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.
Contributors, vii
Preface, xi
Section 1 Introductory Material
1 Potential Advantages of Using Biomimetic Alternatives, 3
2 Overview of Biomimetic Alternatives, 13
Section 2 Culture Methods
3 Pancreatic Islets, 23
4 Endometrial Organoid Culture, 35
5 Modelling Lymphatic and Blood Capillary Patterning, 45
6 Precision-cut Lung Slices (PCLS), 57
7 Human Colon Tissue in Organ Culture, 69
8 Fetal Organ Culture, 81
9 Design of a Mechanical Loading Device to Culture Intact Bovine Spinal Motion Segments under Multiaxial Motion, 89
10 Magnetic Assembly of Tissue Surrogates, 107
11 Assembly of Renal Tissues by Cellular Self-organization, 115
Section 3 Case Studies of Use
12 Hierarchical Screening of Pathways: Using Cell and Organ Cultures to Reduce use of Transgenic Mice, 125
13 Lung Organoid Culture to Study Responses to Viruses, 137
14 Organ-cultured Human Skin for the Study of Epithelial Cell Invasion of Stroma, 151
15 Organotypic Mandibular Cultures for the Study of Inflammatory Bone Pathology, 159
16 Three-dimensional, High-density and Tissue Engineered Culture Models of Articular Cartilage, 167
17 Concluding Remarks, 193
Appendix 1 Sources of funding for development of culture-based alternatives, 195
Appendix 2 Databases and web-based discussions relevant to development of alternatives, 197
Index, 199