Cell and Tissue Reaction Engineering / Edition 1

Cell and Tissue Reaction Engineering / Edition 1

by Martin Fussenegger, Regine Eibl, Dieter Eibl, Ralf Portner, Gerardo Catapano
     
 

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ISBN-10: 3540681752

ISBN-13: 9783540681755

Pub. Date: 11/17/2008

Publisher: Springer Berlin Heidelberg

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

Overview

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.

Product Details

ISBN-13:
9783540681755
Publisher:
Springer Berlin Heidelberg
Publication date:
11/17/2008
Series:
Principles and Practice Series
Edition description:
2009
Pages:
363
Product dimensions:
6.30(w) x 9.40(h) x 0.70(d)

Table of Contents

Part I Mammalian Cells

1 Mammalian Cell Culture Technology: An Emerging Field D. Eibl R. Eibl R. Portner 3

1.1 Definition and History 3

1.2 Fields of Application and Products from Mammalian Cells 6

1.3 Future Prospects 8

1.4 Exercises 9

References 9

Complementary Reading 11

2 Characteristics of Mammalian Cells and Requirements for Cultivation R. Portner 13

2.1 Differences Between Mammalian Cells, Plant Cells and Microbes: Consequences of These Differences 13

2.2 Types of Mammalian Cells 14

2.2.1 From Primary Cells to Permanent (Established) Cell Lines 15

2.2.2 Hybridom Cells for Production of Monoclonal Antibodies 17

2.2.3 Culture Collections and Cell Banking 20

2.3 Culture Media 21

2.4 Characteristics of Cell Growth and Metabolism 24

2.4.1 Short Introduction to Cell Metabolism 24

2.4.2 Glucose, Glutamine and Amino Acids as Carbon and Energy Source 26

2.4.3 The Effects of Lactate and Ammonia 29

2.4.4 Oxygen Uptake and Carbon Dioxide Production 31

2.5 Kinetic Modelling of Cell Growth and Metabolism 32

2.5.1 Introduction to Kinetic Modelling for Mammalian Cells 32

2.5.2 Set-Up of an Unstructured Model 33

2.5.3 Structured Models 44

2.5.4 Conclusions for Set-Up of a Kinetic Model 45

2.6 Questions and Problems 46

List of Symbols 47

References 47

Complementary Reading 53

3 Bioreactors for Mammalian Cells: General Overview D. Eibl R. Eibl 55

3.1 Technical Terminology: Bioreactor/Fermentor, Bioreactor Facility 56

3.2 Suitable Bioreactor Types for Mammalian Cell Cultures 57

3.2.1 Categorization, Functional Principle, Possible Fields of Application 57

3.2.2 Bioreactor Trends and the Increasing Acceptance ofDisposables 66

3.3 Special Case: Bioreactors for Patient-Specific Therapies Based on Functional Tissue and Stem Cells 69

3.3.1 Bioreactors for Growing 3D Tissues 70

3.3.2 Bioreactors for Large-Scale Expansion and Differentiation of Stem Cells 72

3.4 Conclusions 73

3.5 Questions and Problems 74

List of Abbreviations and Symbols 74

References 75

Complementary Reading 82

4 Special Engineering Aspects P. Czermak R. Portner A. Brix 83

4.1 Cell Damage by Shear and Aeration 83

4.1.1 General Aspects 83

4.1.2 Model Analysis 85

4.1.3 Cell Damage in Bioreactors 92

4.2 Oxygen Supply 102

4.2.1 Introduction 102

4.2.2 Limitations for Oxygen Transfer 105

4.2.3 Oxygen Supply Systems (Aeration Systems) 108

4.2.4 Consequences for Reactor Design and Operation 120

4.3 Immobilization of Cells 122

4.3.1 Carriers for Cell Immobilization 123

4.3.2 Encapsulation 134

4.4 Culture Modes 136

4.4.1 Principles of Culture Modes 136

4.4.2 Examples of Different Culture Modes 141

4.4.3 Process Strategies for Fed-Batch 147

4.4.4 Process Strategies Applied in Industrial Processes 149

4.5 Monitoring and Controlling in Animal Cell Culture 152

4.5.1 Temperature 152

4.5.2 pH 153

4.5.3 Oxygen Partial Pressure 154

4.5.4 Carbon Dioxide Partial Pressure 156

4.5.5 Metabolites and Products 156

4.5.6 Cell Density and Viability 159

4.5.7 Agitation 160

4.6 Questions and Problems 160

4.6.1 Problem 160

4.6.2 Problem 160

List of Symbols 162

References 164

Complementary Reading 171

5 Bioreactor Design and Scale-Up G. Catapano P. Czermak R. Eibl D. Eibl R. Portner 173

5.1 Bioreactor Design 173

5.1.1 Bioreactors for Suspended Cells 176

5.1.2 Fixed Bed and Fluidized Bed Bioreactors: Design, Performance and Scale-Up 199

5.1.3 Membrane Bioreactors 217

5.1.4 Disposable Bioreactors 242

5.2 Selection of Bioreactor and Operation Mode 245

5.3 How to Grow Mammalian Cells from Cryopreserved Vial to Production Bioreactor 246

5.4 Questions and Problems 249

List of Symbols 250

References 253

Complementary Reading 259

Part II Special Applications

6 Insect Cell-Based Recombinant Protein Production W. Weber M. Fussenegger 263

6.1 Insect Cell Culture 263

6.2 Special Aspects: Engineering Baculoviruses as Vectors 264

6.3 Bioreactor Concepts 267

6.4 Process Design 268

6.4.1 Optimization of Nutrient Supply 268

6.4.2 Optimization of Production Kinetics 268

6.5 Applications 270

6.6 Current Trends in Insect Cell-Based Protein Production 270

6.6.1 Elimination of Product Protein Proteolysis 273

6.7 Limitations 273

References 274

Complementary Reading 276

7 Bioreactors for Bioartificial Organs G. Catapano 279

7.1 Introduction 279

7.2 Cells for Bioartificial Organs 280

7.2.1 Expression of the Adult Cell Phenotype 283

7.3 Bioreactor Design for Bioartificial Organs 285

7.3.1 Extravascular (EV) Bioreactors 289

7.3.2 Intravascular (IV) Bioreactors 295

7.3.3 Membrane Immunoprotection in Bioartificial Organs 302

7.4 Commercial Bioreactors and Applications 304

List of Symbols 310

References 311

8 Plant Cell-Based Bioprocessing R. Eibl D. Eibl 315

8.1 Plant Cell Culture Basics 316

8.1.1 Characteristics of Plant Cells and Culture Conditions 316

8.1.2 Media 317

8.1.3 Plant Cell Culture Types and Their In Vitro Initiation 319

8.1.4 Routine Working Methods in Plant Cell Cultivation 326

8.2 Bioreactors for Plant Cell Cultures 330

8.2.1 General Considerations 330

8.2.2 Suitable Bioreactors for Plant Cell Suspension Cultures 332

8.2.3 Suitable Bioreactors for Hairy Roots 335

8.3 Approaches to Improving Productivity in Plant Cell-Based Bioprocessing 340

8.4 Application Examples and Potential Active Agent Candidates 342

8.5 Conclusions 343

8.6 Questions and Problems 344

List of Abbreviations and Symbols 345

References 347

Complementary Reading 356

Index 357

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