Stems cells in toxicology and medicine / editor, Saura C. Sahu.

Format:

Book

Contributor:

Sahu, Saura C., editor.

Language:

English

Subjects (All):

Stem cells--Research.

Stem cells.

Toxicology--Research.

Toxicology.

Physical Description:

1 online resource (591 p.)

Edition:

1st ed.

Place of Publication:

Chichester, West Sussex, England : Wiley, 2017.

Summary:

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 directions of research in this rapidly developing new field * A valuable and excellent source of authoritative and up-to-date information for researchers, toxicologists, drug industry, risk assessors and regulators in academia, industry and government

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

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

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

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

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

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

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

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.

10.7.1 Cytochrome P450 Family Members.

Notes:

Includes bibliographical references and index.

Includes indexes.

Description based on print version record.

ISBN:

9781119135432

1119135435

9781119135425

1119135427

9781119135449

1119135443

OCLC:

957339746