Drug Testing in Vitro – Breakthroughs and Trends in Cell Culture Technology

Dr. Uwe Marx After finishing medical training Uwe Marx received his doctorate degree in immunology from the Humboldt University, Berlin. In 1995 Dr. Marx was appointed Head of the Department of Medical Biotechnology at Leipzig University and joined ProBioGen, Berlin, in 2000 as Chief Scientific Officer. With more than 20 years of experience in protein drug development and improvement of cell culture techniques, Uwe Marx has published more than 50 scientific papers and holds numerous patents. Dr. Volker Sandig Volker Sandig studied medicine and received his PhD in molecular biology from the Humboldt University, Berlin. He designed experimental strategies for adenovirus based tumor treatment and directed research projects in cell cycle regulation and artificial promoters at the Max Planck Society and Hepavec, a former Berlin-based biotech company. He then joined Merck Research Laboratories, USA and was appointed Vice President Molecular Biology and Virology at ProBioGen, Berlin, Germany in 2000.

Foreword (Rolf Krebs).Preface.List of Contributors.Part I Emerging In-Vitro Culture Technologies.1 Intelligent Biomatrices and Engineered Tissue Constructs: In-Vitro Models for Drug Discovery and Toxicity Testing (Philip Lazarovici, Mengyan Li, Anat Perets, Mark J. Mondrinos, Shimon Lecht, Christopher D. Koharski, Paul R. Bidez III, Christine M. Finck, and Peter I. Lelkes).1.1 Introduction.1.2 Intelligent Biomaterials and Scaffolds for Tissue Engineering.1.3 Fabrication of Scaffolds for Tissue Engineering.1.4 Progress and Achievements in Liver Tissue Engineering.1.5 Cardiac Tissue Engineering: Cells and Models.1.6 In-Vitro-Engineered Pulmonary Tissue Models: Progress and Challenges.1.7 In-Vitro Models of the Blood-Brain Barrier (BBB).1.7.5 Conclusions for BBB In-Vitro Models.References.2 An Overview on Bioreactor Design, Prototyping and Process Control for Reproducible Three-Dimensional Tissue Culture (Ralf Portner and Christoph Giese).2.1 Introduction.2.2 Important Aspects for Bioreactor Design.2.3 Culture Systems and Bioreactors Used in Tissue Engineering.2.4 The Operation of Bioreactors.2.5 3D Systems Used for Drug Testing.2.6 Modeling of Bioreactor Systems for Tissue Engineering.2.7 The Artifi cial Immune System.2.8 Conclusions.References.3 An Overview on Bioelectronic and Biosensoric Microstructures Supporting High-Content Screening in Cell Cultures (Andrea A. Robitzki and Andree Rothermel).3.1 The Potential of Drug Development and Demand on High-Content Screening Systems.3.2 Microfabrication Techniques to Generate Miniaturized Chip Components.3.3 Microelectrode-Based Techniques for Analyzing Cellular Parameters: Possible Use of Real-Time and HTS of Drugs Without Labeling.3.4 Concluding Remarks: Secondary Screening for Safety and Cost-Effective Drug Testing and Discovery.References.4 Novel In-Vitro Exposure Techniques for Toxicity Testing and Biomonitoring of Airborne Contaminants (Amanda Hayes, Shahnaz Bakand, and Chris Winder).4.1 Introduction.4.2 The Inhalation of Air Contaminants.4.3 Toxicological Assessment.4.4 In-Vitro Toxicological Studies.4.5 Applications of In-Vitro Test Methods.4.6 In-Vitro Toxicity Endpoints.4.7 In-Vitro Toxicity Testing of Air Contaminants.4.8 Conclusions.References.Part II Primary Tissues and Cell Lines in Drug Screening/Testing.5 Drug Screening Using Cell Lines: Cell Supply, High-Throughput and High-Content Assays (Christa Burger, Oliver Poschke, and Mirek R. Jurzak).5.1 Introduction.5.2 Cell Lines for HTS.5.3 Conventional Cellular Screening Assays.5.4 The Defi nition of High-Content Screening.5.5 Outlook.References.6 Cell Lines and Primary Tissues for In-Vitro Evaluation of Vaccine Effi cacy (Anthony Meager).6.1 Introduction.6.2 Measurement of Antigen Expression.6.3 Post-Vaccination Testing.6.4 Future Directions.References.7 Designer Cells Derived from Primary Tissue and Designed Cell Lines as a Sustainable Cell Source for Drug Discovery and Safety Assessment (Volker Sandig and Ingo Jordan).7.1 Introduction.7.2 Suitability and Limitations of Primary Cells as Physiologic Models.7.3 Tumor Cell Lines: Sometimes an Alternative.7.4 Immortalization by Design: Infi nite Proliferation and a Differentiated Phenotype?7.5 Designed Cells in Complex Drug Tests.References.8 How Human Embryonic Stem Cell Research Can Impact In-Vitro Drug Screening Technologies of the Future (Andre Schrattenholz and Martina Klemm).8.1 Introduction.8.2 First Excursion: Protein Surrogate Biomarker Signatures.8.3 Second Excursion: Validation.8.4 Reproductive Toxicology and In-Vitro Tests.8.5 Reproductive Toxicology and hESC.8.6 Effi cacy and Mode of Action Studies: Systems Biology Using Embryonic Stem Cell-Based Screening Systems.8.7 Conclusions and Outlook.References.Part III The Use of Human Tissues in Drug Discovery: Scientifi c, Ethical, Legal, and Regulatory Environments.9 Availability, Standardization and Safety of Human Cells and Tissues for Drug Screening and Testing (Glyn N. Stacey and Thomas Hartung).9.1 Introduction.9.2 Availability of Human Cells and Tissues for In-Vitro Testing.9.3 Standardization of Cells and Tissues for Testing Purposes.9.4 Safety Issues.9.5 The Validation of Cell- and Tissue-Based Assays.9.6 Conclusions and Future Prospects.References.10 Ethical Environment and Scientifi c Rationale Towards In-Vitro Alternatives to Animal Testing: Where Are We Going? (Horst Spielmann).10.1 Introduction.10.2 Legal Framework in Europe for Developing Alternatives to Experimental Animals.10.3 Cell and Tissue Culture Systems used in Pharmacology and Toxicology.10.4 Drug-Metabolizing Systems.10.5 Reductions in Experimental Animal Numbers During the Past Decade in Europe: The Situation in Germany.10.6 Reducing Animal Numbers in Regulatory Testing by International Harmonization of Test Guidelines.10.7 Harmonization of OECD Guidelines for the Testing of Chemicals.10.8 Principles of Scientifi c Validation: The Amden Validation Workshops.10.9 Regulatory Acceptance of the Successfully Validated 3T3 NRU In-Vitro Phototoxicity Test.10.10 Use of QSAR and Physico-Chemical Exclusion Rules to Predict Skin Irritation Potential.10.11 Alternative Methods Used in the Development and Safety Testing of Drugs, Biologicals, and Medical Devices.10.12 The Way Forward.References.Part IV Summary and Visions.11 How Drug Development of the 21st Century Could Benefi t from Human Micro-Organoid In-Vitro Technologies (Uwe Marx).11.1 Introduction.11.2 One Hundred Years of In-Vitro Culture.11.3 A Unique Chance Has Been Created by Nature.11.4 How Do We Explore This Unique Chance?11.5 A Roadmap to Enforce New Platform Technologies.11.6 Outlook.References.Subject Index.