Stem Cells in Neurotoxicology

1st Edition, Volume 12 - September 25, 2024
Imprint: Academic Press
Editors: Lucio G. Costa, Aaron B. Bowman, Michael Aschner
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 2 5 4 - 4
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 2 5 7 - 5

Stem Cells in Neurotoxicology, Volume Twelve in the Advances in Neurotoxicology series, presents interesting chapters written by an international board of authors. Chapters in this… Read more

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Stem Cells in Neurotoxicology, Volume Twelve in the Advances in Neurotoxicology series, presents interesting chapters written by an international board of authors. Chapters in this new release include Brain organoids as a translational model of human developmental neurotoxicity, Self-organizing human neuronal cultures in the modeling of environmental impacts on learning and intelligence, Utilization of human stem cell/neural progenitor tests to examine neurotoxic impacts on differentiation, Characterization of neuronal and other cellular sub-types in human stem cell cortical neuron differentiations, Utility of human stem cell models to study persistent neurotoxicity, and Utility of human stem cell models to study chronic neurotoxicity.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Chapter One: The long road to the development of stem cells as a model for central nervous system health and disease
Abstract
1 Introduction
2 Stem cells: A historical perspective
3 The road to pluripotency
4 To have some nerve (Cells): Differentiation to neural lineages
5 Concluding remarks
References
Chapter Two: Immortalized neuronal lines versus human induced pluripotent stem cell-derived neurons as in vitro toxicology models
Abstract
1 Characterization and utilization of cell lines
2 Characterization and utilization of hiPSC-derived neurons
3 Incorporating immortalized cell line and hiPSC-derived models in toxicological study design
4 Discussion and future outlook
5 Concluding remarks
Acknowledgment
References
Chapter Three: Brain organoids as a translational model of human developmental neurotoxicity
Abstract
1 Introduction
2 The journey to in vitro DNT testing
3 Current state and advances in brain organoid technology
4 Applications of brain organoids in DNT testing
5 Challenges and limitations
6 The importance of quality assurance for DNT testing with brain organoids
7 Future directions and recommendations
8 Ethical considerations
9 Conclusions
Acknowledgments
References
Chapter Four: Self-organizing human neuronal cultures in the modeling of environmental impacts on learning and intelligence
Abstract
1 Introduction
2 Self-organizing neural cultures
3 Environmental impacts on neurodevelopment
4 Modeling learning and intelligence
5 Organoid intelligence: a new frontier in biocomputing and cognition research
6 Use of human neuronal cultures in environmental research
7 Ethical, legal, and social implications
8 Future directions and innovations
9 Conclusions
Acknowledgments
References
Chapter Five: Utilization of human stem cells to examine neurotoxic impacts on differentiation
Abstract
1 The role of cell differentiation in brain development
2 Embryonic versus induced pluripotent stem cells as in vitro differentiation models
3 Differentiation as an endpoint for neurotoxicity assessment
4 Readouts for neuronal differentiation
5 Considerations for available differentiation routes
6 Current and future applications of stem cell differentiation models
7 Concluding remarks
Acknowledgements
References
Chapter Six: The role of stem cells in the study and treatment of neurodegenerative diseases with environmental etiology
Abstract
1 Introduction
2 Effect of environmental toxins/toxicants on NSCs that may contribute to the etiology of different types of NDDs
3 Stem cell therapy: a promising approach to treat environmental contaminants induced NDDs
4 Conclusion
Acknowledgments
References
Chapter Seven: The use of human iPSC-derived neuronal cultures for the study of persistent neurotoxic effects
Abstract
1 Persistent toxicity
2 Known cases of persistent toxicity throughout toxicological history
3 Persistent effects and the developmental origins of health and disease hypothesis
4 Mechanisms of persistent effects and the potential for hiPSCs
5 Opportunities in experimental designs for the study of persistent effects
6 Concluding remarks
References
Chapter Eight: Simple and reproducible directed differentiation of cortical neural cells from hiPSCs in chemically defined media for toxicological studies
Abstract
1 Introduction
2 Overview of protocol
3 Materials and reagent setup
4 Procedure
5 Conclusions
6 Troubleshooting
References

Lucio G. Costa

Dr. Lucio G. Costa is Professor of Toxicology at the University of Washington in Seattle, and of Pharmacology/Toxicology at the University of Parma Medical School. He received a doctorate in Pharmacology from the University of Milano in 1977, and was a postdoctoral fellow at the University of Texas at Houston. He is a member of several national and international professional organizations, a Fellow of the Academy of Toxicological Sciences, and a European Certified Toxicologist. He received various award for his scientific accomplishments, including the Achievement Award from the Society of Toxicology. He serves in various editorial capacities for several toxicology journals, and is an active manuscript and grant reviewer. Dr. Costa has been the member of dozens of panels and committees at the national and international level dealing with toxicology and risk assessment issues. He has chaired and/or organized symposia at scientific meetings in the United States and internationally. He has been teaching classes in the area of toxicology, neurotoxicology and pharmacology to graduate and medical students for 30 years. He keeps an active research program in the area of neurotoxicology.

Affiliations and expertise

Professor of Toxicology, University of Washington, Seattle, WA, USA

Michael Aschner

Dr. Aschner serves as the Harold and Muriel Block Chair in Molecular Pharmacology at Albert Einstein College of Medicine. He served on numerous toxicology panels (Institute of Medicine, US Environmental Protection Agency, Center for Disease Control), and is a member of the Neurotoxicology and Alcohol study section (NIH). Research in our lab focuses on the following topics: (1) Modulation of C. elegans genes (aat, skn-1, daf-16) that are homologous to mammalian regulators of MeHg uptake and cellular resistance will modify dopaminergic neurodegeneration in response to MeHg exposure. (2) Under conditions of MeHg-induced oxidative stress, Nrf2 (a master regulator of antioxidant responses) coordinates the upregulation of cytoprotective genes that combat MeHg-induced oxidative injury, and that genetic and biochemical changes that negatively impact upon Nrf2 function increase MeHg’s neurotoxicity. (3) PARK2, a strong PD genetic risk factor, alters neuronal vulnerability to modifiers of cellular Mn status, particularly at the level of mitochondrial dysfunction and oxidative stress. Our studies are designed to (1) shed novel mechanistic insight into metal-induced neurodegeneration; (2) identify targets for genetic or pharmacologic modulation of neurodegenerative disorders; (3) increase knowledge of the pathway involved in oxidative stress; (4) develop improved research models for human disease using knowledge of environmental sciences.

Affiliations and expertise

Professor, Department of Molecular Pharmacology, Albert Einstein College of Medicine, NY, USA

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