cell Production
7.4 Upstream Processing (USP) Operations of Cell Expansion
7.4.1 Upstream Processing Areas, Systems, and Equipment
7.4.2 Clean in Place and Steam in Place Systems
7.4.3 Cell Isolation and Cell Culture
7.4.4 Cell Proliferation and Expression
7.4.5 Cell Banking
7.5 Downstream Processing (DSP) Operations of Cell Expansion
7.6 Harvest
7.7 Detachment
7.8 Separation
7.9 Washing and Concentration Steps
7.10 Regulatory Requirements
References
8: Characterization of Clinical-Grade Stem Cells: Microscopic, Cellular, Molecular, and Functional Characterization of Stem Ce...
8.1 FDA Regulations and Recommendations for Cell Therapy Product Characterization
8.2 Characterization Strategies for Cell Therapy Products
8.2.1 Identity
8.2.2 Potency Assays
8.2.3 Reference Materials and Controls
8.2.4 Genome Stability
8.3 Mesenchymal Stem Cell Characterization
8.3.1 Identity
8.3.1.1 Morphology
8.3.1.2 Molecular Markers
8.3.1.3 Multilineage Differentiation
8.3.2 Purity
8.3.3 Viability
8.3.4 Proliferation
8.3.5 Potency
8.3.5.1 Immunoactivity
8.3.5.2 Angiogenic Assays
8.4 Human Pluripotent Stem Cell Characterization
8.4.1 Identity
8.4.1.1 Morphology
8.4.1.2 Molecular Markers
8.4.1.3 Multilineage Differentiation
8.4.2 Viability
8.4.3 Proliferation
8.4.4 Potency
8.5 Neural Stem Cell Characterization
8.5.1 Identity
8.5.1.1 Morphology
8.5.1.2 Molecular Markers
8.5.1.3 Multilineage Differentiation
8.5.2 Viability
8.5.3 Proliferation
8.5.4 Potency
8.6 Hematopoietic Stem Cell Characterization
8.6.1 Identity
8.6.1.1 Morphology
8.6.1.2 Molecular Markers
8.6.2 HLA Typing
8.6.3 Viability
8.6.4 Colony-Forming Cell Assays
References
9: Stem Cell Safety and Sterility Testing: A Promising Approach in Regenerative Medicine
9.1 Introduction
9.1.1 Stem Cells
9.2 Stem Cells as Therapeutic Agents
9.3 Types of Stem Cells for Tissue Regeneration
9.4 Impediments and Ethical Concerns with Stem Cell-Based Therapies: How to Perpetuate Stem Cells Safety and Sterility
9.5 Stem Cells Safety
9.5.1 Types and Sources of Contamination and Their Characteristics
9.5.2 Microbial and Viral Contamination: Methods for Detection and Eradication
9.6 Sterility in Stem Cell Culture
9.6.1 Tests and Guidelines for Sterility Testing
9.7 Impact of Contamination in Cell
9.8 Methods to Maintain Sterility
9.9 Conclusion
References
10: Stem Cells Storage, Packaging, and Transportation
10.1 Introduction
10.2 Classification of Stem Cells
10.3 Storage and Biopreservation of Stem Cells
10.3.1 Cryopreservation
10.3.2 Chilled Storage
10.3.3 Ambient Temperature Pausing
10.4 Stem Cell Transportation and Packaging
10.5 Cryopreservation
10.5.1 Advantage
10.5.2 Disadvantage
10.5.3 Demand
10.6 Chilled Storage
10.6.1 Advantage
10.6.2 Disadvantage
10.6.3 Demand
10.7 Ambient Temperature Pausing
10.7.1 Advantage
10.7.2 Disadvantage
10.7.3 Demand
10.8 Prospects
10.9 Challenges
References
11: Stem Cell Clinical Trials and Stem Cell Market
11.1 Introduction
11.2 Haematopoietic Stem Cells
11.3 Mesenchymal Stem Cells (MSC)
11.4 Limbal Stem Cells (LSC)
11.5 Neural Stem Cells
11.6 Stem Cell Clinical Trials for Diverse Indications
11.7 Cancer
11.8 Clinical Trials in Heart Diseases
11.9 Clinical Trials to Treat Neurodegenerative Diseases
11.10 Clinical Trials in Spinal Cord Injury
11.11 Clinical Trials in Cerebral Palsy
11.12 Clinical Trials of Stem Cells for Treatment of Diabetes
11.13 Clinical Trials of Stem Cells for Treatment of Eye Disorders
11.14 Clinical Trials of Stem Cells for Infectious Diseases
11.15 Challenges of Stem Cell Clinical Trials and Therapy
11.16 Stem Cell Market
References