Perspectives of Stem Cells (eBook)

Preface 5
Editor Preface 7
Contributors 11
1 Neural Induction 16
1.1 Introduction 16
1.2 Neural Induction in the Xenopus Embryo The Early Experiments 17
1.3 Neural Default Model 7
1.4 BMP and the Neural Inducers 19
1.5 Challenges to the Neural Default Model 19
1.6 Neural Induction and the Avian Node 19
1.7 Epiblast The Responsive Tissue 20
1.8 Inhibition of BMP in the Avian Context 21
1.9 FGF Signaling and Neural Induction 22
References 24
2 Neurogenesis: A Change of Paradigms 26
2.1 Historical Overview 27
2.2 Neurogenesis and Neurogenic Regions 11
2.3 Cell Death and Neurogenesis 32
2.4 Neurogenesis and Inflammation 35
2.5 Stem Cell Therapies for CNS Disorders 38
2.6 Concluding Remarks 40
References 41
3 Neurogenesis in the Olfactory Epithelium 49
3.1 Organization of the Mammalian Olfactory System 49
3.2 The Olfactory Epithelium 50
3.3 Neurogenesis in the Olfactory Epithelium 52
3.4 The Olfactory Ensheating Cells 55
References 56
4 Cell Diversification During Neural Crest Ontogeny: The Neural Crest Stem Cells 60
4.1 Introduction 60
4.2 Formation of the Neural Crest, a Structure Between CNS and Epidermis in Vertebrate Embryos 62
4.3 Identification of Neural Crest Progenitors and Stem Cells by In Vitro Single Cell Cultures 62
4.4 Pluripotent Neural Crest Stem Cells in Tissues and Organs Developmental Remnant and Potential Source of Stem Cells for Regenerative Medicine
4.5 In Vivo and In Vitro Demonstration of the Influence of Environmental Cues on the Differentiation of Neural Crest Derivatives 66
4.5.1 In Vivo Studies 66
4.5.2 In Vitro Studies 66
4.6 Plasticity and Dedifferentiation Ability of Neural Crest-Derived Differentiated Cells 67
4.7 Concluding Remarks 68
References 68
5 Intermediate Filament Expression in Mouse Embryonic Stem Cells and Early Embryos 72
5.1 Intermediate Filaments 72
5.2 Intermediate Filament Protein Synthesis in Mouse Oocytes and Preimplantation Murine Embryos 73
5.3 Epithelial Differentiation and Intermediate-Sized Filaments in Early Postimplantation Embryos 74
5.4 Intermediate Filaments in Primary Mesenchymal Cells in Mouse Embryo 75
5.5 Expression of Nestin and Synemin During Early Embryogenesis and Differentiation 75
5.5.1 Nestin and Synemin Genes 75
5.5.2 Nestin Expression 76
5.5.3 Synemin Expression 77
5.6 Expression of Nestin and Synemin in Tumoral Cells of the CNS 80
5.6.1 Glial Tumors 80
5.6.2 Nestin in Glioma 81
5.6.3 Synemin Expression in Glioma 81
5.6.4 And Now 81
References 82
6 Aneuploidy in Embryonic Stem Cells 86
6.1 Introduction 87
6.2 A Brief History of Aneuploidy 87
6.3 Cell Cycle Checkpoints Maintain Genome Integrity 87
6.4 Increased Levels of Aneuploidy Indicates Reduced Checkpoint Fidelity in Stem/Progenitor Cells 89
6.5 DNA Damage Signaling and Aneuploidy 90
6.6 Does Aneuploidy in Stem and/or Progenitor Cells Have Consequences for Development and Disease? 91
6.7 Aneuploidy and Cancer Stem Cells 93
6.8 Telomeres and Telomerase Under Genomic Stability Control 93
6.9 Aneuploidy and Cell-Based Therapy 94
6.9.1 Mechanical Versus Enzymatic Methods 94
6.9.2 Risks and Benefits of Aneuploidy to Cell-Based Therapies 95
References 96
7 Retrotransposition and Neuronal Diversity 100
7.1 Introduction 100
7.2 Silencing and Activation of L1 Retrotransposons 102
7.3 L1 Targets in Neuronal Progenitor Cells 104
7.4 Environmental Regulation of L1 Activity in the Brain 105
7.5 L1 Activity and Disease 106
7.6 Evolutionary Consequences of L1 Impact in Neuronal Genomes 107
References 108
8 Directing Differentiation of Embryonic Stem Cells into Distinct Neuronal Subtypes 110
8.1 Introduction 111
8.2 Identifying the Desired ESC-Derived Cell Type for Transplantation 111
8.3 Generating Neural Progenitors: Back to the Embryo 113
8.4 Midbrain Dopaminergic Neurons 115
8.5 GABAergic Interneurons 117
8.6 Spinal Cord Motor Neurons 119
8.7 Serotonergic Neurons 121
8.8 Basal Forebrain Cholinergic Neurons 122
8.9 Conclusions 123
References 123
9 Neurotransmitters as Main Players in the Neural Differentiation and Fate Determination Game 128
9.1 Introduction 129
9.2 An Overview of Neurogenesis 129
9.3 Models of Neuronal Differentiation 131
9.3.1 Mesenchymal Stem Cells (MSC) 131
9.3.2 Neural Stem Cells (NSC) 132
9.3.3 Embryonic Stem (ES) and Embryonal Carcinoma (EC) Cells 132
9.4 Participation of Neurotransmitters in Neural Differentiation 133
9.4.1-Aminobutyric Acid (GABA) 133
9.4.2 Acetylcholine 134
9.4.3 Glutamate 135
9.4.4 Purines 137
9.5 Calcium Signaling and Neuronal Differentiation 138
9.6 Conclusions 141
References 141
10 Rhythmic Expression of Notch Signaling in Neural Progenitor Cells 148
10.1 Introduction 148
10.2 Activator-Type bHLH Genes 149
10.3 Repressor-Type bHLH Genes 150
10.4 Notch Signaling 151
10.5 Dynamic Expression in Neural Progenitor Cells 152
10.6 Oscillatory Versus Persistent Hes1 Expression 153
10.7 Conclusions 154
References 155
11 Neuron-Astroglial Interactions in Cell Fate Commitment in the Central Nervous System 157
11.1 Introduction. Astroglia: Old Cells, New Concepts 158
11.2 Astroglial Cells and Neurogenesis 159
11.2.1 Radial Glia Cells as Progenitor Cells 159
11.2.2 Potential Roles of Astrocytes in Neurogenic Niches 161
11.3 Role of Neuron-Glia Interactions in Astrocyte Generation and Maturation 164
11.3.1 Neuron-Radial Glia Interactions: Implications for Radial Glia Maintenance and Astrocyte Generation 164
11.3.2 Role of Neuronal-Derived Molecules in Astrocyte Differentiation: Crosstalk Between Growth Factors and Neurotransmitters 168
11.4 Neuron-Astrocyte Interactions: Implications for Neuronal Differentiation and Synaptogenesis 170
11.4.1 Neuron-Astrocyte Interactions and Neuronal Differentiation 171
11.4.2 Role for Glia in Synaptogenesis 173
11.5 Concluding Remarks 175
References 176
12 The Origin of Microglia and the Development of the Brain 183
12.1 Microglia: Origin and Development 184
12.1.1 Origin of Microglia 185
12.1.2 Invasion of the CNS by Microglial Precursors During Development 186
12.1.3 Expansion of Microglial Population within CNS 187
12.1.3.1 Proliferation 187
12.1.3.2 Migration 188
12.1.3.3 Differentiation 188
12.1.4 Microglial Development and Thyroid Hormones 189
12.1.5 Adult CNS: Ramified Microglia 190
12.2 Microglia and Regressive Processes During Brain Development: Phagocytosis and Neurotoxic Factors 191
12.3 Microglial Secreted Neurotrophic Factors: Role in Neural Development 193
12.3.1 Microglia and Neural Progenitor Cells 194
12.4 The Future 195
References 196
13 Tissue Biology of Proliferation and Cell Death Among Retinal Progenitor Cells 202
13.1 Introduction 203
13.1.1 Retinal Progenitor Cells 204
13.1.2 Cell Proliferation in the Retina: On-the-fly Restriction of Phenotype 205
13.1.3 Retinal Tissue and Microenvironment Around Progenitor Cells 205
13.2 The Cell Cycle Among Retinal Progenitor Cells 206
13.2.1 Morphology of Retinal Progenitor Cells 206
13.2.2 Interkinetic Nuclear Migration and the Cell Cycle in the Developing Retina 207
13.2.3 The Cell Cycle Machinery in Retinal Progenitor Cells 208
13.2.4 Checkpoint Control of the Cell Cycle 209
13.3 Control of Retinal Progenitor Cell Proliferation by Growth Factors and Cytokines 210
13.3.1 Growth Factors 210
13.3.2 Interleukins 211
13.3.3 Neurotrophins 211
13.3.4 Hedgehog, Notch and Wnt 212
13.3.5 Platelet Activating Factor 213
13.4 Control of the Retinal Cell Cycle by Neurotransmitters and Neuromodulators 214
13.4.1 Classical Neurotransmitters 214
13.4.1.1 Acetylcholine 214
13.4.1.2 Glutamate 215
13.4.1.3 GABA and Glycine 217
13.4.1.4 Adrenergics 218
13.4.1.5 Dopamine 218
13.4.1.6 Serotonin 219
13.4.1.7 ATP 219
13.4.1.8 Adenosine 220
13.4.2 Neuropeptides 220
13.5 Signal Transduction in the Extrinsic Control of the Retinal Cell Cycle 221
13.6 Death and Survival of Retinal Progenitor Cells 222
13.6.1 Mechanisms of Cell Death 223
13.6.1.1 Apoptosis 223
13.6.1.2 Autophagy 225
13.6.1.3 Necrosis 226
13.6.2 Sensitivity to Cell Death Within the Retinal Cell Cycle 226
13.6.3 Molecular Mechanisms of Cell Death Among Retinal Progenitor Cells 227
13.7 Conclusion and Future Directions 228
References 229
14 Potential Application of Very Small Embryonic Like (VSEL) Stem Cells in Neural Regeneration 242
14.1 Introduction 243
14.2 Identification of Very Small Embryonic Like Stem Cells (VSEL) in Adult Murine Bone Marrow 243
14.3 Identification of VSEL in Adult Murine Organs Including Adult Brain 245
14.4 Bone-Marrow-Derived VSEL as Population of Circulating Pluripotent Stem Cells 248
14.5 Biological Properties of VSEL 250
14.6 Cells that Express VSEL Markers are Mobilized into PB in Patients After Stroke 250
14.7 Conclusions 252
References 252
15 Embryonic Stem Cell Transplantation for the Treatment of Parkinson0s Disease 255
15.1 Introduction 256
15.2 Rationale for Using Transplantation as a Treatment for Parkinsons Disease 256
15.3 In Vitro Differentiation of Embryonic Stem Cells 257
15.4 Transplantation in a Parkinsons Disease Model 257
15.5 Safety Issues for Clinical Application 258
15.6 Another Donor Candidate: Induced Pluripotent Stem Cell (iPS cell) 261
References 261
16 Functional Multipotency of Neural Stem Cells and Its Therapeutic Implications 265
16.1 Background 266
16.2 The Neural Stem Cell 267
16.2.1 Biological Definition 267
16.2.2 Issues of Cell Identification: Cross-Differentiation and Cell Fusion 267
16.3 Analysis of Neurogenesis and Neural Stem Cell Fate 268
16.3.1 In Vivo 268
16.3.2 In Vitro 269
16.3.2.1 Epigenetic 269
16.3.2.2 Genetic 270
16.4 Clinically Oriented Investigations 271
16.4.1 Spinal Cord Injury 271
16.4.2 Neurodegenerative Diseases 274
16.4.3 Stroke 275
16.5 Conclusion 276
References 276
17 Dual Roles of Mesenchymal Stem Cells in Spinal Cord Injury: Cell Replacement Therapy and as a Model System to Understand Axonal Repair 281
17.1 Mesenchymal Stem Cells (MSC) 282
17.2 Biology of Spinal Cord Injury 282
17.3 Current Interventions for Spinal Cord Injury 283
17.4 Cytokines and Soluble Factors 284
17.4.1 Tumor Necrosis Factor Alpha (TNF-) 284
17.4.2 Leukemia Inhibitory Factor (LIF) 285
17.4.3 Interlekin-6 (IL-6) 285
17.4.4 Interleukin-1 (IL-1) 285
17.4.5 Transforming Growth Factor1 (TGF-1) 285
17.5 Prospects for Axonal Regeneration in the CNS 285
17.6 Stem Cell Therapy for Spinal Cord Injury 286
17.7 Transdifferentiation of Mesenchymal Stem Cells to Neurons 286
17.8 Other Neurodegenerative Disorders 287
17.9 Limitations to Stem Cell Therapeutics 288
17.10 An Interdisciplinary Approach 289
17.11 Experimental Models for SCI 290
17.12 On the Frontier of Stem Cell Therapy for Neural Dysfunction 290
References 291
Index 295