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E-raamat: Functional Neural Transplantation III: Primary and Stem Cell Therapies for Brain Repair, Part I

Volume editor (Lund University, Lund, Sweden), Volume editor (Cardiff University, Cardiff, UK)
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  • Sari: Progress in Brain Research
  • Ilmumisaeg: 31-Dec-2012
  • Kirjastus: Elsevier Science Ltd
  • Keel: eng
  • ISBN-13: 9780444595881
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Functional Neural Transplantation III: Primary and Stem Cell Therapies for Brain Repair, Part ISuurem pilt
  • Formaat: EPUB+DRM
  • Sari: Progress in Brain Research
  • Ilmumisaeg: 31-Dec-2012
  • Kirjastus: Elsevier Science Ltd
  • Keel: eng
  • ISBN-13: 9780444595881
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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

Muu info

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
Contributors v
SECTION 1 INTRODUCTION
Chapter 1 Introduction (Part I)
3(4)
Stephen B. Dunnett
Anders Bjorklund
Chapter 2 Transplantation in the Future
7(10)
Fred H. Gage
1 Constraints
8(3)
1.1 Role of the Cellular Graft
8(1)
1.2 Temporal Features of the Disease Model
8(1)
1.3 Safety
8(1)
1.4 Donor Cell Type: Current
9(1)
1.5 State of the Host Upon Implantation
10(1)
2 Future Directions
11(6)
2.1 Cellular Transplants to Study Human Disease
11(1)
2.2 Synthetic, Bioengineered Cells
12(5)
SECTION 2 CHALLENGES BRINGING CELL THERAPIES TO THE CLINIC
Chapter 3 Ethical Challenges for Using Human Cells in Clinical Cell Therapy
17(24)
Goran Hermeren
1 Introduction
17(1)
2 Challenges, Ethical, and Others
18(2)
2.1 Economic, Legal, and Ethical Concerns
18(1)
2.2 Traditional Ethical Challenges
18(1)
2.3 More Recent Ethical Challenges
19(1)
3 Scientific Challenges and Ethics
20(3)
3.1 Ethics and the Direction of Applied Research
20(1)
3.2 Conceptions of Science
21(1)
3.3 General Scientific Challenges Facing SC Research
21(1)
3.4 Science and Ethics
22(1)
4 Societal Concerns: Legal and Economic Issues
23(4)
4.1 Legal Challenges
24(1)
4.2 Economic Concerns and Ethics
25(1)
4.3 Hype, Media, and Funding Policy
26(1)
5 Meeting Ethical Challenges and Three Theses
27(3)
5.1 Identifying and Clarifying Ethical Challenges
27(1)
5.2 Consequentialist and Deontological Traditions
28(1)
5.3 Implications and Controversies
29(1)
5.4 Three Theses
30(1)
6 Stages and Stage-Related Challenges
30(6)
6.1 Translation and Stages
30(1)
6.2 Stage-Related Challenges
31(3)
6.3 Precaution and Decision Making
34(1)
6.4 In Concluding, a Fourth Thesis: The Need to be Specific
35(1)
7 Concluding Remarks
36(5)
References
36(5)
Chapter 4 Banking Stem Cells for Research and Clinical Applications
41(20)
Glyn Stacey
1 Introduction
42(1)
2 What are Cell Banks and Why are they Important?
42(2)
3 Banking Cells for Clinical Application
44(6)
3.1 Translating Donor Tissues to Research or Human Application
44(1)
3.2 What is a Clinical Grade Cell Bank?
45(1)
3.3 Cell Line Derivation and Culture, and Science-Based Risk Assessment
46(2)
3.4 Banking Facilities and Processes
48(2)
4 Testing and Characterization of Cell Banks
50(3)
4.1 Cell Authenticity
51(1)
4.2 Viability
51(1)
4.3 Microbial Contamination
52(1)
4.4 Genetic Stability
53(1)
5 The International Landscape and Cell Standardization
53(1)
6 Conclusions and Future Perspectives
54(7)
References
55(6)
SECTION 3 DOPAMINE SYSTEMS
Chapter 5 Survival, Differentiation, and Connectivity of Ventral Mesencephalic Dopamine Neurons Following Transplantation
61(36)
Lachlan Thompson
Anders Bjorklund
1 Introduction
62(2)
2 Survival of DA Neurons in VM Grafts
64(6)
2.1 Donor Age of VM Preparations
65(2)
2.2 Tissue Handling
67(2)
2.3 Host-Specific Variables Affect VM Graft Survival
69(1)
3 Differentiation and Composition of VM Grafts
70(6)
3.1 Nondopaminergic Cells in VM Grafts
70(3)
3.2 Midbrain DA Neuron Subtypes in VM Grafts
73(3)
4 Connectivity of VM Grafts
76(9)
4.1 Variables Affecting Outgrowth of DA Neurons
77(2)
4.2 Host-Derived Afferent Connectivity with Intrastriatal VM Grafts
79(1)
4.3 Cell-type Specificity of Efferent Outgrowth from Intrastriatal VM Grafts
79(3)
4.4 Connectivity of Intranigral VM Grafts
82(3)
5 Closing Remarks
85(12)
References
86(11)
Chapter 6 Electrophysiological Investigations of Synaptic Connectivity Between Host and Graft Neurons
97(16)
Jan Tønnesen
Merab Kokaia
1 Introduction
98(1)
2 The Desired Functional Phenotype: Electrophysiological Properties of A9 Dopaminergic Neurons
99(2)
3 In vivo Versus In vitro Grafting Schemes
101(1)
4 Electrophysiological Properties of Stem Cell-Derived Dopaminergic Neurons
102(2)
5 Maturation Versus Functional Integration
104(3)
6 Correlations Between Functional Integration and Behavioral Recovery
107(1)
7 Pitfalls of Assessing Functional Integration in Grafting Experiments
107(2)
8 Concluding Remarks and Future Perspectives
109(4)
References
109(4)
Chapter 7 Nigral Grafts in Animal Models of Parkinson's Disease. Is Recovery Beyond Motor Function Possible?
113(30)
Mariah J. Lelos
Eilis Dowd
Stephen B. Dunnett
1 Introduction
114(2)
2 Nonmotor Symptoms in PD: The Role of DA
116(2)
3 Nonmotor Symptoms in PD: The Restorative Capacity of fetal Transplants
118(1)
4 Modeling PD in Animals: What Have We Learned About the Role of DA?
119(2)
5 Nonmotor Dysfunction and Fetal Tissue Grafts in Rodent Models
121(7)
6 Challenges in the Field
128(5)
6.1 Development of Animal Models of PD
129(1)
6.2 Sensitive Behavioral Assays
129(1)
6.3 Aspects of Behavioral Dysfunction Resistant to Graft-Induced Recovery
130(1)
6.4 Cell Replacement Therapy Versus Pharmaceutical Intervention
131(1)
6.5 Primary Fetal Tissue Versus Stem Cell Therapies
131(2)
7 Conclusions
133(10)
Acknowledgments
133(1)
References
133(10)
Chapter 8 L-DOPA- and Graft-Induced Dyskinesia Following Transplantation
143(26)
Emma L. Lane
Christian Winkler
1 Introduction
143(2)
1.1 The Problem of Dyskinesia in Parkinson's Disease and Cell Transplantation
143(2)
2 The Clinical Phenomena of LID
145(7)
2.1 Preclinical Models of LID
146(1)
2.2 The Effect of Transplantation on LID
146(4)
2.3 Serotonin and LID
150(2)
3 Graft-Induced Dyskinesia
152(8)
3.1 The Clinical Phenomena of GID
152(1)
3.2 Animal Models of GID
152(2)
3.3 Patient Selection
154(1)
3.4 Dopamine Receptors and GID
155(1)
3.5 Graft Location and Composition and GID
156(3)
3.6 Inflammation and GID
159(1)
3.7 α-Synuclein and GID
160(1)
4 Conclusion
160(9)
Acknowledgments
161(1)
References
161(8)
Chapter 9 Current Status of Clinical Trials of Neural Transplantation In Parkinson's Disease
169(30)
Jonathan R. Evans
Sarah L. Mason
Roger A. Barker
1 Introduction
170(1)
2 The Proof of the Concept: Previous Trials of Fetal Neural Transplants in PD
171(3)
3 The State of the Art: What Have We Learned from Trials of Neural Grafting in PD?
174(4)
3.1 Surgical Aspects
174(1)
3.2 Medical Aspects
175(3)
4 State of the Art: Further Considerations in the Design of the Next Generation of Neural Transplantation Trials in PD
178(2)
4.1 Ethical Considerations
178(2)
5 What do We Need to Look for? Defining Outcome Measures for Future Neural Transplantation Trials in PD
180(4)
5.1 Neuroimaging in PD Neural Transplantation Trials
180(2)
5.2 Clinical End Points in PD Transplantation Trials and the Concept of Disease Modification
182(2)
6 What do Natural History Studies Tell us About Relevant Outcome Measures and End Points in Clinical Trials in PD?
184(2)
7 The Future: The Clinical Application of SC Therapy in PD
186(3)
7.1 TRANSEURO
187(2)
8 Conclusion
189(10)
References
191(8)
Chapter 10 In vivo Imaging of the Integration and Function of Nigral Grafts in Clinical Trials
199(22)
Marios Poiitis
Paola Piccini
1 Introduction
200(1)
2 Nigral Graft Survival and Relevance to Motor Symptoms
201(4)
3 Nigral Graft Function and DA Release
205(1)
4 Integration of Nigral Giaft with the Host Brain
206(3)
4.1 Brain Activation During Movement
206(1)
4.2 Structural Connectivity
207(1)
4.3 Functional Connectivity
208(1)
5 Graft-Induced Dyskinesias
209(2)
6 Patient Selection
211(1)
7 Monoaminergic Systems and Nonmotor Symptoms
211(2)
8 Inflammatory and Immune Responses
213(1)
9 Iron Deposition
213(1)
10 Conclusions and Future Directions
214(7)
Acknowledgments
214(1)
References
215(6)
Chapter 11 Neuropathology in Transplants in Parkinson's Disease: Implications for Disease Pathogenesis and the Future of Cell Therapy
221(22)
Patrik Brundin
Jeffrey H. Kordower
1 Introduction
222(2)
2 Parkinson's Disease
224(1)
3 Neural Grafting in Parkinson's Disease
225(1)
4 Postmortem Studies of Grafted Parkinson Patients
226(6)
4.1 Survival of Grafted Dopaminergic Neurons
226(1)
4.2 Lewy Bodies in Grafted Neurons
226(2)
4.3 Does the Parkinson's Disease Pathogenesis Really Attack the Grafted Neurons?
228(4)
5 Possible Mechanisms Underlying Lewy Pathology in Grafts
232(4)
5.1 Neuroinflammation
232(1)
5.2 Oxidative Stress and Excitotoxicity
233(1)
5.3 Prion-like Behavior of α-Synuclein
234(2)
6 Implications of Parkinson-like Pathology in Grafts for the Cell Therapy Field
236(1)
7 Concluding Remarks
237(6)
Acknowledgments
237(1)
References
238(5)
Chapter 12 Derivation of Dopaminergic Neurons from Pluripotent Stem Cells
243(22)
Lorenz Studer
1 Introduction
244(1)
2 Why a PSC Source?
245(1)
3 How to Define mDA Neuron Identity from PSC Sources?
246(1)
4 Mouse PSCs
247(3)
5 Human PSCs
250(1)
6 Methods of Neural Induction
251(1)
7 Rosette-Based Dopamine Neuron Differentiation
252(1)
8 Floor Plate-Based Dopamine Neuron Differentiation
252(2)
9 Some of the Remaining Challenges
254(11)
References
256(9)
Chapter 13 Characterization and Criteria of Embryonic Stem and Induced Pluripotent Stem Cells for a Dopamine Replacement Therapy
265(14)
Oliver Cooper
Malin Parmar
Ole Isacson
1 Introduction
266(1)
2 Characterizing Human Pluripotent Stem Cell Quality and Safety for Cell Therapy in PD
266(2)
3 The Relevance of Pluripotent Stem Cell-Derived Da Neurons for Cell Therapy in PD
268(1)
4 Embryonic Stem Cells and Induced Pluripotent Stem Cells
268(1)
5 Prioritizing Assays to Monitor Pluripotent Stem Cell Quality
269(1)
6 Examining Chromosomal Disruption in Pluripotent Stem Cells
269(1)
7 Determining Genetic Mutations in Pluripotent Stem Cells that Compromise Safety and Function of A9 DA Neurons
270(1)
8 Yield of Differentiated A9 DA Neurons to Confirm Pluripotent Stem Cell Quality
270(1)
9 Conclusion
271(8)
Acknowledgments
272(1)
References
272(7)
SECTION 4 STRIATAL SYSTEMS
Chapter 14 Skilled Motor Control for the Preclinical Assessment of Functional Deficits and Recovery Following Nigral and Striatal Cell Transplantation
279(24)
Alexander Klein
Ian Q. Whishaw
1 Introduction
280(2)
2 Species Similarities
282(1)
3 Tests of Skilled Hand Use
282(5)
4 Skilled Reaching in Experimental Models of PD
287(1)
5 Effects of Grafts in Experimental Models of PD
287(3)
6 Skilled Reaching in Experimental Models of HD
290(1)
7 Effects of Grafts in Experimental Models of HD
291(1)
8 Conclusions
292(11)
Acknowledgments
293(1)
References
293(10)
Chapter 15 Role of Experience, Training, and Plasticity in the Functional Efficacy of Striatal Transplants
303(26)
Mate D. Dobrossy
Guido Nikkhah
1 Introduction
303(3)
1.1 Can the Properties of the Graft be Modified Following Transplantation?
304(1)
1.2 Cellular and Biochemical Plasticity of the Adult Host and Embryonic Striatal Grafts
305(1)
2 Defining the Key Factors in the Experimental Model
306(4)
2.1 The Animal Model; Lesion, Transplantation, Repair, and Recovery
306(3)
2.2 Defining "Training and Activity"
309(1)
2.3 Defining Environmental Enrichment
309(1)
3 Experimental Support for the Role of Experience, Training, and Plasticity in the Functional Efficacy of Striatal Transplants
310(10)
3.1 Can Training and Experience Affect Graft-Mediated Behavioral Recovery?
310(1)
3.2 "Learning to Use the Graft" in the Striatal Graft Model
311(1)
3.3 Unraveling the Nature of the Motor Training Necessary to Promote the Striatal Graft-Mediated Functional Recovery
312(3)
3.4 Environment-Mediated Morphological Impact on Striatal Grafts
315(1)
3.5 Electrophysiological Assessment of Graft-Host Integration: Bidirectional Synaptic Plasticity in the Striatal Grafts
316(2)
3.6 Electrophysiological Assessment of Graft-Host Integration: Environmental Enrichment Stimulates Striatal BDNF Release and Facilitates LTP in Striatal Grafts
318(1)
3.7 Importance of Duration and Frequency of Exposure to Enriched Environment
319(1)
4 Do the Experimental Data Have Clinical Relevance?
320(1)
5 Conclusion
321(8)
References
321(8)
Chapter 16 In vivo Imaging of Integration and Function of Striatal Grafts in Rodent and Nonhuman Primate Animal Models
329(16)
Philippe Hantraye
Romina Aron Badin
1 Introduction
330(1)
1.1 The Use of Cell Therapy in Brain Disorders
330(1)
1.2 Imaging of Cell Therapy
330(1)
2 Magnetic Resonance Imaging Principles
330(5)
2.1 MRI Applications
332(2)
2.2 MRS Applications
334(1)
3 Positron Emission Tomography
335(4)
3.1 PET Markers of Striatal Deficiency
335(1)
3.2 Striatal Graft Imaging
336(3)
4 Conclusion
339(6)
Acknowledgments
340(1)
References
340(5)
Chapter 17 Clinical Trials of Neural Transplantation in Huntington's Disease
345(28)
Anne E. Rosser
Anne-Catherine Bachoud-Levi
1 Introduction
345(2)
2 Studies Leading to Clinical Transplantation of Human Striatal Cells
347(1)
3 Principles from Preclinical Work Pertinent to Interpreting Clinical Studies
347(3)
3.1 What are the Optimal Donor Cells?
347(1)
3.2 Graft Integration
348(1)
3.3 Scaling up for Human Studies
349(1)
4 Constraints and Design Issues of Clinical Neural Transplant Studies
350(7)
4.1 Donor Tissue
354(2)
4.2 Clinical Outcome Measures
356(1)
4.3 Regulation
357(1)
5 What has Emerged from Clinical Studies of Neural Transplantation in HD?
357(4)
6 What Have We Learned from Postmortem Studies?
361(2)
7 What is the Current Status of Clinical Neural Transplantation and what are the Next Steps?
363(10)
References
365(8)
Chapter 18 Derivation of striatal Neurons from Human Stem Cells
373(32)
Pedro Viegas
Camille Nicoleau
Anselme L. Perrier
1 Introduction
374(1)
2 The Developing and Adult Striatum
375(6)
2.1 The Striatum: Structure, Functions, and Cellular Composition
375(2)
2.2 Forebrain Ontogenesis
377(2)
2.3 Striatal Ontogenesis
379(1)
2.4 Striatal Diseases
380(1)
2.5 Fetal Cell Therapy for Huntington's Disease
380(1)
3 Human Stem Cell Sources for HD Cell Therapy
381(3)
4 Telencephalic and Striatal Differentiation of Human Pluripotent Stem Cells
384(7)
4.1 Patterning Signals for In Vitro Differentiation Protocols
384(4)
4.2 Retinoic Acid
388(1)
4.3 Fibroblast Growth Factors
388(1)
4.4 Wnt/β-Catenin Signals
389(1)
4.5 BMP/TGFβ Signals
390(1)
4.6 SHH Signals
390(1)
5 Stem Cell-derived Striatal Neurons' Derivation, Integration, and Function
391(2)
6 Conclusion
393(12)
Acknowledgments
393(1)
References
393(12)
Combined Index 405(14)
Other Volumes In Progress In Brain Research 419
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 Huntingtons disease, and provides the source of clinical grade cells for further ongoing trials in Parkinsons disease. As a neuroanatomist and developmental neurobiologist, during the 1970s Björklunds 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 Parkinsons disease) in patients
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