Ulrich Perspectives of Stem Cells

From tools for studying mechanisms of neuronal differentiation towards therapy
1. Auflage 2010
ISBN: 978-90-481-3375-8
Verlag: Springer Netherlands
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 290 Seiten

Stem cells are fascinating cell types. They can replicate themselves forever while retaining the potential to generate progeny with speci?c functions. Because of these special properties, stem cells have been subjects of intensive investigation, from understanding basic mechanisms underlying tissue generation, to modeling human diseases, to application for cell replacement therapy. Stem cells come in different forms. For example, mouse embryonic stem cells can general all cell types in a body, either in a dish or when put back into mouse embryos. On the other hand, neural stem cells in the adult brain generate neurons and glia cells that contribute to the brain’s plasticity. Rapid progress has been made in the stem cell ?eld with discov- ies published in a record speed. A quick Pubmed search has returned 2789 hits for “embryonic stem cells” and 815 hits for “adult neural stem cells/neurogenesis” in the year 2008 alone. It remains a taunting task for all who are interested in stem cells to keep up with rapidly accumulating literatures. The “Perspectives of Stem Cells” by a truly international team of experts provides a timely and invaluable highlight of the stem cell ?eld gearing toward future therapeutic applications in the nervous system. Stem cells with neural potentials have attracted a lot of attention because of their promise for cell replacement therapy, ranging from degenerative neurological dis- ders to spinal cord injuries.

Autoren/Hrsg.

Ulrich, Henning

Inhaltsverzeichnis

1;Preface;5
2;Editor Preface;7
3;Contributors;11
4;1 Neural Induction;16
4.1;1.1 Introduction;16
4.2;1.2 Neural Induction in the Xenopus Embryo The Early Experiments;17
4.3;1.3 Neural Default Model;7
4.4;1.4 BMP and the Neural Inducers;19
4.5;1.5 Challenges to the Neural Default Model;19
4.6;1.6 Neural Induction and the Avian Node;19
4.7;1.7 Epiblast The Responsive Tissue;20
4.8;1.8 Inhibition of BMP in the Avian Context;21
4.9;1.9 FGF Signaling and Neural Induction;22
4.10;References ;24
5;2 Neurogenesis: A Change of Paradigms;26
5.1;2.1 Historical Overview;27
5.2;2.2 Neurogenesis and Neurogenic Regions;11
5.3;2.3 Cell Death and Neurogenesis;32
5.4;2.4 Neurogenesis and Inflammation;35
5.5;2.5 Stem Cell Therapies for CNS Disorders;38
5.6;2.6 Concluding Remarks;40
5.7;References;41
6;3 Neurogenesis in the Olfactory Epithelium;49
6.1;3.1 Organization of the Mammalian Olfactory System;49
6.2;3.2 The Olfactory Epithelium;50
6.3;3.3 Neurogenesis in the Olfactory Epithelium;52
6.4;3.4 The Olfactory Ensheating Cells;55
6.5;References;56
7;4 Cell Diversification During Neural Crest Ontogeny: The Neural Crest Stem Cells;60
7.1;4.1 Introduction;60
7.2;4.2 Formation of the Neural Crest, a Structure Between CNS and Epidermis in Vertebrate Embryos;62
7.3;4.3 Identification of Neural Crest Progenitors and Stem Cells by In Vitro Single Cell Cultures;62
7.4;4.4 Pluripotent Neural Crest Stem Cells in Tissues and Organs; Developmental Remnant and Potential Source of Stem Cells for Regenerative Medicine;64
7.5;4.5 In Vivo and In Vitro Demonstration of the Influence of Environmental Cues on the Differentiation of Neural Crest Derivatives;66
7.5.1;4.5.1 In Vivo Studies;66
7.5.2;4.5.2 In Vitro Studies;66
7.6;4.6 Plasticity and Dedifferentiation Ability of Neural Crest-Derived Differentiated Cells;67
7.7;4.7 Concluding Remarks;68
7.8;References;68
8;5 Intermediate Filament Expression in Mouse Embryonic Stem Cells and Early Embryos;72
8.1;5.1 Intermediate Filaments;72
8.2;5.2 Intermediate Filament Protein Synthesis in Mouse Oocytes and Preimplantation Murine Embryos;73
8.3;5.3 Epithelial Differentiation and Intermediate-Sized Filaments in Early Postimplantation Embryos;74
8.4;5.4 Intermediate Filaments in Primary Mesenchymal Cells in Mouse Embryo;75
8.5;5.5 Expression of Nestin and Synemin During Early Embryogenesis and Differentiation;75
8.5.1;5.5.1 Nestin and Synemin Genes;75
8.5.2;5.5.2 Nestin Expression;76
8.5.3;5.5.3 Synemin Expression;77
8.6;5.6 Expression of Nestin and Synemin in Tumoral Cells of the CNS;80
8.6.1;5.6.1 Glial Tumors;80
8.6.2;5.6.2 Nestin in Glioma;81
8.6.3;5.6.3 Synemin Expression in Glioma;81
8.6.4;5.6.4 And Now;81
8.7; References ;82
9;6 Aneuploidy in Embryonic Stem Cells;86
9.1;6.1 Introduction;87
9.2;6.2 A Brief History of Aneuploidy;87
9.3;6.3 Cell Cycle Checkpoints Maintain Genome Integrity;87
9.4;6.4 Increased Levels of Aneuploidy Indicates Reduced Checkpoint Fidelity in Stem/Progenitor Cells;89
9.5;6.5 DNA Damage Signaling and Aneuploidy;90
9.6;6.6 Does Aneuploidy in Stem and/or Progenitor Cells Have Consequences for Development and Disease?;91
9.7;6.7 Aneuploidy and Cancer Stem Cells;93
9.8;6.8 Telomeres and Telomerase Under Genomic Stability Control;93
9.9;6.9 Aneuploidy and Cell-Based Therapy;94
9.9.1;6.9.1 Mechanical Versus Enzymatic Methods;94
9.9.2;6.9.2 Risks and Benefits of Aneuploidy to Cell-Based Therapies;95
9.10;References;96
10;7 Retrotransposition and Neuronal Diversity;100
10.1;7.1 Introduction;100
10.2;7.2 Silencing and Activation of L1 Retrotransposons;102
10.3;7.3 L1 Targets in Neuronal Progenitor Cells;104
10.4;7.4 Environmental Regulation of L1 Activity in the Brain;105
10.5;7.5 L1 Activity and Disease;106
10.6;7.6 Evolutionary Consequences of L1 Impact in Neuronal Genomes;107
10.7;References;108
11;8 Directing Differentiation of Embryonic Stem Cells into Distinct Neuronal Subtypes;110
11.1;8.1 Introduction;111
11.2;8.2 Identifying the Desired ESC-Derived Cell Type for Transplantation;111
11.3;8.3 Generating Neural Progenitors: Back to the Embryo;113
11.4;8.4 Midbrain Dopaminergic Neurons;115
11.5;8.5 GABAergic Interneurons;117
11.6;8.6 Spinal Cord Motor Neurons;119
11.7;8.7 Serotonergic Neurons;121
11.8;8.8 Basal Forebrain Cholinergic Neurons;122
11.9;8.9 Conclusions;123
11.10;References;123
12;9 Neurotransmitters as Main Players in the Neural Differentiation and Fate Determination Game;128
12.1;9.1 Introduction;129
12.2;9.2 An Overview of Neurogenesis;129
12.3;9.3 Models of Neuronal Differentiation;131
12.3.1;9.3.1 Mesenchymal Stem Cells (MSC);131
12.3.2;9.3.2 Neural Stem Cells (NSC);132
12.3.3;9.3.3 Embryonic Stem (ES) and Embryonal Carcinoma (EC) Cells;132
12.4;9.4 Participation of Neurotransmitters in Neural Differentiation;133
12.4.1;9.4.1-Aminobutyric Acid (GABA);133
12.4.2;9.4.2 Acetylcholine;134
12.4.3;9.4.3 Glutamate;135
12.4.4;9.4.4 Purines;137
12.5;9.5 Calcium Signaling and Neuronal Differentiation;138
12.6;9.6 Conclusions;141
12.7; References ;141
13;10 Rhythmic Expression of Notch Signaling in Neural Progenitor Cells;148
13.1;10.1 Introduction;148
13.2;10.2 Activator-Type bHLH Genes;149
13.3;10.3 Repressor-Type bHLH Genes;150
13.4;10.4 Notch Signaling;151
13.5;10.5 Dynamic Expression in Neural Progenitor Cells;152
13.6;10.6 Oscillatory Versus Persistent Hes1 Expression;153
13.7;10.7 Conclusions;154
13.8;References;155
14;11 Neuron-Astroglial Interactions in Cell Fate Commitment in the Central Nervous System;157
14.1;11.1 Introduction. Astroglia: Old Cells, New Concepts;158
14.2;11.2 Astroglial Cells and Neurogenesis;159
14.2.1;11.2.1 Radial Glia Cells as Progenitor Cells;159
14.2.2;11.2.2 Potential Roles of Astrocytes in Neurogenic Niches;161
14.3;11.3 Role of Neuron-Glia Interactions in Astrocyte Generation and Maturation;164
14.3.1;11.3.1 Neuron-Radial Glia Interactions: Implications for Radial Glia Maintenance and Astrocyte Generation;164
14.3.2;11.3.2 Role of Neuronal-Derived Molecules in Astrocyte Differentiation: Crosstalk Between Growth Factors and Neurotransmitters;168
14.4;11.4 Neuron-Astrocyte Interactions: Implications for Neuronal Differentiation and Synaptogenesis;170
14.4.1;11.4.1 Neuron-Astrocyte Interactions and Neuronal Differentiation;171
14.4.2;11.4.2 Role for Glia in Synaptogenesis;173
14.5;11.5 Concluding Remarks;175
14.6;References;176
15;12 The Origin of Microglia and the Development of the Brain;183
15.1;12.1 Microglia: Origin and Development;184
15.1.1;12.1.1 Origin of Microglia;185
15.1.2;12.1.2 Invasion of the CNS by Microglial Precursors During Development;186
15.1.3;12.1.3 Expansion of Microglial Population within CNS;187
15.1.3.1;12.1.3.1 Proliferation;187
15.1.3.2;12.1.3.2 Migration;188
15.1.3.3;12.1.3.3 Differentiation;188
15.1.4;12.1.4 Microglial Development and Thyroid Hormones;189
15.1.5;12.1.5 Adult CNS: Ramified Microglia;190
15.2;12.2 Microglia and Regressive Processes During Brain Development: Phagocytosis and Neurotoxic Factors;191
15.3;12.3 Microglial Secreted Neurotrophic Factors: Role in Neural Development;193
15.3.1;12.3.1 Microglia and Neural Progenitor Cells;194
15.4;12.4 The Future;195
15.5;References;196
16;13 Tissue Biology of Proliferation and Cell Death Among Retinal Progenitor Cells;202
16.1;13.1 Introduction;203
16.1.1;13.1.1 Retinal Progenitor Cells;204
16.1.2;13.1.2 Cell Proliferation in the Retina: On-the-fly Restriction of Phenotype;205
16.1.3;13.1.3 Retinal Tissue and Microenvironment Around Progenitor Cells;205
16.2;13.2 The Cell Cycle Among Retinal Progenitor Cells;206
16.2.1;13.2.1 Morphology of Retinal Progenitor Cells;206
16.2.2;13.2.2 Interkinetic Nuclear Migration and the Cell Cycle in the Developing Retina;207
16.2.3;13.2.3 The Cell Cycle Machinery in Retinal Progenitor Cells;208
16.2.4;13.2.4 Checkpoint Control of the Cell Cycle;209
16.3;13.3 Control of Retinal Progenitor Cell Proliferation by Growth Factors and Cytokines;210
16.3.1;13.3.1 Growth Factors;210
16.3.2;13.3.2 Interleukins;211
16.3.3;13.3.3 Neurotrophins;211
16.3.4;13.3.4 Hedgehog, Notch and Wnt;212
16.3.5;13.3.5 Platelet Activating Factor;213
16.4;13.4 Control of the Retinal Cell Cycle by Neurotransmitters and Neuromodulators;214
16.4.1;13.4.1 Classical Neurotransmitters;214
16.4.1.1;13.4.1.1 Acetylcholine;214
16.4.1.2;13.4.1.2 Glutamate;215
16.4.1.3;13.4.1.3 GABA and Glycine;217
16.4.1.4;13.4.1.4 Adrenergics;218
16.4.1.5;13.4.1.5 Dopamine;218
16.4.1.6;13.4.1.6 Serotonin;219
16.4.1.7;13.4.1.7 ATP;219
16.4.1.8;13.4.1.8 Adenosine;220
16.4.2;13.4.2 Neuropeptides;220
16.5;13.5 Signal Transduction in the Extrinsic Control of the Retinal Cell Cycle;221
16.6;13.6 Death and Survival of Retinal Progenitor Cells;222
16.6.1;13.6.1 Mechanisms of Cell Death;223
16.6.1.1;13.6.1.1 Apoptosis;223
16.6.1.2;13.6.1.2 Autophagy;225
16.6.1.3;13.6.1.3 Necrosis;226
16.6.2;13.6.2 Sensitivity to Cell Death Within the Retinal Cell Cycle;226
16.6.3;13.6.3 Molecular Mechanisms of Cell Death Among Retinal Progenitor Cells;227
16.7;13.7 Conclusion and Future Directions;228
16.8;References;229
17;14 Potential Application of Very Small Embryonic Like (VSEL) Stem Cells in Neural Regeneration;242
17.1;14.1 Introduction;243
17.2;14.2 Identification of Very Small Embryonic Like Stem Cells (VSEL) in Adult Murine Bone Marrow;243
17.3;14.3 Identification of VSEL in Adult Murine Organs Including Adult Brain;245
17.4;14.4 Bone-Marrow-Derived VSEL as Population of Circulating Pluripotent Stem Cells;248
17.5;14.5 Biological Properties of VSEL;250
17.6;14.6 Cells that Express VSEL Markers are Mobilized into PB in Patients After Stroke;250
17.7;14.7 Conclusions;252
17.8;References;252
18;15 Embryonic Stem Cell Transplantation for the Treatment of Parkinson0s Disease;255
18.1;15.1 Introduction;256
18.2;15.2 Rationale for Using Transplantation as a Treatment for Parkinsons Disease;256
18.3;15.3 In Vitro Differentiation of Embryonic Stem Cells;257
18.4;15.4 Transplantation in a Parkinsons Disease Model;257
18.5;15.5 Safety Issues for Clinical Application;258
18.6;15.6 Another Donor Candidate: Induced Pluripotent Stem Cell (iPS cell);261
18.7; References ;261
19;16 Functional Multipotency of Neural Stem Cells and Its Therapeutic Implications;265
19.1;16.1 Background;266
19.2;16.2 The Neural Stem Cell;267
19.2.1;16.2.1 Biological Definition;267
19.2.2;16.2.2 Issues of Cell Identification: Cross-Differentiation and Cell Fusion;267
19.3;16.3 Analysis of Neurogenesis and Neural Stem Cell Fate;268
19.3.1;16.3.1 In Vivo;268
19.3.2;16.3.2 In Vitro;269
19.3.2.1;16.3.2.1 Epigenetic;269
19.3.2.2;16.3.2.2 Genetic;270
19.4;16.4 Clinically Oriented Investigations;271
19.4.1;16.4.1 Spinal Cord Injury;271
19.4.2;16.4.2 Neurodegenerative Diseases;274
19.4.3;16.4.3 Stroke;275
19.5;16.5 Conclusion;276
19.6;References;276
20;17 Dual Roles of Mesenchymal Stem Cells in Spinal Cord Injury: Cell Replacement Therapy and as a Model System to Understand Axonal Repair;281
20.1;17.1 Mesenchymal Stem Cells (MSC);282
20.2;17.2 Biology of Spinal Cord Injury;282
20.3;17.3 Current Interventions for Spinal Cord Injury;283
20.4;17.4 Cytokines and Soluble Factors;284
20.4.1;17.4.1 Tumor Necrosis Factor Alpha (TNF-);284
20.4.2;17.4.2 Leukemia Inhibitory Factor (LIF);285
20.4.3;17.4.3 Interlekin-6 (IL-6);285
20.4.4;17.4.4 Interleukin-1 (IL-1);285
20.4.5;17.4.5 Transforming Growth Factor1 (TGF-1);285
20.5;17.5 Prospects for Axonal Regeneration in the CNS;285
20.6;17.6 Stem Cell Therapy for Spinal Cord Injury;286
20.7;17.7 Transdifferentiation of Mesenchymal Stem Cells to Neurons;286
20.8;17.8 Other Neurodegenerative Disorders;287
20.9;17.9 Limitations to Stem Cell Therapeutics;288
20.10;17.10 An Interdisciplinary Approach;289
20.11;17.11 Experimental Models for SCI;290
20.12;17.12 On the Frontier of Stem Cell Therapy for Neural Dysfunction;290
20.13;References ;291
21;Index;295