Phenotyping of Human iPSC-derived Neurons: Patient-Driven Research examines the steps in a preclinical pipeline that utilizes iPSC-derived neuronal technology to better understand neurological disorders and identify novel therapeutics, also providing considerations and best practices. By presenting example projects that identify phenotypes and mechanisms relevant to autism spectrum disorder and epilepsy, this book allows readers to understand what considerations are important to assess at the start of project design. Sections address reproducibility issues and advances in technology at each stage of the pipeline and provide suggestions for improvement. From patient sample collection and proper controls to neuronal differentiation, phenotyping, screening, and considerations for moving to the clinic, these detailed descriptions of each stage of the pipeline will help everyone, regardless of stage in the pipeline.
In recent years, drug discovery in the neurosciences has struggled to identify novel therapeutics for patients with varying indications, including epilepsy, chronic pain, and psychosis. Current treatment options for such patients are decades old and offer little relief with many side effects. One explanation for this lull in novel therapeutics is a lack of novel target identification for neurological disorders (and target identification requires exemplar preclinical data). To improve on the preclinical work that often relies on rodent modeling, the field has begun utilizing patient-derived induced pluripotent stem cells (iPSCs) to differentiate neurons in vitro for preclinical characterization of neurological disease and target identification.
1. Phenotyping of Human iPSC-derived Neurons - p. Page i 2. Cover - p. Page i 3. Front Matter - p. Page ii 4. Table of Contents - p. Page iii 5. Copyright - p. Page iv 6. Dedication - p. Page v 7. Contributors - p. Page v 8. List of Illustrations - p. Page viii 9. List of Tables - p. Page ix 10. Chapter 1 : iPSC culture: best practices from sample procurement to reprogramming and differentiation - p. Page ix 11. Chapter 2 : Phenotypic assay development with iPSC-derived neurons: technical considerations from plating to analysis - p. Page 20 12. Chapter 3 : Derivation of cortical interneurons from human pluripotent stem cells to model neurodevelopmental disorders - p. Page 39 13. Chapter 4 : Development of transcription factor-based strategies for neuronal differentiation from pluripotent stem cells - p. Page 69 14. Chapter 5 : Differentiation of Purkinje cells from pluripotent stem cells for disease phenotyping in vitro - p. Page 91 15. Chapter 6 : Brain organoids: models of cell type diversity, connectivity, and disease phenotypes - p. Page 115 16. Chapter 7 : Human models as new tools for drug development and precision medicine - p. Page 145 17. Chapter 8 : Use of cerebral organoids to model environmental and gene x environment interactions in the developing fetus and neurodegenerative disorders - p. Page 165 18. Chapter 9 : iPSC-derived models of autism: Tools for patient phenotyping and assay-based drug discovery - p. Page 190 19. Chapter 10 : Probing the electrophysiological properties of patient-derived neurons across neurodevelopmental disorders - p. Page 221 20. Chapter 11 : Advantages and limitations of hiPSC-derived neurons for the study of neurodegeneration - p. Page 238 21. Chapter 12 : Developing clinically translatable screens using iPSC-derived neural cells - p. Page 258 22. Chapter 13 : Gene editing hPSCs for modeling neurological disorders - p. Page 282 23. Chapter 14 : Cell therapy and biomanufacturing using hiPSC-derived neurons - p. Page 305 24. Chapter 15 : Ethical considerations for the use of stem cell-derived therapies - p. Page 334 25. Index - p. Page 347
Phenotyping of Human iPSC-derived Neurons: Patient-Driven Research examines the steps in a preclinical pipeline that utilizes iPSC-derived neuronal technology to better understand neurological disorders and identify novel therapeutics, also providing considerations and best practices. By presenting example projects that identify phenotypes and mechanisms relevant to autism spectrum disorder and epilepsy, this book allows readers to understand what considerations are important to assess at the start of project design. Sections address reproducibility issues and advances in technology at each stage of the pipeline and provide suggestions for improvement. From patient sample collection and proper controls to neuronal differentiation, phenotyping, screening, and considerations for moving to the clinic, these detailed descriptions of each stage of the pipeline will help everyone, regardless of stage in the pipeline.
In recent years, drug discovery in the neurosciences has struggled to identify novel therapeutics for patients with varying indications, including epilepsy, chronic pain, and psychosis. Current treatment options for such patients are decades old and offer little relief with many side effects. One explanation for this lull in novel therapeutics is a lack of novel target identification for neurological disorders (and target identification requires exemplar preclinical data). To improve on the preclinical work that often relies on rodent modeling, the field has begun utilizing patient-derived induced pluripotent stem cells (iPSCs) to differentiate neurons in vitro for preclinical characterization of neurological disease and target identification.
1. Phenotyping of Human iPSC-derived Neurons - p. Page i 2. Cover - p. Page i 3. Front Matter - p. Page ii 4. Table of Contents - p. Page iii 5. Copyright - p. Page iv 6. Dedication - p. Page v 7. Contributors - p. Page v 8. List of Illustrations - p. Page viii 9. List of Tables - p. Page ix 10. Chapter 1 : iPSC culture: best practices from sample procurement to reprogramming and differentiation - p. Page ix 11. Chapter 2 : Phenotypic assay development with iPSC-derived neurons: technical considerations from plating to analysis - p. Page 20 12. Chapter 3 : Derivation of cortical interneurons from human pluripotent stem cells to model neurodevelopmental disorders - p. Page 39 13. Chapter 4 : Development of transcription factor-based strategies for neuronal differentiation from pluripotent stem cells - p. Page 69 14. Chapter 5 : Differentiation of Purkinje cells from pluripotent stem cells for disease phenotyping in vitro - p. Page 91 15. Chapter 6 : Brain organoids: models of cell type diversity, connectivity, and disease phenotypes - p. Page 115 16. Chapter 7 : Human models as new tools for drug development and precision medicine - p. Page 145 17. Chapter 8 : Use of cerebral organoids to model environmental and gene x environment interactions in the developing fetus and neurodegenerative disorders - p. Page 165 18. Chapter 9 : iPSC-derived models of autism: Tools for patient phenotyping and assay-based drug discovery - p. Page 190 19. Chapter 10 : Probing the electrophysiological properties of patient-derived neurons across neurodevelopmental disorders - p. Page 221 20. Chapter 11 : Advantages and limitations of hiPSC-derived neurons for the study of neurodegeneration - p. Page 238 21. Chapter 12 : Developing clinically translatable screens using iPSC-derived neural cells - p. Page 258 22. Chapter 13 : Gene editing hPSCs for modeling neurological disorders - p. Page 282 23. Chapter 14 : Cell therapy and biomanufacturing using hiPSC-derived neurons - p. Page 305 24. Chapter 15 : Ethical considerations for the use of stem cell-derived therapies - p. Page 334 25. Index - p. Page 347
