Three Dimensional Human Organotypic Models for Biomedical Research (Current Topics in Microbiology and Immunology, 430)

This edited volume discusses the application of very diverse human organotypic models in major areas of biomedical research. The authors lay a main focus on infectious diseases, cancer, allergies, as well as drug/vaccine discovery and toxicology studies. Representing a valid alternative to laboratory animals, these models are relevant for most areas of translational research. As the contemporary research shows, many human tissues can today be cultivated in vitro and used for several research objectives. This book provides an unprecedented overview of recent developments in an exciting field of research methodology. It is a reference guide for scientists in both academia and industry. Readers can update their knowledge and get hands-on recommendations on how to set up an organotypic model in their lab. Chapters 'Progress on Reconstructed Human Skin Models for Allergy Research and Identifying Contact Sensitizers' and 'Human Organotypic Models for Anti-infective Research' of this book are available open access under a CC BY 4.0 license at link.springer.com. Preface Contents Three Dimensional Human Organotypic Models for Studying Infectious Diseases 219 Human Three-Dimensional Models for Studying Skin Pathogens Abstract 1 Introduction 2 Skin Microbiota: Between Colonization and Infection 3 Skin Colonization and Infection Studies in Human Skin Models 4 Immune Response to Skin Infections 5 Bloodstream-Derived Elements 6 Conclusions and Future Perspectives Competing Interests Bibliography 91 Human Organotypic Respiratory Models Abstract 1 Introduction 2 Organotypic Respiratory Models 2.1 Unicellular 3D Models 2.1.1 Epithelial Models 2.1.2 Fibroblast Models 2.2 Models Built Layer by Layer 2.3 Immunocompetent 3D Models 2.4 Lung-on-a-Chip 2.5 Spheroids and Organoids 2.5.1 Spheroids 2.5.2 Organoids from Progenitor Cells 2.5.3 Organoids from Stem Cells 2.6 Tissue Explants 2.7 Considerations for In Vitro/Ex Vivo Modeling 3 Conclusions and Future Perspectives Acknowledgements References 223 Human Gastrointestinal Organoid Models for Studying Microbial Disease and Cancer Abstract 1 Introduction 2 Organoids for the Study of Host–Pathogen Interactions 2.1 Rotavirus, Norovirus, and Zika Virus 2.2 Helicobacter Pylori 3 Organoid–Immune Cell Co-cultures 3.1 Organoid/Macrophage Co-cultures 3.2 Organoid Co-culture with Antigen-Presenting Dendritic Cells (DCs) 3.3 Organoids Co-cultured with Lymphocytes 4 The Microbiome and Cancer Development 4.1 Microbial Contribution to Disease Development 4.2 Using Organoids to Gain Insight into the Development of Cancer Therapeutics 5 Conclusions Acknowledgements References 130 Human Organotypic Models for Anti-infective Research Abstract 1 Introduction 2 Part 1—State of the Art of Organotypic Models for Anti-infective Research 2.1 Cervical Models 2.2 Intestinal Models 2.3 Respiratory Models 2.4 Brain Models 3 Part 2—in-Depth Overview of Skin Models for Anti-infective Research 3.1 Skin Equivalent Versus Skin Explants 3.2 Use of Human Skin Models in Anti-infective Research 3.3 Conclusion 3.4 Protocol: Culture of Human Skin Equivalents and Skin Explants for Use in Anti-infective Research 3.4.1 Procedure for the Preparation of Human Skin Equivalents 3.4.2 Procedure for the Preparation of Human Skin Explants (Olaniyi et al. 2018) Acknowledgements References Three Dimensional Human Organotypic Models for Studying Non-infectious Diseases 88 Progress on Reconstructed Human Skin Models for Allergy Research and Identifying Contact Sensitizers Abstract 1 Introduction 2 Ex Vivo Skin 3 Reconstructed Human Epidermis (RhE) 4 Bilayered Reconstructed Human Skin (RhS) 5 Immune Competent Skin Models 6 Skin-on-a-Chip 7 Conclusions and Future Perspectives Acknowledgements References 157 Cancer Explant Models Abstract 1 Introduction 2 Framing the Research Question 3 Cancer Hallmarks 3.1 Cancer Stem Cells 3.2 Angiogenesis 3.3 Proliferation and Avoidance of Apoptosis 3.4 Migration/Invasion 3.5 Metastasis 3.6 Metabolism 3.7 Therapy Resistance and Recurrence 3.8 Hypoxia 3.9 Basic Science, Translational, and Clinical Research 4 Tumor Material Sources 4.1 Solid Tumors Versus Liquid Tumors 4.2 Renewable or Consumable 4.3 Patient Primary Materials 4.4 Syngeneic and Allogeneic Murine Tumors 4.5 Carcinogen or Virally-Induced 4.6 Genetically Engineered Mouse Models/Transgenics 4.7 Cancer Cell Lines 5 Cancer Explant Models 5.1 Organotypic Slice 5.2 Xenografts 5.3 Chick Chorioallantoic Membrane 5.4 Liquid-Based 3D Models 5.5 Scaffold-Based 3D Models 5.6 “Tumor-on-a-Chip” 5.7 Transwell and Migration Assays 5.8 Monolayer Culture 6 Discussion 7 Conclusions Acknowledgements References 79 Organotypic Models of Lung Cancer Abstract 1 Introduction 2 Organotypic Models of Lung Cancer 2.1 Ex Vivo Tissue Culture Models 2.1.1 Precision-Cut Lung Slices (PCLSs) 2.1.2 Lung Whole Tissue Explants (WTE) 2.1.3 Summary 2.2 Lung Tumor Xenografts 2.3 Spheroids 2.4 Organoids 2.5 Air–Liquid Interface 2.6 Bioengineering Approaches 2.6.1 Lung-on-a-Chip 2.6.2 Lung 3D Printing 3 Conclusions Acknowledgements References 155 Pancreatic Cancer Organotypic Models Abstract 1 Introduction 1.1 Pancreatic Cancer 1.2 The Importance of 3D Models 2 Pancreatic Organoids 2.1 Overview 2.2 Epithelial Organoids 2.3 Co-culture 3 Pancreatic Organotypics 3.1 Overview 3.2 PDAC Development Models 3.3 PDAC Invasion Models 3.4 PDAC Organotypic Analysis 3.5 Mini-organotypics 4 Other Models 4.1 Spheroids 4.2 Extracellular Matrix Models 4.3 Microfluidics 4.4 Tumour Slice Models 4.5 Mini-pancreas 5 Conclusion References 86 Breast Organotypic Cancer Models Abstract 1 Introduction 1.1 Anatomy of the Human Mammary Gland (HMG) and Development of Breast Cancer 1.2 2D Models in Breast Cancer Research 1.3 In Vivo Models in Breast Cancer Research 2 Organotypic Models for Breast Cancer Research 2.1 Mammospheres: Multicellular 3D Spheroids of Mammary Tumors 2.2 Applications of Mammospheres 2.3 Patient-Derived Tumor Organoids (PDTOs) 2.4 Applications of PDTOs 2.5 Bioreactors 3D and Applications in Breast Cancer Research 2.6 Organotypic Culture of Human Breast Cancer Tissue Slices 2.7 Applications of Organotypic Cultures of Breast Cancer Slices 3 Conclusions References 159 Preclinical Organotypic Models for the Assessment of Novel Cancer Therapeutics and Treatment Abstract 1 Introduction 2 3D in Vivo Models 3 3D In Vitro Models 4 Conclusions Acknowledgements References 142 Overview and Comparison of Intestinal Organotypic Models, Intestinal Cells, and Intestinal Explants Used for Toxicity Studies Abstract 1 Introduction 2 Cell Models 2.1 Primary Cell Cultures 2.2 Cells Derived from Healthy Intestine 2.3 Tumor Cell Models 3 Explant Models 4 Organoids Models 5 Conclusion Acknowledgements References 174 Correction to: Human Organotypic Models for Anti-infective Research Correction to: Chapter “Human Organotypic Models for Anti-infective Research” A. Hendriks et al., in: Current Topics in Microbiology and Immunology, https://doi.org/10.1007/82_2018_130DOI "This edited volume discusses the application of very diverse human organotypic models in major areas of biomedical research. The authors lay a main focus on infectious diseases, cancer, allergies, as well as drug/vaccine discovery and toxicology studies. Representing a valid alternative to laboratory animals, these models are relevant for most areas of translational research. As the contemporary research shows, many human tissues can today be cultivated in vitro and used for several research objectives. This book provides an unprecedented overview of recent developments in an exciting field of research methodology. It is a reference guide for scientists in both academia and industry. Readers can update their knowledge and get hands-on recommendations on how to set up an organotypic model in their lab."--Back cover