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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Bibliographic Details
Online Access: Full Text (via EBSCO)
Other Authors: Sahu, Saura C. (Editor)
Format: eBook
Language:English
Published: Chichester, UK ; Hoboken, NJ : John Wiley & Sons, 2017.
Subjects:
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.