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Chapter 1. Introduction (Part I)
Chapter 2. Transplantation in the future
2. Future directions
Chapter 3. Ethical challenges for using human cells in clinical cell therapy
2. Challenges, ethical, and others
3. Scientific challenges and ethics
4. Societal concerns: legal and economic issues
5. Meeting ethical challenges and three theses
6. Stages and stage-related challenges
7. Concluding remarks
Chapter 4. Banking stem cells for research and clinical applications
2. What are cell banks and why are they important?
3. Banking cells for clinical application
4. Testing and characterization of cell banks
5. The international landscape and cell standardization
6. Conclusions and future perspectives
Chapter 5. Survival, differentiation, and connectivity of ventral mesencephalic dopamine neurons following transplantation
2. Survival of DA neurons in VM grafts
3. Differentiation and composition of VM grafts
4. Connectivity of VM grafts
5. Closing remarks
Chapter 6. Electrophysiological investigations of synaptic connectivity between host and graft neurons
2. The desired functional phenotype: Electrophysiological properties of A9 dopaminergic neurons
3. In vivo versus in vitro grafting schemes
4. Electrophysiological properties of stem cell-derived dopaminergic neurons
5. Maturation versus functional integration
6. Correlations between functional integration and behavioral recovery
7. Pitfalls of assessing functional integration in grafting experiments
8. Concluding remarks and future perspectives
Chapter 7. Nigral grafts in animal models of Parkinson’s disease. Is recovery beyond motor function possible?
2. Nonmotor symptoms in PD: The role of DA
3. Nonmotor symptoms in PD: The restorative capacity of fetal transplants
4. Modeling PD in animals: What have we learned about the role of DA?
5. Nonmotor dysfunction and fetal tissue grafts in rodent models
6. Challenges in the field
Chapter 8. L-DOPA- and graft-induced dyskinesia following transplantation
2. The clinical phenomena of LID
3. Graft-induced dyskinesia
Chapter 9. Current status of clinical trials of neural transplantation in Parkinson’s disease
2. The proof of the concept: Previous trials of fetal neural transplants in PD
3. The state of the art: What have we learned from trials of neural grafting in PD?
4. State of the art: Further considerations in the design of the next generation of neural transplantation trials in PD
5. What do we need to look for? Defining outcome measures for future neural transplantation trials in PD
6. What do natural history studies tell us about relevant outcome measures and end points in clinical trials in PD?
7. The future: The clinical application of SC therapy in PD
Chapter 10. In vivo imaging of the integration and function of nigral grafts in clinical trials
2. Nigral graft survival and relevance to motor symptoms
3. Nigral graft function and DA release
4. Integration of nigral graft with the host brain
5. Graft-induced dyskinesias
6. Patient selection
7. Monoaminergic systems and nonmotor symptoms
8. Inflammatory and immune responses
9. Iron deposition
10. Conclusions and future directions
Chapter 11. Neuropathology in transplants in Parkinson’s disease
2. Parkinson’s disease
3. Neural grafting in Parkinson’s disease
4. Postmortem studies of grafted Parkinson patients
5. Possible mechanisms underlying lewy pathology in grafts
6. Implications of Parkinson-like pathology in grafts for the cell therapy field
7. Concluding remarks
Chapter 12. Derivation of dopaminergic neurons from pluripotent stem cells
2. Why a PSC source?
3. How to define mDA neuron identity from PSC sources?
4. Mouse PSCs
5. Human PSCs
6. Methods of neural induction
7. Rosette-based dopamine neuron differentiation
8. Floor plate-based dopamine neuron differentiation
9. Some of the remaining challenges
Chapter 13. Characterization and criteria of embryonic stem and induced pluripotent stem cells for a dopamine replacement therapy
2. Characterizing human pluripotent stem cell quality and safety for cell therapy in PD
3. The relevance of pluripotent stem cell-derived DA neurons for cell therapy in PD
4. Embryonic stem cells and induced pluripotent stem cells
5. Prioritizing assays to monitor pluripotent stem cell quality
6. Examining chromosomal disruption in pluripotent stem cells
7. Determining genetic mutations in pluripotent stem cells that compromise safety and function of A9 DA neurons
8. Yield of differentiated A9 DA neurons to confirm pluripotent stem cell quality
Chapter 14. Skilled motor control for the preclinical assessment of functional deficits and recovery following nigral and striatal cell transplantation
2. Species similarities
3. Tests of skilled hand use
4. Skilled reaching in experimental models of PD
5. Effects of grafts in experimental models of PD
6. Skilled reaching in experimental models of HD
7. Effects of grafts in experimental models of HD
Chapter 15. Role of experience, training, and plasticity in the functional efficacy of striatal transplants
2. Defining the key factors in the experimental model
3. Experimental support for the role of experience, training, and plasticity in the functional efficacy of striatal transplants
4. Do the experimental data have clinical relevance?
Chapter 16. In vivo imaging of integration and function of striatal grafts in rodent and nonhuman primate animal models
2. Magnetic resonance imaging principles
3. Positron emission tomography
Chapter 17. Clinical trials of neural transplantation in Huntington’s disease
2. Studies leading to clinical transplantation of human striatal cells
3. Principles from preclinical work pertinent to interpreting clinical studies
4. Constraints and design issues of clinical neural transplant studies
5. What has emerged from clinical studies of neural transplantation in HD?
6. What have we learned from postmortem studies?
7. What is the current status of clinical neural transplantation and what are the next steps?
Chapter 18. Derivation of striatal neurons from human stem cells
2. The developing and adult striatum
3. Human stem cell sources for HD cell therapy
4. Telencephalic and striatal differentiation of human pluripotent stem cells
5. Stem cell-derived striatal neurons’ derivation, integration, and function
Other volumes in PROGRESS IN BRAIN RESEARCH
This issue of Progress in Brain Research is split over 2 volumes, bringing together cutting-edge research on functional neural transplantation. The 2 volumes review current knowledge and understanding, provide a starting point for researchers and practitioners entering the field, and build a platform for further research and discovery.
- Leading authors review the state-of-the-art in their field of investigation, and provide their views and perspectives for future research
- Chapters are extensively referenced to provide readers with a comprehensive list of resources on the topics covered
- All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist
Neuroscientists, psychologists, neurologists
- No. of pages:
- © Elsevier 2012
- 11th December 2012
- Hardcover ISBN:
- eBook ISBN:
Dunnett is a behavioural neuroscientist who started a lifelong collaboration with the Björklund team in 1979 to explore the functional consequences of cell transplantation method in animal models of neurodegenerative disease, in particular involving cell replacement and repair of the basal ganglia. He has developed models and novel methods of motor and cognitive assessment to apply behavioural analysis not simply to assess functional efficacy of implanted cells, but as a tool to study the mechanisms of cell integration, circuit reconstruction and functional repair. In parallel his laboratory originated the first UK trial of cell transplantation in Huntington’s disease, and provides the source of clinical grade cells for further ongoing trials in Parkinson’s disease.
Cardiff University, Cardiff, UK
As a neuroanatomist and developmental neurobiologist, during the 1970s Björklund’s lab originated reliable methods for transplantation of embryonic tissues into brain that pioneered practical cell transplantation in the central nervous system, providing the basis for technologies that are now used by laboratories world-wide. In parallel, work in the field has progressed from basic anatomical and developmental studies in experimental animals, via applications for assessing cell replacement and repair using primary and stem cells in the damaged brain, and now underpinning the majority of methods in development for cell therapy in patients. His laboratory continues to analyse the fundamental neurobiology and principles of cell transplantation, regeneration and integration in the CNS, as well as originating the first trials of effective clinical cell transplantation (for Parkinson’s disease) in patients
Lund University, Lund, Sweden