Frontiers in Brain Repair (eBook)

RAHUL JANDIAL, MD, PhD, is an Assistant Professor in the Division of Neurosurgery, Department of Surgery at City of Hope Comprehensive CancerCenter and the Beckman Research Institute in Los Angeles, California. His clinicalpractice focuses on the surgical and medical care of patients with brain and spinetumors. In the laboratory his team investigates the intersection of stem cell biologyand neuro oncology, specifically identifying the cells from which brain tumors ariseand whether treatment resistant cells can be selectively targeted to help patients livelonger. A prolific author, Jandial has authored/edited 7 books and over 35 papers. Helives with his wife Danielle and their 3 sons Zain, Kai, and Ronak.

Title Page 3
Copyright Page 4
PREFACE 6
ABOUT THE EDITOR... 8
PARTICIPANTS 9
Table of Contents 11
ACKNOWLEDGEMENTS 15
Chapter 1 In Vivo Imaging of Cellular Transplants 16
Introduction 16
Florescent Imaging 16
Quantum Dots 18
PET and SPECT 20
MRI 20
In Vivo Imaging and Tumors 21
In Vivo Imaging and Neurological Disease 23
Conclusion 25
References 26
Chapter 2 Culture and Manipulation of Neural Stem Cells 28
Introduction 28
Neural Stem Cells 29
Defining and Identifying the Neural Stem Cell 29
Genetic Modification of Neural Stem Cells 30
Prodrug Converting Enzyme Strategy 30
Immunomodulatory Strategy 31
Direct Delivery of Cytotoxic Genes 31
Maintaining Neural Stem Cells In Vitro 31
Materials and Methods 32
Materials 32
Methods 33
Maintenance of Human Neural Stem Cells 34
Conclusion 36
References 36
Chapter 3 Animal Models of Neurological Disease 38
Introduction 38
Parkinson’s Disease 38
Reserpine Model 39
Methamphetamine Model 39
6-OHDA Model 40
MPTP Model 41
Rotenone Model 44
Genetic Models 44
Cerebral Ischemia 44
Focal Cerebral Ischemia Models 45
Global Cerebral Ischemia Models 46
Huntington’s Disease 47
Mouse Models of HD 47
Other Models 48
Alzheimer’s Disease 48
APP Transgenic Mouse Models 49
Tau Transgenic Mouse Models 50
Conclusion 50
References 51
Chapter 4 Stem Cell Transplantation Methods 56
Introduction 56
Factors 58
Choosing the Ideal Cell Source 58
Adult Neural Stem Cells 58
Embryonic Stem Cells 59
Method of NSC Isolation 60
Preparing NSCs before Transplant 60
Choosing the Experimental Animal 61
Choosing the Surgical Procedure 62
Potential Routes of NSC Administration 62
Neonatal 64
Midgestational In Utero 64
Adult 64
Considerations during Surgery 66
Postoperative Care 67
Optimization 67
Anticipated Results and Methods of Detection 68
Conclusion 69
References 69
Chapter 5 Stem Cell Origin of Brain Tumors 73
Introduction 73
Reappraising the Prevailing Theory of Tumor Genesis 74
Evidence for NSC as the Cell of Origin 75
NSCs and Gliomas Share Histological and Biological Similarities 75
NSCs More Likely to Accumulate Oncogenic Mutations 75
Cancer Stem Cells 77
Gliomas and NSCs Have Common Regulatory Pathways 79
Mouse Models of Gliomas for Investigation of Glioma Origin 79
Conclusion 79
References 80
Chapter 6 The Tumor Microenvironment 82
Introduction 82
Prevailing Theory of Tumor Initiation 83
Cancer Stem Cells—Discovery and Evidence of BTSC 83
Caveats to BTSC 85
The Tumor Microenvironment 86
Conclusion 87
References 88
Chapter 7 Exploitation of Genetically Modified Neural Stem Cells for Neurological Disease 89
Exploiting NSCs for Therapeutic Transplantation 89
Genetically Modified NSCs and Neurological Disease 91
Neurodegenerative Disorders 93
Brain Tumors 95
Spinal Cord Injury 97
Stroke 98
Enzyme Delivery in Lysosomal Storage Diseases 99
The Aging Brain 101
In Vivo Imgaging of Transplanted NSCs 101
Conclusion 104
References 105
Chapter 8 Biological Horizons for Targeting Brain Malignancy 108
Introduction 108
Neural Stem Cells 109
Exogenous and Endogenous NSCs Respond to Gliomas 110
Mechanisms for NSC Homing to Gliomas 110
Exploiting NSCs as Vehicles for Delivering Toxic Payloads 111
Conclusion 113
References 114
Chapter 9 Stem Cells in the Treatment of Stroke 120
Introduction 120
Stem Cell Therapy 121
Stem Cell Biology—In Vitro 121
Stem Cell Biology and Animal Models 123
Cellular Reconstitution of Stroke Lesions 125
Stroke Treatment Via Enhanced Trophic Factor Delivery 126
The Potential of Cord Blood 126
Conclusion 128
References 128
Chapter 10 Gene- and Cell-Based Approaches for Neurodegenerative Disease 132
Introduction 132
Cellular and Molecular Pathophysiology of Alzheimer’s Disease 133
Cellular and Molecular Pathophysiology of Parkinson’s Disease 134
Cellular and Molecular Pathophysiology of Huntington’s Disease 136
Stem Cell Therapy for Neurodegenerative Diseases 136
Immunotherapy and Alzheimer’s Disease 137
Gene-Based Approaches to Therapy 140
Conclusion 141
References 141
INDEX 146