Replacing Animal Models E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 474

Veröffentlichungsjahr: 2012

Beschreibung

Over the last decade, in vitro models have become more sophisticated and are at a stage where they can provide an effective alternative to in vivo experiments. Replacing Animal Models provides scientists and technicians with a practical, integrated guide to developing culture-based alternatives to in vivo experiments. The book is neither political nor polemical: it is technical, illustrating by example how alternatives can be developed and used and providing useful advice on developing others. After looking at the reasons for and potential benefits of alternatives to animal experiments, the book covers a range of methods and examples emphasising the design considerations that went into each system. The chapters also include 'case studies' that illustrate the ways in which culture models can be used to answer a range of important biological questions of direct relevance to human development, physiology, disease and healing. The thesis of this book is not that all animal experimentation can be replaced, now or in the near future, by equally effective or superior alternatives. Rather, the premise is that there is substantial opportunity, here and now, to do some common types of experiment better in vitro than in vivo, and that doing so will result in both scientific and ethical gains.

Leseprobe

Contents

Cover

Title Page

Copyright

Contributors

Preface

Section 1: Introductory Material

Chapter 1: Potential Advantages of Using Biomimetic Alternatives

Introduction

Scientific reasons to consider alternatives

Non-scientific reasons to consider alternatives

Limits to the use of biomimetic alternatives

Summary

References

Chapter 2: Overview of Biomimetic Alternatives

Introduction

Two-dimensional and suspension cell culture

Three-dimensional (gel-based) cell culture

Organoids

Slice and fragment cultures

Whole-organ culture

Tissue-engineering of organs in culture

Whole-embryo culture

Uses for cultured organoids, tissues and organs

Conclusion

References

Section 2: Culture Methods

Chapter 3: Pancreatic Islets

Introduction

Islets of Langerhans

Uniformity and animal strains

Human material

References

Chapter 4: Endometrial Organoid Culture

Introduction

Design considerations

Methodological considerations

Research applications

Detailed protocols

Acknowledgements

References

Chapter 5: Modelling Lymphatic and Blood Capillary Patterning

Introduction

The different steps of angio- and lymphangiogenesis

Culturing isolated (lymphatic and blood) endothelial cells

Lymphatic and blood endothelial cell discrimination

In vitro dedifferentiation

Suitability of LEC monocultures

The ‘ring assays’

Concluding remarks

Acknowledgements

References

Chapter 6: Precision-cut Lung Slices (PCLS)

Introduction

The history of living slices and the implication for the lung tissue

In vitro models to study lung function

Choosing the appropriate animal species

Airway responses in different species

Response to mediators of the early allergic response (EAR)

Small airways in PCLS

Electric field stimulation in PCLS

Conclusion

References

Chapter 7: Human Colon Tissue in Organ Culture

Introduction

Organ culture maintains histological and biochemical features unique to normal and neoplastic states

The Model

Potential for experimental modulation of the colon organ culture model

Summary

Acknowledgements

References

Chapter 8: Fetal Organ Culture

Introduction

General principles of intact organ culture

Uses for organ cultures

Organ culture of the mouse metanephric kidney

Limitations of organ culture techniques

Conclusion

References

Chapter 9: Design of a Mechanical Loading Device to Culture Intact Bovine Spinal Motion Segments under Multiaxial Motion

Introduction: the clinical problem

Animal models for intervertebral disc degeneration

Development of a next-generation intervertebral disc loading device for application of multiaxial motion

Conclusions

Acknowledgements

References

Chapter 10: Magnetic Assembly of Tissue Surrogates

Introduction

Magnetic cell-manipulation techniques

Devices for magnetic-based cell manipulation

Applications of magnetic assembled tissue surrogates

Advantages and limitations of the magnetic-based tissue-surrogate assembly system

Limitations of magnetic-based tissue assembly

Conclusion and perspectives

References

Chapter 11: Assembly of Renal Tissues by Cellular Self-organization

Introduction

The dissociation–reaggregation technique

Application of the technique to making chimeras

Application to transfection

Production of a more realistic kidney, organized around a single ureteric bud tree

Conclusion

Detailed protocols

Acknowledgements

References

Section 3: Case Studies of Use

Chapter 12: Hierarchical Screening of Pathways: Using Cell and Organ Cultures to Reduce use of Transgenic Mice

Introduction

Background to the project: the need to understand kidney development

Cell line-based strategies for studying mesenchymal- to-epithelial transition and epithelial morphogenesis

Making immortal cell lines for primary screens

Characterizing the cell lines

An example application: the potential importance of src family signalling in collecting duct morphogenesis

Limitations

Dissemination

Acknowledgements

References

Chapter 13: Lung Organoid Culture to Study Responses to Viruses

Introduction

History of the development of lung tissue models

Technical considerations

Experimental results

Perspectives

References

Chapter 14: Organ-cultured Human Skin for the Study of Epithelial Cell Invasion of Stroma

Introduction

Technical and logistical considerations

Use of organ-cultured human skin to study skin physiology and pathophysiology

Epithelial cell invasion of the stroma in organ-cultured skin

EGF-induced invasion in normal skin: relationship to malignant invasion

Summary

References

Chapter 15: Organotypic Mandibular Cultures for the Study of Inflammatory Bone Pathology

Introduction – design considerations and background

Advantages of ex-vivo models – where does this system fit?

A practical culture and imaging system

Applications of the ex-vivo mandible culture system

Detailed instructions

Acknowledgements

References

Chapter 16: Three-Dimensional, High-Density and Tissue Engineered Culture Models of Articular Cartilage

Introduction

Articular cartilage: normal structure and function

Arthritic diseases of articular cartilage: osteoarthritis and rheumatoid arthritis

Animal models of arthritis

The science and art of biomimetic models

Biomimetic culture models of articular cartilage

Cocultures of chondrocytes and synoviocytes

Chondrocyte–macrophage cocultures

Conclusions and future perspectives

Biomimetic alternatives: problems and prospects

The importance of the scientific question and experimental design in choosing the right model system

Justifying the use of animal models for research on arthritis pain

Acknowledgements

References

Chapter 17: Concluding Remarks

References

Appendix 1: Sources of funding for development of culture-based alternatives

Appendix 2: Databases and web-based discussions relevant to development of alternatives

Index

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Contributors

Merja Bläuer Department of Gastroenterology and Alimentary Tract Surgery and Tampere Pancreas Laboratory, Tampere University Hospital, Teiskontie 35, FIN-33521 Tampere, Finland and the Finnish Centre for Alternative Methods (FICAM), Medical School, Building B, FIN-33014 University of Tampere, Finland. [email protected]

J. Leland Booth Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, and §Programs in Immunology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104. [email protected]

Françoise Bruyère Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génopr- otéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, B-4000 Liège, Belgium. [email protected]

Constanze Buhrmann Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilian-University Munich, Pettenkoferstrasse 11, D-80336 Munich, Germany

Hwan-You Chang 101 Kuang Fu Road, Section 2, Department of Medical Science, National Tsing Hua University, Hsin Chu, Taiwan 30013. [email protected]

Michael K Dame Department of Pathology, The University of Michigan, 1301 Catherine Road/Box 5602, Ann Arbor, MI 48109 USA. [email protected]

Jamie A Davies Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XB. [email protected]

Charlotte Erpicum Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, B-4000 Liège, Belgium

Stephen J Ferguson University of Bern, ARTORG Center for Biomedical Engineering Research, Institute for Surgical Technology and Biomechanics, Stauffacherstrasse 78, CH-3014 Bern. [email protected]

Chien-Yu Fu 101 Kuang Fu Road, Section 2, Department of Medical Science, National Tsing Hua University, Hsin Chu, Taiwan 30013. [email protected]

Benjamin Gantenbein-Ritter University of Bern, ARTORG Center for Biomedical Engineering Research, Institute for Surgical Technology and Biomechanics, Stauffacherstrasse 78, CH-3014 Bern [email protected]

Sarah Kelly School of Biosciences, Faculty of Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, United Kingdom. [email protected]

Eli C Lewis Ben-Gurion University of the Negev, Faculty of Health Sciences, Department of Clinical Biochemistry, Soroka University Medical Center, Old Surgery bldg. rm 4-73, P.O.B. 151, Beer-Sheva 84101, ISRAEL [email protected]

Catherine Maillard Bruyère, Françoise: Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, B-4000 Liège, Belgium

Christian Martin Institute of Pharmacology and Toxicology, Univ. Hospital Aachen, Wendlingweg 2, 52074 Aachen. [email protected]

Jordan P Metcalf Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, and Programs in Immunology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104. [email protected]

Ali Mobasheri Musculoskeletal Research Group, Division of Veterinary Medicine, School of Veterinary Medicine and Science, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, United Kingdom. [email protected]

Agnès Noël Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génopr-otéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, B-4000 Liège, Belgium. [email protected]

Mehdi Shakibaei Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilian-University Munich, Pettenkoferstrasse 11, D-80336 Munich, Germany

Alastair J Sloan Tissue Engineering and Reparative Dentistry, School of Dentistry, Cardiff University, Cardiff, UK. [email protected]

Emma L Smith Cardiff Institute of Tissue Engineering and Repair, School of Dentistry, Cardiff University, Cardiff, UK. [email protected]

Guangping Tai Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT. [email protected]

Sarah Y Taylor Tissue Engineering and Reparative Dentistry, School of Dentistry, Cardiff University, Cardiff, UK. *Cardiff Institute of Tissue Engineering and Repair, School of Dentistry, Cardiff University, Cardiff, UK. [email protected]

Stefan Uhlig Institute of Pharmacology and Toxicology, Univ. Hospital Aachen, Wendlingweg 2, 52074 Aachen. [email protected]

Mathieu Unbekandt Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XB. [email protected]

James Varani Department of Pathology, The University of Michigan, 1301 Catherine Road/Box 5602, Ann Arbor, MI 48109 USA. [email protected]

Jochen Walser University of Bern, ARTORG Center for Biomedical Engineering Research, Institute for Surgical Technology and Biomechanics, Stauffacherstrasse 78, CH-3014 Bern [email protected]

Wenxin Wu Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, and §Programs in Immunology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104. [email protected]

Preface

The purpose of this book is to provide a practical guide to replacing in vivo animal experiments with alternative techniques. The authors intend to be neither political nor polemical: there are already quite enough books of that sort on this subject. Rather, the work is meant to be technical, to illustrate by example how alternatives can be developed and used and to provide useful advice on developing others. We have written for an audience of scientists and technicians whose main aim is to do the best science, the best way.

There is, of course, a politically and ethically charged background to all discussions about the use of animals for science, and ethical considerations do provide one powerful driver for changing existing practices. There are also many other reasons: these include doing better science, saving time, saving money, gaining better accessibility to the tissues under study and, in experiments designed to throw light on human biology, avoiding dangerous assumptions about humans and non-human animals having exactly the same physiological responses. Different scientists will be driven to consider alternatives by different sets of reasons in different orders of priority and we do not presume, in this book, to consider any motive more laudable than another. These reasons to explore alternatives to animal experimentation, and their potential benefits, are discussed more fully in Chapter .

There are many different approaches to making useful biomimetic alternatives. These are presented in overview form in Chapter , and examples are then explored in detail in the rest of the book. Discussion of simple cell culture has been avoided, as it is commonplace and well supported by the existing literature. By the same token, completely in silico approaches are not discussed: the focus here is on making artificial ‘tissues’ that mimic the corresponding animal tissue sufficiently well to allow meaningful experiments to be done.

Many methods-centred books consist of little more than collections of recipes for specific techniques. As a reader, I find this format frustrating because I seldom want to repeat exactly what someone else has done, but wish rather to use their methods developed for biological system, X as an inspiration to develop a method suitable for biological system Y. Therefore, while this book does include recipes, the emphasis is on chapter authors discussing the design considerations that went in to their systems, in a way that should assist and inspire others. The chapters also include ‘case studies’ that illustrate the ways in which culture models can be used to answer a range of important biological questions of direct relevance to human development, physiology, disease and healing.

It is important to note that the thesis of this book is not that all animal experimentation can be replaced, now or in the near future, by equally effective or superior alternatives, and the contents of this book cannot justifiably be used to support such an argument. Rather, the thesis is that there is substantial opportunity, here and now, to do some common types of experiment better in vitro than in vivo, and that doing so will result in both scientific and ethical gains.

Jamie DaviesUniversity of Edinburgh

SECTION 1

Introductory Material

CHAPTER 1

Potential Advantages of Using Biomimetic Alternatives

Jamie Davies

Introduction

Animal experimentation has long been one of the cornerstones of biological and biomedical research. In fields from surgery to physiology and from pathology to pharmacology, in vivo models have been dominant for well over a century. It can be argued that many of the successes of modern medicine have been based on animal work. Examples include the use of dogs in the discovery of insulin and its use as a treatment for diabetes mellitus1,2, the use of cats for the invention of the heart–lung machine3, the use of mice in the development of penicillin as a clinical antibiotic4, of rats in the identification of the first drugs effective against psychiatric disorders5 and of mice in the development of clinically-useful antiviral compounds6. In recent decades, the rise of transgenic technology has meant that even fields such as molecular biology, that traditionally used cells rather than animals, now involve a significant number of in vivo studies. Current enthusiasm for transgenic mice has meant that a previously gently declining rate of use of vertebrate animals in science has reversed to become a steady rise (Figure 1.1).

Figure 1.1 UK data for animal use between 1998 and 2009 illustrates trends that are common across the scientific world: use of most species has gently fallen but the use of mice has risen strongly, driven mainly by transgenic models.

With the apparent historical success of in vivo investigations, it may seem surprising that so many scientists are now putting so much effort into developing alternatives. There are, however, good reasons for this development, some based on avoiding or reducing the problems that have always been associated with animal work, and some aiming to maximize the opportunities that new technologies make available. The purpose of this short introductory chapter is to give an overview of some of the reasons to consider developing culture-based alternatives or, where a move to an entirely culture-based programme of work would be inadvisable, to consider ways to combine culture and whole-animal approaches.