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E-raamat: Functional Neural Transplantation IV: Translation to Clinical Application, Part A

Volume editor (Cardiff University, Cardiff, UK), Volume editor (Lund University, Lund, Sweden)
  • Formaat: PDF+DRM
  • Sari: Progress in Brain Research
  • Ilmumisaeg: 25-May-2017
  • Kirjastus: Academic Press Inc
  • Keel: eng
  • ISBN-13: 9780128118139
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Functional Neural Transplantation IV: Translation to Clinical Application, Part ASuurem pilt
  • Formaat: PDF+DRM
  • Sari: Progress in Brain Research
  • Ilmumisaeg: 25-May-2017
  • Kirjastus: Academic Press Inc
  • Keel: eng
  • ISBN-13: 9780128118139
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Functional Neural Transplantation IV: Translation to Clinical Application, Volume 230 provides a survey of the current status of cell transplantation in the nervous system, with a focus on the conditions for achieving structural repair and functional recovery after brain damage or in neurodegenerative disease.

As the fourth in a periodic series of updates at 5-7 year intervals, this volume highlights recent developments related to the application of advances in cellular and molecular science to an understanding of the fundamental principles of neuroplasticity and regeneration in the brain and spinal cord, also addressing the topic of the power of pluripotent stem cells to generate new sources of precisely specified neurons for utilization in brain repair.

Selected chapters review the latest advances in translating the new technologies to a broader range of neurodegenerative diseases, stroke, spinal cord injury, glial and retinal disease and pain than had hitherto been considered possible, with the realization that the opportunities of off-the-shelf cell therapy may fast be approaching a plausible reality.

  • Comprehensive set of critical reviews covering the field
  • Presents state-of-the-art topics in science and translational medicine
  • Written by international leaders in the field of neural transplantation

Muu info

Focuses on the conditions for achieving structural repair and functional recovery after brain damage or neurodegenerative disease
Contributors v
Preface xv
Chapter 1 Mechanisms and use of neural transplants for brain repair
1(52)
Stephen B. Dunnett
Anders Bjorklund
1 Introduction
2(1)
2 Alternative Mechanisms of Functional Recovery
3(8)
2.1 Nonspecific Mechanisms
6(1)
2.2 "Trophic" Mechanisms
7(2)
2.3 "Bystander" Effects
9(1)
2.4 Circuit Integration
10(1)
3 Transplant-Induced Functional Recovery in Striatal Systems
11(6)
3.1 Integration of Grafted Neurons Into Basal Ganglia Circuitry
11(1)
3.2 Striatal Circuit Reconstruction
12(1)
3.3 Functional Striatal Circuit Repair
13(1)
3.4 Behavioral Evidence for Transplant-Induced Circuitry Repair
14(2)
3.5 Striatal Circuit Plasticity
16(1)
4 Transplant-Induced Recovery in Hippocampus and Cortex Deprived of Their Subcortical Inputs
17(4)
4.1 Transplantation of Septal Cholinergic Neurons to the Deafferented Hippocampus
17(4)
4.2 Transplantation of Basal Forebrain Cholinergic Neurons to the Deafferented Neocortex
21(1)
5 Ability of Grafted Neurons to Regenerate Long-Distance Axonal Pathways
21(5)
5.1 Studies Using GFP Expressing Reporter Mice
22(2)
5.2 Studies Using Cells Derived From Embryonic Stem Cells
24(2)
6 Use of Neural Transplants to Bridge Transecting Lesions in Brain and Spinal Cord
26(6)
7 Prospects for Translation to Clinical Applications
32(21)
Acknowledgments
34(1)
References
35(18)
Chapter 2 Reprogramming of somatic cells: iPS and iN cells
53(16)
Vania Broccoli
1 Optimized Strategies for iPS Cell Reprogramming and High-Quality Validation
54(1)
2 Generation of iNeurons by Direct Cell Conversion
55(6)
2.1 Molecular Mechanisms of Direct Neuronal Reprogramming
56(1)
2.2 Strategies to Improve Efficiency and Maturity of iNeurons
57(2)
2.3 Approaches for the Generation of iNeuronal Subtypes
59(2)
3 Direct Reprogramming of Glial Subtypes
61(1)
4 iNeurons and Glia Cells for Disease in vitro Cell Modeling
62(7)
Acknowledgments
63(1)
References
63(6)
Chapter 3 Brain repair from intrinsic cell sources: Turning reactive glia into neurons
69(30)
Olof Torper
Magdalena Gotz
1 Introduction
69(2)
2 The Road to Direct Neuronal Reprogramming: Learning From Development
71(3)
3 Glial Cells and Reactive Gliosis
74(5)
3.1 Astrocytes and Their Reaction to Injury
74(2)
3.2 NG2 Glia
76(2)
3.3 Microglia
78(1)
4 In Vivo Reprogramming of Endogenous Glial Cells Into Neurons
79(9)
4.1 In Vivo Reprogramming of Proliferating Progenitor Cells by MLV-Based Viral Vectors
79(4)
4.2 In Vivo Reprogramming of Specific and Quiescent Glial Cells
83(1)
4.3 Improving the Efficiency of Neuronal Reprogramming In Vivo
83(3)
4.4 Using Nonintegrating, Recombinant AAVs for Reprogramming
86(1)
4.5 Synaptic Integration of Reprogrammed Neurons
87(1)
5 Future Challenges
88(11)
References
89(10)
Chapter 4 Ex vivo gene therapy for the treatment of neurological disorders
99(34)
Genevieve Gowing
Soshana Svendsen
Clive N. Svendsen
1 Introduction
99(2)
2 Cell Types for ex vivo Gene Therapy
101(1)
3 Strategies to Create Genetically Modified Cells
102(2)
4 Strategies for Delivery
104(1)
5 Ex Vivo Gene Therapy for Specific Neurological Disorders
105(9)
5.1 Alzheimer's Disease
105(2)
5.2 Parkinson's Disease
107(2)
5.3 Amyotrophic Lateral Sclerosis
109(3)
5.4 Huntington's Disease
112(1)
5.5 Stroke
113(1)
6 Challenges and Future Directions for ex vivo Gene Therapy
114(3)
6.1 Regulation of Gene Expression
114(1)
6.2 Tracking of Transplanted Cells
115(1)
6.3 Immune Suppression
116(1)
6.4 Preclinical Study Design for Translation
116(1)
7 Conclusion
117(16)
References
118(15)
Chapter 5 Preparation, characterization, and banking of clinical-grade cells for neural transplantation: Scale up, fingerprinting, and genomic stability of stem cell lines
133(18)
Ammar Natalwala
Tilo Kunath
1 Introduction
134(1)
2 General Overview of clinical-grade Production of a Cell Product
135(1)
3 Manufacturing a Midbrain Dopaminergic Cell Product for Parkinson's
136(9)
3.1 Clinical-Grade hESC and iPSC Lines
136(3)
3.2 Differentiation of mDA Cells---Protocol and Reagents
139(1)
3.3 Characterization for Cell Identity, Safety, and Efficacy
140(1)
3.4 Characterization of Genome and Genomic Stability
141(3)
3.5 Cell Banking and Clinical Delivery of an mDA Cell Product
144(1)
4 Conclusion
145(6)
Acknowledgments
145(1)
References
145(6)
Chapter 6 Regulatory considerations for pluripotent stem cell therapies
151(14)
Melissa K. Carpenter
1 Introduction
151(1)
2 Manufacturing Strategies for PSC-Derived Products
152(1)
2.1 Allogeneic Products
152(1)
2.2 Autologous Products
153(1)
3 Compliance With Regulations
153(4)
3.1 How cGMP Do You Need to Be?
154(1)
3.2 cGTPs and Donor Eligibility
155(1)
3.3 The Choice of Starting Material
156(1)
4 Is Your Stem Cell Therapy Safe and Effective?
157(1)
5 Who Has Done It and What Did They Do?
158(4)
6 Summary and Recommendations
162(3)
References
162(3)
Chapter 7 Strategies for bringing stem cell-derived dopamine neurons to the clinic: A European approach (STEM-PD)
165(26)
Agnete Kirkeby
Malin Parmar
Roger A. Barker
1 Parkinson's Disease and Its Current Treatments
166(1)
2 Cell Replacement Strategies for PD
167(6)
2.1 Graft-Induced Dyskinesias
169(1)
2.2 The TRANSEURO Fetal VM Trial: A Stepping Stone Toward the Next Generation of Stem Cell-Based Trials for PD
170(2)
2.3 Efforts to Expand Human Fetal VM Tissue for Transplantation
172(1)
3 Proof-of-Concept Studies for hESC-Based DA Cell Therapies in Animal Models of PD
173(1)
4 Producing a Cell Product for the STEM-PD Clinical Trial
174(6)
4.1 Choosing the Right Stem Cell Line
174(2)
4.2 Producing a Clinical Cell Product
176(2)
4.3 Defining the Clinical Product Composition
178(1)
4.4 Preclinical Safety and Efficacy Testing
179(1)
5 The STEM-PD Clinical Trial Design
180(5)
5.1 Clinical Transplantation Procedure
180(1)
5.2 Measures to Avoid the Development of GIDs
180(1)
5.3 Clinical Trial Design
181(4)
6 Concluding Remarks: Where Are We Now?
185(6)
References
185(6)
Chapter 8 Strategies for bringing stem cell-derived dopamine neurons to the clinic---The NYSTEM trial
191(22)
Lorenz Studer
1 Introduction
192(1)
2 From Neural Stem Cells to hPSCs and Early Attempts at mDA Neuron Differentiation
193(2)
3 Floor Plate-Based Protocols
195(1)
4 NYSTEM A ward
196(3)
4.1 Introduction
196(1)
4.2 Cell Line Choice
197(1)
4.3 Choice of Cell Media
197(1)
4.4 Choice of Differentiation Protocol
198(1)
4.5 Cryopreservation and Stability
198(1)
4.6 Other Chemistry Manufacturing and Controls Parameters
199(1)
5 Preclinical Validation of the Cell Therapy Product
199(3)
5.1 Early Developmental Studies
199(1)
5.2 Definitive Studies
200(2)
5.3 Nonhuman Primate Studies
202(1)
6 Clinical Planning
202(2)
7 Outlook and Future Developments
204(9)
Acknowledgments
205(1)
References
206(7)
Chapter 9 Strategies for bringing stem cell-derived dopamine neurons to the clinic: The Kyoto trial
213(14)
Jun Takahashi
1 Introduction
213(1)
2 Donor Cells
214(1)
3 Induction and Selection of DA Neurons
215(2)
4 Preclinical Studies
217(1)
5 Optimization of Host Brain Environment
218(2)
6 Tentative Protocol of Clinical Trial
220(1)
7 Conclusion
221(6)
References
222(5)
Chapter 10 From open to large-scale randomized cell transplantation trials in Huntington's disease: Lessons from the multicentric intracerebral grafting in Huntington's disease trial (MIG-HD) and previous pilot studies
227(36)
Anne-Catherine Bachoud-Levi
1 Introduction
228(1)
2 Results From Pilot Trials
229(9)
2.1 Studies Using Small Tissue Blocks for Transplantation
229(6)
2.2 Studies Using Cell Suspensions
235(3)
3 The MIG-HD Trial
238(4)
3.1 The German Extension of the MIG-HD Trial: The Euro-HD Multicenter Study
241(1)
4 Lessons From Published Results: Toward the Design of Future Large-Scale Trials
242(12)
4.1 Design
242(4)
4.2 Procedure
246(4)
4.3 Clinical Assessment
250(4)
5 Conclusions
254(9)
Acknowledgments
255(1)
References
255(8)
Chapter 11 Pluripotent stem cell-derived neurons for transplantation in Huntington's disease
263(20)
Meng Li
Anne E. Rosser
1 Introduction
263(5)
1.1 How Have Fetal Cell Transplants Informed the Way Forward for Pluripotent Cell Implants?
264(3)
1.2 Why Are Pluripotent-Derived Donor Cells Required?
267(1)
1.3 Stem Cells as an Alternative Donor Cells for Therapeutic Transplantation
268(1)
2 Steering PSC Differentiation Into a MSN Fate
268(5)
2.1 General Strategy of PSC Neural Induction
268(1)
2.2 Sonic Approach for Generating MSNs
269(2)
2.3 Induction of MSN Fate via Activin A Signaling
271(2)
3 Generating MSNs From NSCs
273(1)
4 Making MSNs From Somatic Cells by Direct Programming
274(1)
5 Ongoing Challenges
275(1)
6 Conclusion
276(7)
Acknowledgments
276(1)
References
277(6)
Chapter 12 Advanced imaging of transplant survival, fate, differentiation, and integration
283(22)
Nadja Van Camp
Elsa Diguet
Philippe Hantraye
1 Introduction
284(2)
1.1 Role of in vivo Imaging in Cell Therapy
284(1)
1.2 The Concept of "Translational Imaging"
284(1)
1.3 Grafting in a Hostile Environment
285(1)
2 Imaging the Graft
286(10)
2.1 Monitoring in vivo Graft Survival, Development, and Differentiation
286(2)
2.2 Graft Signatures Upon Rejection, Atrophy, or Overgrowth
288(4)
2.3 Imaging Graft Differentiation Through Receptor Expression and Neurotransmitter Production
292(4)
3 Imaging the Host Response
296(3)
4 Conclusion
299(6)
Acknowledgments
300(1)
References
300(5)
Chapter 13 Rehabilitation training in neural restitution
305(26)
Susanne Clinch
Monica Busse
Mate D. Dobrdssy
Stephen B. Dunnett
1 Introduction
306(1)
2 The Role of General Activity in Mediating the Physical Ability of Cells to Survive, Sprout, and Extend Processes
307(2)
3 Training and Exercise Influence Graft Development and Recovery
309(1)
4 Environment-Mediated Morphological Impact on Striatal Grafts
310(1)
5 Importance of Duration and Frequency of Exposure to Enriched Environment
310(1)
6 Electrophysiological Plasticity of Graft-Host Integration
311(2)
7 Do the Experimental Data Have Clinical Relevance?
313(1)
8 Current State of Knowledge in Clinical Populations
314(5)
8.1 Clinical Outcome Measures
314(2)
8.2 Developing Novel Measures for Cell Transplantation
316(3)
9 Rehabilitation Training Strategies for Neural Transplantation
319(2)
10 Concluding Remarks
321(10)
Acknowledgments
322(1)
References
322(9)
Combined Index 331
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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