Jr / Jr. Progenitor Cell Therapy for Neurological Injury

1. Auflage 2010
ISBN: 978-1-60761-965-9
Verlag: Humana Press
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 200 Seiten

There are currently no reparative therapies for severe neurological injury, including brain injury, spinal cord injury and stroke. Actually, most treatments are designed simply to limit secondary damage. However, pre-clinical data supports the idea that exogenous stem and progenitor cells have the potential to promote a reparative response to severe neurological injuries. Progenitor Cell Therapy for Neurological Injury is a compilation of seminal essays that explore many unique aspects of neurological injury, focusing on the critical translational issues of cell delivery. Specifically, it discusses routes of administration, types of progenitor cells (alone and/or in combinations), timing of delivery and adjuncts to promote cell engraftment, survival and effectiveness. In addition, many chapters address measuring the effects of transplanted cells and cell tracking. The paradigms of how cell-based therapeutics affect neurological injury is changing rapidly. The developments in this field may ultimately offer realistic hope for improvement in patients with severe injuries. This book is a vital key toward unlocking those future treatments.

Autoren/Hrsg.

Jr,

Jr.,

Inhaltsverzeichnis

1;Preface;6
2;Contents;8
3;Contributors;10
4;Chapter 1: Basics of Stem and Progenitor Cells;12
4.1;1.1 Speaking the “Stem Cell Language”: Definitions and Criteria;13
4.2;1.2 Adult Stem Cells;14
4.2.1;1.2.1 Bone Marrow-Derived Cell Populations;15
4.2.1.1;1.2.1.1 Mesenchymal Stromal Cells;15
4.2.1.2;1.2.1.2 Multipotent Adult Progenitor Cells;16
4.2.1.3;1.2.1.3 Hematopoietic Stem Cells;16
4.2.1.4;1.2.1.4 Mononuclear Cells;17
4.2.2;1.2.2 Nervous System-Derived Cell Populations;17
4.2.2.1;1.2.2.1 Neural Stem Cells;17
4.2.3;1.2.3 Other Niche-Derived Adult Stem Cell Populations;19
4.2.3.1;1.2.3.1 Umbilical Cord Blood and Umbilical Cord Matrix Stroma Stem/Progenitor Cells;19
4.2.3.2;1.2.3.2 Embryonic Stem Cells;19
4.3;1.3 Nuclear Reprogramming;20
4.3.1;1.3.1 Induced Pluripotent Stem Cells;21
4.3.2;1.3.2 Somatic Cell Nuclear Transfer, Cellular Fusion, and Exposure to Cellular Extract;21
4.4;1.4 Interaction Between the Cell and the Immune System;22
4.5;1.5 The Age of the Isolated Cell;23
4.6;1.6 The Importance of Critical Examination of the Stem/Progenitor Cell Population and Concluding Remarks;25
4.7;References;25
5;Chapter 2: Progenitor Cell Tissue Engineering;30
5.1;2.1 Introduction;31
5.2;2.2 Tissue Scaffold Goals;32
5.2.1;2.2.1 High Surface Area-to-Volume Ratio;33
5.2.2;2.2.2 Suitable Microenvironment;33
5.2.3;2.2.3 Appropriate Biomaterial;35
5.2.4;2.2.4 Brain-Specific Considerations;36
5.3;2.3 Fabrication of Tissue Scaffolds;37
5.3.1;2.3.1 Thermally Induced Phase Separation;38
5.3.1.1;2.3.1.1 Solid–Liquid Phase Separation;38
5.3.1.2;2.3.1.2 Liquid–Liquid Phase Separation;39
5.3.2;2.3.2 Leaching;40
5.3.3;2.3.3 Electrospinning;40
5.3.3.1;2.3.3.1 System Overview;40
5.3.3.2;2.3.3.2 Process Conditions;42
5.3.3.2.1;Electric Field;43
5.3.3.2.2;Field Strength;43
5.3.3.2.3;Field Shape;43
5.3.3.2.4;Structure;43
5.3.3.2.5;Solution Flow Rate;44
5.3.3.3;2.3.3.3 Material Solution Properties;44
5.3.3.3.1;Polymer Selection;44
5.3.3.3.2;Molecular Weight;44
5.3.3.3.3;Solvent Selection;45
5.3.3.3.4;Solution Concentration;45
5.3.3.4;2.3.3.4 Central Nervous System-Based Applications;45
5.3.4;2.3.4 Rapid Prototyping;47
5.3.4.1;2.3.4.1 Selective Laser Sintering;48
5.3.4.2;2.3.4.2 3D Printing/Inkjet Deposition;49
5.3.4.3;2.3.4.3 BioPlotting/Fused Deposition Modeling;50
5.3.4.4;2.3.4.4 Stereolithography;51
5.4;2.4 Conclusion;52
5.5;References;53
6;Chapter 3: Stem Cell Delivery Methods and Routes;58
6.1;3.1 Current Delivery Vehicles;59
6.1.1;3.1.1 Intravenous Infusion;59
6.1.2;3.1.2 Intra-arterial Infusion;66
6.1.3;3.1.3 Direct Implantation;69
6.1.4;3.1.4 Intrathecal Injection;70
6.2;3.2 Novel Delivery Methods/Vehicles;71
6.2.1;3.2.1 Scaffold Constructs;71
6.2.2;3.2.2 Hydrogels;72
6.2.3;3.2.3 Enhancement of Progenitor Engraftment;73
6.2.3.1;3.2.3.1 Effects of Age/Number of Cells Infused;73
6.2.3.2;3.2.3.2 Homing Receptors;73
6.2.3.3;3.2.3.3 Hypoxia;73
6.2.3.4;3.2.3.4 Toll-Like Receptors;74
6.3;3.3 Barriers to Cell Therapy: Effect of Catheter Infusion;74
6.4;3.4 Future Considerations;75
6.5;References;76
7;Chapter 4: Neural Progenitor Cells for Traumatic Brain and Spinal Cord Injury: Endogenous Cell Rescue Versus Replacement Mechanisms;80
7.1;4.1 Introduction;81
7.2;4.2 Central Nervous System Cell Types or Relationships to Injury and Progenitor Cell Therapy;81
7.2.1;4.2.1 Astrocytes;81
7.2.2;4.2.2 Oligodendrocytes;82
7.2.3;4.2.3 Microglia;82
7.2.4;4.2.4 Endothelial Cells and Pericytes;84
7.2.5;4.2.5 Neural Progenitor Cells;84
7.3;4.3 Traumatic Brain Injury: Effects on Endogenous and Transplanted Neural Stem Cells;87
7.3.1;4.3.1 Endogenous Neural Stem Cells;87
7.3.2;4.3.2 Transplanted Neural Stem Cells;88
7.4;4.4 Spinal Cord Injury: Effects of Endogenousand Transplanted Neural Stem Cells;91
7.4.1;4.4.1 Endogenous Neural Stem Cells;91
7.4.1.1;4.4.1.1 Modulation of Cytokines/Growth Factors: Potential Approach to Modify Injury Response/Progenitor Cell Proliferation;92
7.4.1.2;4.4.1.2 Growth Factor/Genetic Manipulation;92
7.4.1.3;4.4.1.3 Other Mechanisms;93
7.4.2;4.4.2 Neural Stem Cell Transplantation;93
7.4.2.1;4.4.2.1 Timeline for Transplantation;94
7.4.2.2;4.4.2.2 Embryonic/Fetal-Derived Neural Stem Cells;94
7.4.2.3;4.4.2.3 Adult Neural Stem Cells;98
7.5;4.5 Discussion;101
7.6;References;101
8;Chapter 5: Traumatic Brain Injury Pathophysiology/Models;107
8.1;5.1 Traumatic Brain Injury Classification;108
8.2;5.2 Traumatic Brain Injury Pathophysiology:Implications for Future Targets;110
8.2.1;5.2.1 Post-injury Neural Excitotoxicity;111
8.2.2;5.2.2 Cerebral Edema;112
8.2.3;5.2.3 Mitochondrial Injury;113
8.2.4;5.2.4 Neuronal Inflammation;113
8.3;5.3 In Vivo Models;115
8.3.1;5.3.1 Direct Impact Injury;116
8.3.1.1;5.3.1.1 Fluid Percussion Injury;116
8.3.1.2;5.3.1.2 Controlled Cortical Impact Injury;117
8.3.1.3;5.3.1.3 Focal Cortical Compression;120
8.3.2;5.3.2 Non-impact Acceleration Injury;121
8.3.3;5.3.3 Blast-Induced Neurotrauma;121
8.4;5.4 Cell Therapy;122
8.4.1;5.4.1 Clinical Significance;122
8.4.2;5.4.2 Possible Therapeutic Mechanisms;123
8.4.3;5.4.3 Barriers to Treatment;125
8.4.3.1;5.4.3.1 Effect of Elevated Serum Osmolarities;125
8.4.3.2;5.4.3.2 Emboli and Tumor Development;126
8.5;5.5 Future Considerations;127
8.6;References;127
9;Chapter 6: Traumatic Brain Injury: Relationshipof Clinical Injury to Progenitor Cell Therapeutics;133
9.1;6.1 Introduction;134
9.1.1;6.1.1 Adult Versus Pediatric TBI: Pathophysiological Differences;137
9.1.2;6.1.2 Epidural Hematomas;138
9.1.3;6.1.3 Subdural Hematomas;138
9.1.4;6.1.4 Edema/Shearing;138
9.2;6.2 Pathophysiology as Linked to Progenitor Cells;139
9.3;6.3 Applications of Preclinical Data;140
9.3.1;6.3.1 Potential Mechanisms of Action for Adult Progenitor Cell Treatment of Traumatic Brain Injury: Bone Marrow Mononuclear Cell, Mesenchymal Stromal Cell, Multipotent Adult Progenitor Cell, Human Umbilical Cord Blood, and Derivatives ;140
9.4;6.4 Outcomes Measures;142
9.4.1;6.4.1 Functional;142
9.4.2;6.4.2 Structural Correlates to Functional Outcome Measures;143
9.4.2.1;6.4.2.1 Initial Imaging;143
9.4.2.2;6.4.2.2 Options for Structural Analyses;145
9.5;6.5 Regulatory Aspects/Logistical Considerations of Progenitor Cell Therapy for TBI;146
9.5.1;6.5.1 Regulatory Issues;146
9.5.2;6.5.2 Informed Consent;149
9.5.3;6.5.3 Language;149
9.5.4;6.5.4 Coordination;149
9.5.5;6.5.5 Infrastructure Requirements;149
9.6;6.6 Current and Future Studies;150
9.7;References;151
10;Chapter 7: Cell-Based Therapy for Stroke;153
10.1;7.1 Introduction;154
10.2;7.2 Cell Types and Sources;155
10.2.1;7.2.1 Neural Stem Cells;155
10.2.1.1;7.2.1.1 Human Embryonic Stem Cell-Derived Neural Stem Cells;155
10.2.1.2;7.2.1.2 Human Fetal-Derived Neural Stem Cells;155
10.2.1.3;7.2.1.3 Cell Lines;155
10.2.2;7.2.2 Non-neural Stem Cells;156
10.2.2.1;7.2.2.1 Adipose Tissue Mesenchymal Progenitor Cells;156
10.2.2.2;7.2.2.2 Bone Marrow Mesenchymal Stem Cells;156
10.2.2.3;7.2.2.3 Umbilical Cord Blood Cells;157
10.2.2.4;7.2.2.4 Bone Marrow-Derived Mononuclear Cells;157
10.2.2.5;7.2.2.5 Peripheral Blood Progenitor Cells and Peripherally Derived Mononuclear Cells;157
10.3;7.3 Possible Mechanisms of Cellular Therapy;157
10.4;7.4 Key Translational Barriers to AdministeringCells as a Therapy for Stroke;159
10.4.1;7.4.1 Cell Tracking and Imaging;159
10.5;7.5 Potential Risks of Stem Cell Therapy;160
10.6;7.6 Routes of Stem Cell Delivery;160
10.6.1;7.6.1 Intracerebral Delivery;160
10.6.2;7.6.2 Intracerebroventricular/Intracisternal Delivery;161
10.6.3;7.6.3 Intravenous Delivery;161
10.6.4;7.6.4 Intra-arterial Delivery;162
10.7;7.7 Dose of Stem Cells;162
10.8;7.8 Timing of Stem Cell Delivery;163
10.9;7.9 Clinical Trials;163
10.10;7.10 STEPS Guidelines;165
10.11;References;165
11;Chapter 8: Spinal Cord Injury Pathophysiology and Progenitor Cell Therapy;172
11.1;8.1 Introduction;173
11.2;8.2 Economics;174
11.3;8.3 Pediatric Versus Adult Spinal Cord Injury;174
11.3.1;8.3.1 Biomechanical Considerations;174
11.3.2;8.3.2 Age and Injury Pattern;176
11.3.3;8.3.3 Outcome;177
11.4;8.4 Biochemical and Cellular Sequela of Spinal Cord Injury;177
11.5;8.5 Immune System Response to Spinal Cord Injury;178
11.6;8.6 Intrinsic Spinal Cord Repair Potential;180
11.7;8.7 Preclinical Spinal Cord Injury Progenitor Cell Experience;180
11.7.1;8.7.1 Replace Missing Myelin-Forming Cells;180
11.7.2;8.7.2 Replace Missing Neurons;181
11.7.3;8.7.3 Support Endogenous Spinal Cord Repair;181
11.7.4;8.7.4 Modulate Immune Response to Enhance Repair;181
11.7.5;8.7.5 Biomatrix Studies;182
11.7.6;8.7.6 Experimentally Induced Allodynia;182
11.8;8.8 Human Spinal Cord Injury Stem Cell Trials;183
11.8.1;8.8.1 Human Trials Using Autologous Bone Marrow-Derived Mononuclear Cells Delivered by Intravenous or Intra-arterial Infusion;183
11.8.2;8.8.2 Human Trials Using Autologous Bone Marrow-Derived Mononuclear Cells Delivered by Lumbar Puncture;184
11.8.3;8.8.3 Human Trials Using Bone Marrow-Derived Mononuclear Cells Delivered by Direct Injection or Surgical Implantation into the Injured Spinal Cord;185
11.8.4;8.8.4 Human Trials Using Embryonically Derived Stem Cell Products;185
11.9;8.9 Conclusion;186
11.10;References;186
12;Chapter 9: Progenitor Cell Therapy for the Treatment of Central Nervous System Injury: A Review of the State of Current Clinical Trials;190
12.1;9.1 Ischemic Stroke;191
12.2;9.2 Traumatic Brain Injury;195
12.3;9.3 Spinal Cord Injury;196
12.3.1;9.3.1 Human Trials Using Autologous Bone Marrow Mononuclear Cells Delivered by Intravenous or Intra-arterial Infusion;196
12.3.2;9.3.2 Human Trials Using Autologous Bone Marrow Mononuclear Cells Delivered by Lumbar Puncture;197
12.3.3;9.3.3 Human Trials Using Bone Marrow Mononuclear Cells Delivered by Direct Injection or Surgical Implantation into the Injured Spinal Cord;198
12.3.4;9.3.4 Human Trials Using Embryonically Derived Stem Cell Products;198
12.4;9.4 Conclusions;199
12.5;References;200
13;Index;201