Cell and Tissue Reaction Engineering

by Eibl, Regine; Eibl, Dieter; Portner, Ralf; Catapano, Gerardo; Czermak, Peter

• ISBN13: 9783642018749
• ISBN10: 3642018742
• Format: Paperback
• Copyright: 2009-08-01
• Publisher: Springer Nature

Summary

Today mammalian cell products, primarily monoclonals, cytokines, recombinant glycoproteins and increasingly vaccines dominate the biopharmaceutical industry. Moreover, a small number of products consisting of in vitro cultivated cells for regenerative medicine have been introduced on the market.This book elucidates the interactions between biological as well as biochemical and engineering principles in processes derived from cell cultures. The authors explain the basic characteristics of mammalian cells related to cultivation systems and the consequences on design and operation of bioreactor systems, so that the importance of cell culture technology as well as differences compared to microbial fermentation technology are understood. Further, special cell culture applications, such as insect cell-based recombinant protein production, bioartificial organs and plant cell-based bioprocessing, are presented.This book is of interest to students of biotechnology as well as scientists and industrial users.

Table of Contents

Mammalian Cells
Mammalian Cell Culture Technology: An Emerging Field	p. 3
Definition and History	p. 3
Fields of Application and Products from Mammalian Cells	p. 6
Future Prospects	p. 8
Exercises	p. 9
References	p. 9
Complementary Reading	p. 11
Characteristics of Mammalian Cells and Requirements for Cultivation	p. 13
Differences Between Mammalian Cells, Plant Cells and Microbes: Consequences of These Differences	p. 13
Types of Mammalian Cells	p. 14
From Primary Cells to Permanent (Established) Cell Lines	p. 15
Hybridom Cells for Production of Monoclonal Antibodies	p. 17
Culture Collections and Cell Banking	p. 20
Culture Media	p. 21
Characteristics of Cell Growth and Metabolism	p. 24
Short Introduction to Cell Metabolism	p. 24
Glucose, Glutamine and Amino Acids as Carbon and Energy Source	p. 26
The Effects of Lactate and Ammonia	p. 29
Oxygen Uptake and Carbon Dioxide Production	p. 31
Kinetic Modelling of Cell Growth and Metabolism	p. 32
Introduction to Kinetic Modelling for Mammalian Cells	p. 32
Set-Up of an Unstructured Model	p. 33
Structured Models	p. 44
Conclusions for Set-Up of a Kinetic Model	p. 45
Questions and Problems	p. 46
List of Symbols	p. 47
References	p. 47
Complementary Reading	p. 53
Bioreactors for Mammalian Cells: General Overview	p. 55
Technical Terminology: Bioreactor/Fermentor, Bioreactor Facility	p. 56
Suitable Bioreactor Types for Mammalian Cell Cultures	p. 57
Categorization, Functional Principle, Possible Fields of Application	p. 57
Bioreactor Trends and the Increasing Acceptance of Disposables	p. 66
Special Case: Bioreactors for Patient-Specific Therapies Based on Functional Tissue and Stem Cells	p. 69
Bioreactors for Growing 3D Tissues	p. 70
Bioreactors for Large-Scale Expansion and Differentiation of Stem Cells	p. 72
Conclusions	p. 73
Questions and Problems	p. 74
List of Abbreviations and Symbols	p. 74
References	p. 75
Complementary Reading	p. 82
Special Engineering Aspects	p. 83
Cell Damage by Shear and Aeration	p. 83
General Aspects	p. 83
Model Analysis	p. 85
Cell Damage in Bioreactors	p. 92
Oxygen Supply	p. 102
Introduction	p. 102
Limitations for Oxygen Transfer	p. 105
Oxygen Supply Systems (Aeration Systems)	p. 108
Consequences for Reactor Design and Operation	p. 120
Immobilization of Cells	p. 122
Carriers for Cell Immobilization	p. 123
Encapsulation	p. 134
Culture Modes	p. 136
Principles of Culture Modes	p. 136
Examples of Different Culture Modes	p. 141
Process Strategies for Fed-Batch	p. 147
Process Strategies Applied in Industrial Processes	p. 149
Monitoring and Controlling in Animal Cell Culture	p. 152
Temperature	p. 152
pH	p. 153
Oxygen Partial Pressure	p. 154
Carbon Dioxide Partial Pressure	p. 156
Metabolites and Products	p. 156
Cell Density and Viability	p. 159
Agitation	p. 160
Questions and Problems	p. 160
Problem	p. 160
Problem	p. 160
List of Symbols	p. 162
References	p. 164
Complementary Reading	p. 171
Bioreactor Design and Scale-Up	p. 173
Bioreactor Design	p. 173
Bioreactors for Suspended Cells	p. 176
Fixed Bed and Fluidized Bed Bioreactors: Design, Performance and Scale-Up	p. 199
Membrane Bioreactors	p. 217
Disposable Bioreactors	p. 242
Selection of Bioreactor and Operation Mode	p. 245
How to Grow Mammalian Cells from Cryopreserved Vial to Production Bioreactor	p. 246
Questions and Problems	p. 249
List of Symbols	p. 250
References	p. 253
Complementary Reading	p. 259
Special Applications
Insect Cell-Based Recombinant Protein Production	p. 263
Insect Cell Culture	p. 263
Special Aspects: Engineering Baculoviruses as Vectors	p. 264
Bioreactor Concepts	p. 267
Process Design	p. 268
Optimization of Nutrient Supply	p. 268
Optimization of Production Kinetics	p. 268
Applications	p. 270
Current Trends in Insect Cell-Based Protein Production	p. 270
Elimination of Product Protein Proteolysis	p. 273
Limitations	p. 273
References	p. 274
Complementary Reading	p. 276
Bioreactors for Bioartificial Organs	p. 279
Introduction	p. 279
Cells for Bioartificial Organs	p. 280
Expression of the Adult Cell Phenotype	p. 283
Bioreactor Design for Bioartificial Organs	p. 285
Extravascular (EV) Bioreactors	p. 289
Intravascular (IV) Bioreactors	p. 295
Membrane Immunoprotection in Bioartificial Organs	p. 302
Commercial Bioreactors and Applications	p. 304
List of Symbols	p. 310
References	p. 311
Plant Cell-Based Bioprocessing	p. 315
Plant Cell Culture Basics	p. 316
Characteristics of Plant Cells and Culture Conditions	p. 316
Media	p. 317
Plant Cell Culture Types and Their In Vitro Initiation	p. 319
Routine Working Methods in Plant Cell Cultivation	p. 326
Bioreactors for Plant Cell Cultures	p. 330
General Considerations	p. 330
Suitable Bioreactors for Plant Cell Suspension Cultures	p. 332
Suitable Bioreactors for Hairy Roots	p. 335
Approaches to Improving Productivity in Plant Cell-Based Bioprocessing	p. 340
Application Examples and Potential Active Agent Candidates	p. 342
Conclusions	p. 343
Questions and Problems	p. 344
List of Abbreviations and Symbols	p. 345
References	p. 347
Complementary Reading	p. 356
Index	p. 357
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