Human stem cell toxicology / edited by James L. Sherley.

Format:

Book

Contributor:

Sherkey, James L., editor.

Royal Society of Chemistry (Great Britain), issuing body.

Series:

Issues in toxicology ; 29.

Issues in Toxicology, 1757-7179 ; 29

Language:

English

Subjects (All):

Stem cells.

Physical Description:

1 online resource (316 pages) : illustrations (some color).

Edition:

1st ed.

Place of Publication:

Cambridge, England : Royal Society of Chemistry, 2016.

Summary:

Presents the research, knowledge, and technology for detecting cytotoxic agents and addresses emerging new cell-based approaches for technical innovation. Targets university students, academics and industrialists in toxicology, pharmaceutical sciences, tissue and stem cell biology.

Contents:

Cover

Contents

Chapter 1 Addressing Challenges to Progress in Human Stem Cell Toxicology Concepts and Practice

1.1 Filling in the Stem Cell Gap in Human Toxicology

1.2 Historical Impact of the Hierarchical, Anatomical, Sub-disciplinary Structure of Toxicological Sciences

1.3 Human Stem Cell Toxicology as a Stem Cell Exact Science

1.4 Health and Medical Applications for Human Stem Cell Toxicological Sciences

1.5 Introducing the Future Diverse Impacts of Human Stem Cell Toxicology

Acknowledgments

References

Chapter 2 Alternative Methods in Haematopoietic Stem Cell Toxicology

2.1 Introduction

2.2 Haematopoietic Stem Cell Toxicity or Hematotoxicity

2.2.1 Sources of Haematopoietic Stem Cell Toxicity

2.2.2 Importance of Studying Haematopoietic Stem Cell Toxicity

2.2.3 Haematopoietic Stem Cell Toxicity in Drug Development

2.3 Colonogenic Assays as Predictors of Haematopoietic Stem Cell Toxicity

2.3.1 CFU-GM Colonogenic Assay

2.3.2 CFU-Mk Colonogenic Assay

2.3.3 BFU-E Colonogenic Assay

2.3.4 Lymphoid Lineage Based Colonogenic Assays

2.4 Conclusions

Chapter 3 High-throughput Screening of Toxic Chemicals on Neural Stem Cells

3.1 Neural Stem Cells

3.2 Toxic Chemicals in the Environment

3.3 Mechanisms of Neural Stem Cell Toxicity

3.3.1 Ion Channel Blocking

3.3.2 Drug Metabolism Effects

3.3.3 Oxidative Stress

3.3.4 DNA/RNA Denaturation

3.3.5 Membrane Compromise

3.3.6 Other Mechanisms of Neurotoxicity

3.4 NSC Differentiation

3.5 Conventional In vitro Assays for Toxicity Screening against Neural Stem Cells

3.5.1 Well Plate Assays

3.5.2 Cellular Microarray Assays

3.5.3 Microfluidic Assays

3.5.4 Other Assays

3.6 Challenges of Conventional In vitro Approaches in Neurotoxicity Screening.

3.7 Conclusions and Future Directions

Chapter 4 The Role of Catecholamines in Stem Cell Mobilisation

4.1 Introduction

4.2 Catecholamines

4.3 Catecholamines and Stem Cell Mobilisation

4.3.1 Endothelial Progenitor Cells

4.3.2 Mesenchymal Stem Cells

4.3.3 Catecholamines and Stem Cell Biology

4.4 Consequences of Catecholamine-modulating Agents for Stem Cell Toxicity

4.4.1 Other Considerations

4.5 Concluding Comments

Chapter 5 Toxicological Risk Assessment - Proposed Assay Platform Using Stem and Progenitor Cell Differentiation in Response to Environmental Toxicants

5.1 Introduction

5.1.1 Toxicity

5.1.2 Environmental Toxicology

5.1.3 Predictive Toxicology

5.1.4 Automated High Content Imaging and High Throughput, or High Content, Screening

5.1.5 Risk Assessment

5.1.6 Components of Risk Assessment

5.2 Environmental Toxicological Risk Assessment Employing an Assay Platform That Uses Stem and Progenitor Cell Differentiation

5.2.1 Endothelial Colony Forming Cells (ECFCs)

5.2.2 ECFCs are Sensitive to Low-dose Ionizing Radiation (LDIR)

5.2.3 Individual ECFC Cultures Exhibit Donor-related LDIR Responses

5.2.4 The Profiling of Intracellular Signal Transduction Pathways Provides an Insight into the Mechanism of LDIR Toxicity

5.3 Current State of ECF Platform Development

5.3.1 Impedance-based Analysis of ECFC Viability after Exposure to Environmental Toxicants

5.3.2 ECFCs Exhibit Lot-to-lot Variability in Toxicant Response

5.3.3 Development of a Novel ROS Assay Using ECFCs

5.3.4 Density-dependent ROS Levels in Cultured ECFCs

5.3.5 Signal Transduction Assays in Toxicant-treated ECFCs

5.4 Bioanalytical Method Validation

5.4.1 Development of a Quantitative High Content Imaging (QHCA) Platform Using ECFCs.

5.4.2 Optimize Culture Conditions for High-throughput Screening

5.4.3 Initiate Translation of Assay to 384-Well Plates

5.4.4 Incorporation of Automation to Increase Throughput

5.4.5 Validation of the ECFC QHCA

5.4.6 Determining the Z' factor of the Cell Death Assays Using Positive and Negative Controls

5.4.7 Assessing Sources of Assay Variability Including Manual Pipetting, Plating and Edge Effects

5.4.8 Determining Day-to-day Variability of EC50 for Each Assay

5.4.9 Determining Significant Biological Replicate Power

5.4.10 Perform the High-throughput Assay Using Compounds from the ToxCastTM Phase I Library

5.4.11 Incorporation of the Toxicant-induced ECFC Differentiation Assays into the QHCA Screen

5.4.12 Establish a Repository of ECFCs from Various Donors

5.5 Final Thoughts

Chapter 6 Current Developments in the Use of Human Stem Cell Derived Cardiomyocytes to Examine Drug-induced Cardiotoxicity

6.1 Introduction

6.2 Constraints Due to Species Differences

6.3 Stem Cells and iPSC-CMs

6.4 Limitations with Stem Cells

6.5 Stem Cells in Cardiovascular Safety Pharmacology

6.6 Disease Models Based on iPSC-CMs

6.7 Generation of iPSC-CMs - Considerations on Differentiation, Maturity, Heterogeneity and Purification Protocols

6.7.1 Differentiation

6.7.2 Maturity

6.7.3 Heterogeneity

6.7.4 Purification

6.8 Use of iPSC-CMs in Phenotypic Assays

6.9 Assay Technologies Incorporating iPSC-CMs and hESC-CMs

6.9.1 Manual Patch Clamp

6.9.2 Automated Patch Clamp

6.9.3 MEA (Microelectrode Array)

6.10 CiPA: Comprehensive In vitro Proarrhythmia Assay

6.11 Conclusion

Chapter 7 Pesticides and Hematopoietic Stem Cells

7.1 Pesticide Toxicity-induced Disorders of Hematopoietic System

7.1.1 Hematopoietic System and Hematotoxic Pesticides.

7.1.2 Pesticide-induced Aplastic Anemia: A Rare but Severe Hematopathology due to Stem Cell Failure

7.1.3 Assessment of Hematotoxicity

7.2 Pesticide Toxicity on Hematopoietic Stem Cells and their Microenvironment

7.2.1 Oxidative Stress Induction

7.2.2 Apoptosis Induction

7.2.3 Alteration of Developmental Signaling Pathways

7.3 Experimental Medicine Against Pesticide Toxicity-induced Hematopoietic Failure

7.4 Future Direction

Chapter 8 Epigenetic Impact of Stem Cell Toxicants

8.1 Introduction

8.2 Epigenetic Regulation of Stem Cells

8.3 Stem Cell Toxicants as Modulators of Epigenetic Programming

8.3.1 Heavy Metals

8.3.2 Pharmaceuticals

8.4 Conclusion

Chapter 9 Metakaryotic Cancer Stem Cells are Constitutively Resistant to X-Rays and Chemotherapeutic Agents, but Sensitive to Many Common Drugs

9.1 Introduction

9.1.1 Introduction to Metakaryotic Biology

9.2 Materials and Methods

9.2.1 Methods for Studies of Metakaryotic Cancer Stem Cells In vivo and In vitro

9.3 Results

9.3.1 Observations in Tumors after Radiation Therapy and Chemotherapy

9.3.2 Observations in Cell Cultures

9.4 Discussion

9.4.1 Stem Cells in Human Tumors and Tumor-derived Cell Lines are Amitotic, Metakaryotic Cells

9.4.2 Assays that Recognize and Measure the Toxicity of Radiation and Chemicals to Metakaryotic Stem Cells

9.4.3 Growth and Development of Turnover Units in HT-29 Cultures

9.4.4 Metakaryotic Stem Cells are Resistant to Doses of X-Rays and Drug Classes Commonly in Use for Cancer Chemotherapy

9.4.5 Metakaryotic Stem Cells are Sensitive to Many Drugs in Common Use: Verapamil, Metformin, NSAIDS and Antibiotics

9.4.6 Hypotheses about Metakaryocidal Mechanisms, e.g. Inhibition of Mitochondrial Function.

9.4.7 Other Potential Targets for Metakaryocides: Genome Replication and Segregation

9.4.8 Translation into Clinical Practice

9.4.9 Potential Use of Metakaryocides in Prevention of Cancers and Other Clonal Diseases

9.4.10 Other Considerations

Chapter 10 Distributed Stem Cell Kinetotoxicity: A New Concept to Account for the Human Carcinogenicity of Non-genotoxic Environmental Toxicants

10.1 Introduction

10.2 Results and Discussion

10.2.1 Development of a High-throughput Cell Kinetics Assay for Kinetotoxicity

10.2.2 Use of High-throughput Screening to Detect Benzene and Hydroquinone as Kinetotoxic Agents

10.2.3 Confirmation Studies for Benzene and Hydroquinone Kinetotoxicity

10.2.4 Validation of Benzene and Hydroquinone Kinetotoxicity with DSCs

10.2.5 Use of Microarray Analyses to Discover a Potential Molecular Biomarker for Kinetotoxicity

10.3 Conclusions and Closing Thoughts

10.3.1 Kinetotoxicity, An Extended Concept in Human Stem Cell Toxicology for Carcinogens

10.3.2 Development of a High-throughput Screen for Kinetotoxic Agents

10.3.3 Mechanisms of Kinetotoxicity by Benzene and Hydroquinone

10.3.4 The DSC Specification Problem in Human Stem Cell Toxicology

10.3.5 Looking Forward

10.4 Materials and Methods

10.4.1 Cells

10.4.2 Chemicals

10.4.3 Development of the High-throughput Microplate Assay for Kinetotoxicity

10.4.4 Assays for Self-renewal Kinetics Pattern Determination

10.4.5 Microarray Analyses

Chapter 11 Cancer Stem Cells as Therapeutic Targets

11.1 Introduction

11.2 CSC Markers and Therapeutic Targets

11.3 Signal Transduction in CSCs and Targeted Agents

11.4 Asymmetric Cell Divisions: The Dilemma of Studies on CSCs

11.5 Asymmetric Cell Divisions: Visualization of CSCs and Toxicology.

11.6 Asymmetric Cell Divisions.

Notes:

Includes bibliographical references at the end of each chapters and index.

Description based on print version record.

Description based on publisher supplied metadata and other sources.

OCLC:

958424387