Stems cells in toxicology and medicine / [edited by] Saura C. Sahu.
A comprehensive and authoritative compilation of up-to-date developments in stem cell research and its use in toxicology and medicine -Presented by internationally recognized investigators in this exciting field of scientific research -Provides an insight into the current trends and future direction...
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Language: | English |
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Chichester, UK ; Hoboken, NJ :
John Wiley & Sons,
2017.
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Table of Contents:
- Intro
- Title Page
- Copyright Page
- Contents
- List of Contributors
- Preface
- Acknowledgements
- Part I
- Chapter 1 Introduction
- References
- Chapter 2 Application of Stem Cells and iPS Cells in Toxicology
- 2.1 Introduction
- 2.2 Significance
- 2.3 Stem Cell (SC) Classification
- 2.4 Stem Cells and Pharmacotoxicological Screenings
- 2.5 Industrial Utilization Showcases Stem Cell Technology as a Research Tool
- 2.6 Multipotent Stem Cells (Adult Stem Cells) Characteristics and Current Uses
- 2.7 Mesenchymal Stem Cells (Adult Stem Cells)
- 2.8 Hematopoietic Stem Cells (Adult Stem Cells)
- 2.9 Cardiotoxicity
- 2.10 Hepatotoxicity
- 2.11 Epigenetic Profile
- 2.12 Use of SC and iPSC in Drug Safety
- 2.12.1 Potential Benefits of Stem Cell Use in Other Areas
- 2.12.2 Methodologies
- 2.12.3 Economic Benefits of Stem Cell Use
- 2.13 Conclusions and Future Applications
- Acknowledgments
- References
- Chapter 3 Stem Cells: A Potential Source for High Throughput Screening in Toxicology
- 3.1 Introduction
- 3.2 Stem Cells
- 3.2.1 Embryonic Stem Cells (ESCs)
- 3.2.2 Foetal Stem Cells
- 3.2.3 Adult Stem Cells
- 3.2.4 Adult Stem Cells in Other Tissues
- 3.3 High Throughput Screening (HTS)
- 3.3.1 Current Strategies and Types of High Throughput Screening
- 3.3.2 In Vitro Biochemical Assays
- 3.3.2.1 Fluorescent Based Assays
- 3.3.2.2 Luminescence-Based Assays
- 3.3.2.3 Colorimetric and Chromogenic Assays
- 3.3.2.4 Mass Spectroscopy (MS) Based Detection Assays
- 3.3.2.5 Chromatography-Based Assays
- 3.3.2.6 Immobilization and Label-Free Detection Assays
- 3.3.3 Cell-Based Assays
- 3.3.3.1 Reporter Gene Assays
- 3.3.3.2 Cell-Based Label Free Readouts
- 3.4 Need for a Stem Cell Approach in High Throughput Toxicity Studies
- 3.5 Role of Stem Cells in High Throughput Screening for Toxicity Prediction.
- 3.5.1 Applications of Stem Cells in Cardiotoxicity HTS
- 3.5.2 Applications of Stem Cells in Hepatotoxicity HTS
- 3.5.3 Applications of Stem Cells in Neurotoxicity HTS
- 3.6 Conclusion
- Acknowledgement
- Disclosure Statement
- Author's Contribution
- References
- Chapter 4 Human Pluripotent Stem Cells for Toxicological Screening
- 4.1 Introduction
- 4.2 The Biological Characteristics of hPSCs
- 4.2.1 The Biological Characteristics of hESCs
- 4.2.2 The Biological Characteristics of hiPSCs
- 4.3 Screening of Embryotoxic Effects using hPSCs
- 4.3.1 Screening of Embryotoxic Effects using hESCs
- 4.3.2 Screening of Embryotoxic Effects using hiPSCs
- 4.4 The Potential of hPSC-Derived Neural Lineages in Neurotoxicology
- 4.4.1 The Challenge of hPSC s-Derived Neural Lineages in Neurotoxicology Applications
- 4.4.2 The New Biomarkers in Neurotoxicology using hPSC -Derived Neural Lineages
- 4.4.2.1 Gene Expression Regulation
- 4.4.2.2 Epigenetic Markers
- 4.4.2.3 Mitochondrial Function
- 4.4.3 The New Methods in Neurotoxicology using hPSC -Derived Neural Lineages
- 4.4.3.1 High-Throughput Methods
- 4.4.3.2 Three-Dimensional (3-D) Culture
- 4.5 The Potential of hPSC-Derived Cardiomyocytes in Cardiotoxicity
- 4.5.1 The Challenge of hPSC-Derived Cardiomyocytes in Cardiotoxicology Applications
- 4.5.2 The New Biomarkers in Cardiotoxicology using hPSC-Derived Cardiomyocytes
- 4.5.2.1 Gene Expression
- 4.5.2.2 Multi-Electrode Array
- 4.5.3 High-Throughput Methods
- 4.6 The Potential of hPSC-Derived Hepatocytes in Hepatotoxicity
- 4.6.1 The Challenge of hPSCs-Derived Hepatocytes in Hepatotoxicology Application
- 4.6.2 The New Biomarkers in Hepatotoxicology using hPSC -Derived Hepatocytes
- 4.6.3 The New Methods in Hepatotoxicology using hPSC -Derived Hepatocytes.
- 4.6.3.1 iPSC-HH-Based Micropatterned Co-Cultures (iMPCC s) with Murine Embryonic Fibroblasts
- 4.6.3.2 Suspension Culture of Aggregates of ES Cell-Derived Hepatocytes
- 4.6.3.3 Long-Term Exposure to Toxic Drugs
- 4.7 Future Challenges and Perspectives for Embryotoxicity and Developmental Toxicity Studies using hPSCs
- Acknowledgments
- References
- Chapter 5 Effects of Culture Conditions on Maturation of Stem Cell-Derived Cardiomyocytes
- 5.1 Introduction
- 5.2 Lengthening Culture Time
- 5.3 Substrate Stiffness
- 5.4 Structured Substrates
- 5.5 Conclusions
- Disclaimer
- References
- Chapter 6 Human Stem Cell-Derived Cardiomyocyte In Vitro Models for Cardiotoxicity Screening
- 6.1 Introduction
- 6.1.1 Cardiotoxicity in Preclinical and Clinical Drug Development
- 6.1.2 Functional Cardiotoxicity
- 6.1.3 Structural Cardiotoxicity
- 6.1.4 Requirement for Improved In Vitro Models to Predict Human Cardiotoxicity
- 6.2 Overview of hPSC-Derived Cardiomyocytes
- 6.3 Human PSC-CM Models for Cardiotoxicity Investigations
- 6.3.1 hPSC-CMs for the Assessment of Electrophysiological Cardiotoxicity
- 6.3.1.1 Patch Clamp Assays
- 6.3.1.2 Voltage Sensitive Dyes (VSDs)
- 6.3.1.3 Optogenetics
- 6.3.1.4 Multielectrode Array (MEA) Assays
- 6.3.1.5 Impedance Assays
- 6.3.1.6 Calcium Imaging Assays
- 6.3.2 hPSC-CMs for the Assessment of Contractile Cardiotoxicity
- 6.3.2.1 Muscular Thin Films
- 6.3.2.2 Engineered Heart Tissues (EHTs)
- 6.3.2.3 Impedance Assays
- 6.3.2.4 Calcium Imaging Assays
- 6.3.3 hPSC-CMs for the Assessment of Structural Cardiotoxicity
- 6.3.3.1 Mechanisms of Cardiomyocyte Cell Death as Endpoints in Drug Screening
- 6.3.3.2 High Content Analysis
- 6.3.3.3 Impedance Assays
- 6.3.3.4 SeaHorse Flux Analysers
- 6.3.3.5 Complex and 3D Models
- 6.4 Conclusions and Future Direction
- References.
- Chapter 7 Disease-Specific Stem Cell Models for Toxicological Screenings and Drug Development
- 7.1 Evidence for Stem Cell-Based Drug Development and Toxicological Screenings in Psychiatric Diseases, Cardiovascular Diseases and Diabetes
- 7.1.1 Introduction into Stem-Cell Based Drug Development and Toxicological Screenings
- 7.1.2 Relevance for Psychiatric and Cardiovascular Diseases
- 7.1.3 Advantages of Human Disease-Specific Stem Cell Models
- 7.1.4 Pluripotent Stem Cell Models
- 7.1.5 Reprogramming of Somatic Cells for Disease-Specific Stem Cell Models
- 7.1.6 Transdifferentation of Somatic Cells for Disease-Specific Stem Cell Models
- 7.2 Disease-Specific Stem Cell Models for Drug Development in Psychiatric Disorders
- 7.2.1 Disease-Specific Stem Cell Models Mimicking Neurodegenerative Disorder
- 7.2.2 Disease-Specific Stem Cell Models Mimicking AD
- 7.2.3 Disease-Specific Stem Cell Models Mimicking Neurodevelopmental Disorders
- 7.2.4 Disease-Specific Stem Cell Models Mimicking SCZ
- 7.3 Stem Cell Models for Cardiotoxicity and Cardiovascular Disorders
- 7.3.1 Generating Cardiomyocytes In Vitro
- 7.3.2 Generating Microphysiological Systems to Mimic the Human Heart
- 7.3.3 Disease-Modeling using Microphysiological Cardiac Systems
- 7.4 Stem Cell Models for Toxicological Screenings of EDCs
- 7.4.1 In Vitro Analysis of EDCs in Reproduction and Development
- 7.4.2 In Vitro Analysis and Toxicological Screenings of Drugs
- References
- Chapter 8 Three-Dimensional Culture Systems and Humanized Liver Models Using Hepatic Stem Cells for Enhanced Toxicity Assessment
- 8.1 Introduction
- 8.2 Hepatic Cell Lines and Primary Human Hepatocytes
- 8.3 Embryonic Stem Cells and Induced Pluripotent Stem-Cell Derived Hepatocytes
- 8.4 Ex Vivo: Three-Dimensional and Multiple-Cell Culture System
- 8.5 In Vivo: Humanized Liver Models.
- 8.6 Summary
- Acknowledgments
- References
- Chapter 9 Utilization of In Vitro Neurotoxicity Models in Pre-Clinical Toxicity Assessment
- 9.1 Introduction
- 9.1.1 Limitations of Animal Models and the Utility of In Vitro Assays for Neurotoxicity Testing
- 9.1.2 How Regulatory Requirements Can Shape the Development of In Vitro Screening Tools and Efforts
- 9.1.3 In Vitro Assays as Useful Tools for Assessing Neurotoxicity in a Pharmaceutical Industry Setting
- 9.2 Current Models of Drug-Related Clinical Neuropathies and Effects on Electrophysiological Function
- 9.2.1 Neuropathy Assessment
- 9.2.2 Seizure Potential and Electrophysiological Function Assessments
- 9.2.3 Multi Electrode Arrays to Model Electrophysiological Changes Upon Drug Treatment
- 9.3 Cell Types that Can Potentially Be Used for In Vitro Neurotoxicity Assessment in Drug Development
- 9.3.1 Primary Cells Harvested from Neuronal Tissues
- 9.3.2 Immortalized Cells and Cell Lines
- 9.3.3 Induced Pluripotent Stem (iPS) Derived Cells
- 9.4 Utility of iPSC Derived Neurons in In Vitro Safety Assessment
- 9.4.1 iPSC Derived Neurons in Electrophysiology
- 9.4.2 iPSC Derived Neurons to Study Neurite Dynamics
- 9.5 Summary of Key Points for Consideration in Neurotoxicity Assay Development
- 9.6 Concluding Remarks
- References
- Chapter 10 A Human Stem Cell Model for Creating Placental Syncytiotrophoblast, the Major Cellular Barrier that Limits Fetal Exposure to Xenobiotics
- 10.1 Introduction
- 10.2 General Features of Placental Structure
- 10.3 The Human Placenta
- 10.4 Human Placental Cells in Toxicology Research
- 10.5 Placental Trophoblast Derived from hESC
- 10.6 Isolation of Syncytial Areas from BAP-Treated H1 ESC Colonies
- 10.7 Developmental Regulation of Genes Encoding Proteins Potentially Involved in Metabolism of Xenobiotics.