Marx. Sandig. 2006. Drug Testing In Vitro: Breakthroughs and Trends in Cell Culture Technology

=> Wiley

Here, expert scientists from industry and academia share their knowledge on the assembly of functional human tissues in vitro and how to design drug screenings predictive of human exposure. In so doing, they combine the latest technological developments with strategic outlooks, such as novel cell and tissue systems for drug screening and testing, as well as emerging in vitro culture technologies. Equally importantly, the book does not shy away from regulatory acceptance and ethical issues.

Table of contents

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 Pörtner 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 Artificial 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 Andrée 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 Pöschke, 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 (André 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.