Stem Cell Manufacturing

 
 
Elsevier (Verlag)
  • 1. Auflage
  • |
  • erschienen am 24. Juli 2016
  • |
  • 340 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
E-Book | PDF mit Adobe DRM | Systemvoraussetzungen
978-0-444-63266-1 (ISBN)
 

Stem Cell Manufacturing discusses the required technologies that enable the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic environment as therapeutics, while concurrently achieving control, reproducibility, automation, validation, and safety of the process and the product.

The advent of stem cell research unveiled the therapeutic potential of stem cells and their derivatives and increased the awareness of the public and scientific community for the topic. The successful manufacturing of stem cells and their derivatives is expected to have a positive impact in the society since it will contribute to widen the offer of therapeutic solutions to the patients. Fully defined cellular products can be used to restore the structure and function of damaged tissues and organs and to develop stem cell-based cellular therapies for the treatment of cancer and hematological disorders, autoimmune and other inflammatory diseases and genetic disorders.


  • Presents the first 'Flowchart' of stem cell manufacturing enabling easy understanding of the various processes in a sequential and coherent manner
  • Covers all bioprocess technologies required for the transfer of the bench findings to the clinic including the process components: cell signals, bioreactors, modeling, automation, safety, etc.
  • Presents comprehensive coverage of a true multidisciplinary topic by bringing together specialists in their particular area
  • Provides the basics of the processes and identifies the issues to be resolved for large scale cell culture by the bioengineer
  • Addresses the critical need in bioprocessing for the successful delivery of stem cell technology to the market place by involving professional engineers in sections of the book
  • Englisch
  • Oxford
  • |
  • Niederlande
Elsevier Science
  • 5,49 MB
978-0-444-63266-1 (9780444632661)
0444632662 (0444632662)
weitere Ausgaben werden ermittelt
  • Front Cover
  • STEM CELL MANUFACTURING
  • STEM CELL MANUFACTURING
  • Copyright
  • CONTENTS
  • LIST OF CONTRIBUTORS
  • INTRODUCTION
  • 1 - Genetic Engineering in Stem Cell Biomanufacturing
  • 1.1 INTRODUCTION
  • 1.2 GENETIC MANIPULATION APPROACHES IN HUMAN PLURIPOTENT STEM CELLS
  • 1.2.1 Transgenic Approaches
  • 1.2.2 Knock-In and Knock-Out Approaches
  • 1.2.2.1 Zinc-Finger Nucleases
  • 1.2.2.2 Transcription Activator-Like Effector Nucleases
  • 1.2.2.3 Clustered Regularly Interspaced Short Palindromic Repeat/Cas9
  • 1.2.3 Bacterial Artificial Chromosomes
  • 1.3 APPLICATIONS
  • 1.3.1 Genetic Labeling for Cell Identification and Cell Tracking
  • 1.3.2 Gene Alteration for Directed Differentiation
  • 1.3.3 Gene Disruption for Functional Investigation
  • 1.3.4 Gene Correction for Function Restoration
  • 1.4 DELIVERY METHODS
  • 1.4.1 Transfection
  • 1.4.2 Nucleofection
  • 1.4.3 Viral Transduction
  • 1.5 CONCLUSIONS
  • ACKNOWLEDGMENTS
  • REFERENCES
  • 2 - Biomechanics in Stem Cell Manufacturing
  • 2.1 INTRODUCTION
  • 2.2 CELLULAR BIOMECHANICS
  • 2.2.1 Biomechanical Cues
  • 2.2.2 Shear Forces and Differentiated Cells
  • 2.2.3 Shear Forces and Pluripotent Stem Cells
  • 2.3 SCALE UP TOWARD PRODUCTION-LEVEL BIOREACTORS
  • 2.4 BIOMANUFACTURING CELLS FOR THERAPIES
  • 2.4.1 Pluripotent Stem Cells
  • 2.4.2 Cardiomyocytes
  • 2.4.3 Endothelial Cells
  • 2.5 CONCLUSION
  • REFERENCES
  • 3 - Bioreactor Engineering Fundamentals for Stem Cell Manufacturing
  • 3.1 INTRODUCTION
  • 3.2 STIRRED BIOREACTOR BASICS
  • 3.3 SPECIAL FEATURES OF STIRRED BIOREACTORS FOR HMSC CULTURE ON MICROCARRIERS
  • 3.3.1 Introduction
  • 3.3.2 Preparing the Bioreactor for Culture
  • 3.3.3 Medium and Medium Exchange
  • 3.3.4 Microcarrier Selection
  • 3.3.5 Cell and Microcarrier Concentrations
  • 3.3.6 Attachment Protocol
  • 3.3.7 Use of Coatings to Enhance Attachment
  • 3.3.8 The Minimum Speed for Suspension, NJS and Associated Mean Specific Energy Dissipation Rate, eT¯
  • 3.3.8.1 General Aspects
  • 3.3.8.2 NJS Considerations in hMSC Culture
  • 3.3.9 Oxygen Demand, Mass Transfer, and Optimum Dissolved Oxygen
  • 3.3.9.1 General Considerations
  • 3.3.9.2 Application to hMSC Culture
  • 3.3.10 Fluid Dynamically Generated Stresses and Cell Proliferation
  • 3.3.10.1 General Considerations
  • 3.3.10.2 Application to hMSC Culture
  • 3.3.11 Fluid Dynamically Generated Stresses and Their Application to Cell Harvesting
  • 3.4 FUTURE ISSUES
  • 3.4.1 Increasing Cell Density
  • 3.4.2 Oxygen Demand and Mass Transfer at Higher Cell Density-Sparging and Higher Agitator Speeds
  • 3.4.3 Carbon Dioxide, Osmolality, and pH
  • 3.4.4 Human-Induced and Embryonic Pluripotent Stem Cells
  • 3.5 CONCLUSIONS
  • NOMENCLATURE
  • REFERENCES
  • 4 - Microcarrier Culture Systems for Stem Cell Manufacturing
  • 4.1 OVERVIEW
  • 4.1.1 Historical Perspective
  • 4.2 MICROCARRIER TECHNOLOGY
  • 4.2.1 Types of Microcarriers
  • 4.2.2 Properties of Microcarriers Required for Cell Culturing
  • 4.2.3 Advantages of Using Microcarrier Culture Systems for Cell Manufacturing
  • 4.3 SCALABLE CULTURE SYSTEMS FOR ADHERENT STEM CELLS
  • 4.3.1 Criteria for Microcarrier Selection
  • 4.3.2 Cell Culture Parameters
  • 4.3.2.1 Inoculation Protocol in Microcarriers System
  • 4.3.2.2 Feeding Regime for Cell Production Operation
  • 4.3.2.3 Agitation Influence on Microcarrier-Based Cultures
  • 4.3.2.4 Oxygen Influence on Microcarrier Suspension Systems
  • 4.3.2.5 Cell Harvesting Protocol
  • 4.3.3 Cell Culture Monitoring
  • 4.3.4 Scale-Up of Microcarrier Culture Systems
  • 4.4 MICROCARRIER CULTURE SYSTEMS FOR STEM CELL MANUFACTURING
  • 4.4.1 Mesenchymal Stem/Stromal Cells
  • 4.4.2 Pluripotent Stem Cells
  • 4.5 CONCLUDING REMARKS AND FUTURE PERSPECTIVES
  • LIST OF ABBREVIATIONS
  • REFERENCES
  • 5 - Novel Single-Use Bioreactors for Scale-Up of Anchorage-Dependent Cell Manufacturing for Cell Therapies
  • 5.1 INTRODUCTION
  • 5.2 ANCHORAGE-DEPENDENT CELL CULTURE PROCESSES
  • 5.2.1 Historic Perspective
  • 5.2.2 Monolayer Cultivation on Two-Dimensional Planar Surfaces
  • 5.2.3 3-Dimensional Cell Culture as Aggregates
  • 5.3 CHALLENGES OF ANCHORAGE-DEPENDENT CELL CULTURE PROCESS SCALE-UP
  • 5.3.1 Hydrodynamic Effects on Cells in Microcarrier Cultures
  • 5.3.2 Suspension of Microcarriers
  • 5.3.3 Impact of Suspension Criteria and Microcarrier Concentration
  • 5.4 SINGLE-USE BIOREACTOR PLATFORM FOR CELL THERAPY MANUFACTURING
  • 5.4.1 Single-Use Bioreactor Technology
  • 5.4.2 Key Bioreactor Function Requirements for Cell Therapy Applications
  • 5.4.3 Novel, Vertical-Wheel Bioreactor Platform
  • 5.4.4 Computational Fluid Dynamics
  • 5.4.5 Scalability of Low Shear Mixing in Vertical Wheel Bioreactors
  • 5.5 CELL CULTURE PERFORMANCE OF VERTICAL-WHEEL SINGLE-USE BIOREACTORS
  • 5.5.1 Human Mesenchymal Stromal/Stem Cells
  • 5.5.2 Time-Averaged Flow Fields
  • 5.5.3 Flow Regimes and Scales for Experimentation
  • 5.5.4 A549 Cell Growth and Onco-Ad5 Production
  • 5.6 CONCLUSIONS
  • ACKNOWLEDGMENTS
  • REFERENCES
  • 6 - Bioreactors and Downstream Processing for Stem Cell Manufacturing
  • 6.1 GOOD MANUFACTURING PRACTICE
  • 6.2 PROCESS ANALYTICAL TECHNOLOGY
  • 6.2.1 Ensuring Sterility
  • 6.2.2 Cell Therapy Scale-Up
  • 6.3 BIOREACTOR CULTURE SYSTEMS
  • 6.3.1 Stirred Tank Bioreactors
  • 6.3.2 Bubble Column and Airlift Bioreactors
  • 6.3.3 Fluidized Bed Bioreactor
  • 6.3.4 Packed Bed Bioreactor
  • 6.3.5 Hollow Fiber Bioreactors
  • 6.3.6 Rocking Bag Bioreactor
  • 6.3.7 Planar Bioreactors
  • 6.3.8 Controlled Bioreactor Parameters
  • 6.3.9 Choosing a Bioreactor Culture System
  • 6.3.10 Bioreactor Seed Train
  • 6.3.11 Batch, Fed-Batch, and Perfusion-Mode Cultures
  • 6.3.12 In-Process Controls
  • 6.3.13 Downstream Process in Cell Therapy Manufacturing
  • 6.3.14 Cell Harvesting
  • 6.3.15 Buffer Exchange and Volume Reduction
  • 6.3.16 kSep Technology
  • 6.3.17 Tangential Flow Filtration
  • 6.3.18 Final Formulation
  • 6.3.19 Filling
  • 6.3.20 Final Container
  • 6.3.21 Cryopreservation
  • 6.3.22 Summary
  • REFERENCES
  • 7 - Cell Production System Based on Flexible Modular Platform
  • 7.1 INTRODUCTION
  • 7.2 FEATURES OF THE PROCESS FOR CELL PRODUCTION
  • 7.3 DESIGN FOR CELL PROCESSING
  • 7.4 FLEXIBLE MODULAR PLATFORM TECHNOLOGY
  • ACKNOWLEDGMENTS
  • REFERENCES
  • 8 - Microfluidic Devices for the Culture of Stem Cells
  • 8.1 INTRODUCTION
  • 8.2 DEVICE DESIGN AND FABRICATION
  • 8.2.1 Material Selection and Bonding of Microfluidic Devices
  • 8.2.2 Fluidic Connections
  • 8.2.3 Selection of Fluid Flow Control Method
  • 8.2.4 Temperature Control Methods
  • 8.2.5 Sterilization of Microfluidic Devices
  • 8.2.6 Cell Seeding in Microfluidic Devices
  • 8.3 CONTROL OVER THE MICROENVIRONMENT
  • 8.3.1 Fluid Flow
  • 8.3.2 Mass Transfer Limitations
  • 8.3.3 Controlling Shear Stress
  • 8.3.4 Critical Perfusion Rate
  • 8.4 MONITORING AND CHARACTERIZATION
  • 8.4.1 Optical Detection Methods
  • 8.4.2 Electric Cell-Substrate Impedance Sensing
  • 8.4.3 Light Microscopy Automated with Image Processing
  • 8.5 CONCLUSION AND FUTURE CHALLENGES
  • REFERENCES
  • 9 - Enrichment and Separation Technologies for Stem Cell-Based Therapies
  • 9.1 INTRODUCTION
  • 9.2 ENRICHMENT AND FORMULATION STRATEGIES FOR STEM CELL PRODUCTS CURRENTLY USED IN THE CLINIC
  • 9.2.1 Adult Stem Cells
  • 9.2.2 Pluripotent Stem Cell-Derived Cells
  • 9.3 RECENT ADVANCES IN STEM CELL ENRICHMENT AND SEPARATION
  • 9.3.1 Methods for hPSC Depletion
  • 9.3.1.1 Pluripotent Stem Cell-Cytotoxic Antibodies and Small Molecules
  • 9.3.1.2 Magnetic-Activated Cell Sorting
  • 9.3.1.3 Safety Switches for hPSC Ablation
  • 9.3.2 Methods for Enrichment of hPSC Derivatives
  • 9.3.2.1 Metabolic Signatures and Selection Markers for Cell Enrichment
  • 9.3.2.2 Affinity Chromatography and Aqueous Two-Phase Systems
  • 9.3.2.3 Magnetic Activated Cell Sorting
  • 9.3.2.4 Fluorescence-Activated Cell Sorting
  • 9.4 CONCLUSIONS
  • LIST OF ABBREVIATIONS
  • ACKNOWLEDGMENTS
  • REFERENCES
  • 10 - Expansion and Characterization Considerations for the Manufacturing of Stem Cells
  • 10.1 INTRODUCTION AND POTENTIAL USES AND TARGETS
  • 10.2 MESENCHYMAL STEM/STROMAL CELL ISOLATION, EXPANSION, AND CHARACTERIZATION
  • 10.3 MANUFACTURING WORKFLOW
  • 10.4 IMPORTANCE OF CELL CULTURE MEDIA FOR CELL THERAPY
  • 10.5 PROCESS OPTIMIZATION
  • 10.6 REGULATORY CONSIDERATIONS FOR FILL AND FINISH OF THERAPEUTIC HUMAN STEM CELLS
  • 10.7 CONSIDERATIONS FOR ALTERNATIVE STEM CELL THERAPIES
  • REFERENCES
  • 11 - Storage and Delivery of Stem Cells for Cellular Therapies
  • 11.1 INTRODUCTION
  • 11.1.1 The Role of Business Models for Preservation, Storage, and Delivery
  • 11.2 TYPES OF BIOPRESERVATION
  • 11.2.1 Cryopreservation
  • 11.2.2 Chilled Storage
  • 11.2.3 Ambient Temperature Pausing
  • 11.2.4 Selection of Biopreservation Method
  • 11.3 CHALLENGES IN THE STORAGE AND DELIVERY OF STEM CELLS
  • 11.3.1 Preservation
  • 11.3.1.1 Cryopreservation
  • 11.3.1.2 Chilled
  • 11.3.1.3 Ambient
  • 11.3.2 Understanding the Relevance of Cellular and Therapeutic Quality
  • 11.3.2.1 Defining Product Quality
  • 11.3.2.2 Fresh Versus Frozen
  • 11.3.2.3 Importance of Regulatory Bodies and Guidance
  • 11.3.3 Materials
  • 11.3.3.1 Starting Materials
  • 11.3.3.2 Ancillary and Excipient Materials
  • 11.3.3.3 Packaging
  • 11.3.4 Implementation of Technology During Manufacturing, Distribution, and Final Processing
  • 11.3.4.1 Operating the Process at Scale
  • 11.3.5 Summary
  • 11.4 MITIGATING THE RISKS
  • 11.4.1 Supply Chain Management
  • 11.4.2 A Forward-Looking Strategy
  • 11.5 FUTURE PROSPECTIVE
  • 11.5.1 Cryopreservation and Final Processing
  • 11.5.2 Product Testing
  • 11.5.3 Chains of Custody and Distribution
  • REFERENCES
  • 12 - Business Models for Manufacture of Cellular Therapies
  • 12.1 INTRODUCTION
  • 12.1.1 Definition of Terms
  • 12.1.2 Origins of the Cost of Goods Supplied
  • 12.1.3 The Difference Between Innovation and Research
  • 12.2 THE IMPORTANCE OF BUSINESS MODELS
  • 12.3 BARRIERS TO MARKET ENTRY
  • 12.4 PROFIT AND LOSS
  • 12.5 FACTORS THAT AFFECT THE REVENUE STREAM FOR A CELL-BASED THERAPEUTIC
  • 12.5.1 Capital Outlay
  • 12.5.2 Consumables
  • 12.5.3 Operating Overheads and Indirect Costs of Production
  • 12.5.4 Direct Costs of Production
  • 12.5.5 Reimbursement
  • 12.5.6 Cell-Based Therapeutics and the Cash-Flow Projection
  • 12.6 THE CELL-BASED THERAPEUTIC BUSINESS LANDSCAPE
  • 12.7 A PROPOSED CLASSIFICATION OF BUSINESS MODELS FOR CELL-BASED THERAPEUTICS
  • 12.7.1 Model 1: Metalevel Industry
  • 12.7.2 Model 2: Precompetitive Community
  • 12.7.3 Model 3: Risk Sharing
  • 12.7.4 Model 4: "All You Can Eat"
  • 12.7.5 Model 5: Instantly Available
  • 12.7.6 Model 6: Service Management
  • 12.7.7 Model 7: Franchise
  • 12.8 DISCUSSION
  • 12.8.1 Strengths and Weaknesses of the Models
  • 12.8.2 What Business Models are Currently Strong for Cell-Based Therapeutics?
  • 12.9 CONCLUSION
  • ACKNOWLEDGMENTS
  • REFERENCES
  • 13 - Stem Cells for the Regeneration of Chronic Wounds: A Translational Perspective
  • 13.1 INTRODUCTION
  • 13.2 TYPES AND GENERAL FEATURES OF CHRONIC WOUNDS
  • 13.3 STEM CELLS TO ENHANCE WOUND HEALING: PRECLINICAL STUDIES AND MECHANISMS
  • 13.3.1 Preclinical Studies
  • 13.3.1.1 Human Pluripotent Stem Cells
  • 13.3.1.2 Bone Marrow Cells
  • 13.3.1.3 Hematopoietic Stem Cells
  • 13.3.1.4 Mesenchymal Stem cells (MSCs)
  • 13.3.2 Mechanism
  • 13.4 CLINICAL TRIALS
  • 13.4.1 Bone Marrow Cells
  • 13.4.2 Mesenchymal Stem Cells
  • 13.4.3 Hematopoietic Stem Cells
  • 13.4.4 Human Adipose Stem Cells
  • 13.5 FUTURE PROSPECTS
  • ACKNOWLEDGMENTS
  • REFERENCES
  • INDEX
  • A
  • B
  • C
  • D
  • E
  • F
  • G
  • H
  • I
  • K
  • L
  • M
  • N
  • O
  • P
  • Q
  • R
  • S
  • T
  • U
  • V
  • W
  • X
  • Z
  • Back Cover

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