Perspectives of Stem Cells - From tools for studying mechanisms of neuronal differentiation towards therapy

Preface

Editor Preface

Contributors

1 Neural Induction

1.1 Introduction

1.2 Neural Induction in the Xenopus Embryo The Early Experiments

1.3 Neural Default Model

1.4 BMP and the Neural Inducers

1.5 Challenges to the Neural Default Model

1.6 Neural Induction and the Avian Node

1.7 Epiblast The Responsive Tissue

1.8 Inhibition of BMP in the Avian Context

1.9 FGF Signaling and Neural Induction

References

2 Neurogenesis: A Change of Paradigms

2.1 Historical Overview

2.2 Neurogenesis and Neurogenic Regions

2.3 Cell Death and Neurogenesis

2.4 Neurogenesis and Inflammation

2.5 Stem Cell Therapies for CNS Disorders

2.6 Concluding Remarks

References

3 Neurogenesis in the Olfactory Epithelium

3.1 Organization of the Mammalian Olfactory System

3.2 The Olfactory Epithelium

3.3 Neurogenesis in the Olfactory Epithelium

3.4 The Olfactory Ensheating Cells

References

4 Cell Diversification During Neural Crest Ontogeny: The Neural Crest Stem Cells

4.1 Introduction

4.2 Formation of the Neural Crest, a Structure Between CNS and Epidermis in Vertebrate Embryos

4.3 Identification of Neural Crest Progenitors and Stem Cells by In Vitro Single Cell Cultures

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

4.5.1 In Vivo Studies

4.5.2 In Vitro Studies

4.6 Plasticity and Dedifferentiation Ability of Neural Crest-Derived Differentiated Cells

4.7 Concluding Remarks

References

5 Intermediate Filament Expression in Mouse Embryonic Stem Cells and Early Embryos

5.1 Intermediate Filaments

5.2 Intermediate Filament Protein Synthesis in Mouse Oocytes and Preimplantation Murine Embryos

5.3 Epithelial Differentiation and Intermediate-Sized Filaments in Early Postimplantation Embryos

5.4 Intermediate Filaments in Primary Mesenchymal Cells in Mouse Embryo

5.5 Expression of Nestin and Synemin During Early Embryogenesis and Differentiation

5.5.1 Nestin and Synemin Genes

5.5.2 Nestin Expression

5.5.3 Synemin Expression

5.6 Expression of Nestin and Synemin in Tumoral Cells of the CNS

5.6.1 Glial Tumors

5.6.2 Nestin in Glioma

5.6.3 Synemin Expression in Glioma

5.6.4 And Now

References

6 Aneuploidy in Embryonic Stem Cells

6.1 Introduction

6.2 A Brief History of Aneuploidy

6.3 Cell Cycle Checkpoints Maintain Genome Integrity

6.4 Increased Levels of Aneuploidy Indicates Reduced Checkpoint Fidelity in Stem/Progenitor Cells

6.5 DNA Damage Signaling and Aneuploidy

6.6 Does Aneuploidy in Stem and/or Progenitor Cells Have Consequences for Development and Disease?

6.7 Aneuploidy and Cancer Stem Cells

6.8 Telomeres and Telomerase Under Genomic Stability Control

6.9 Aneuploidy and Cell-Based Therapy

6.9.1 Mechanical Versus Enzymatic Methods

6.9.2 Risks and Benefits of Aneuploidy to Cell-Based Therapies

References

7 Retrotransposition and Neuronal Diversity

7.1 Introduction

7.2 Silencing and Activation of L1 Retrotransposons

7.3 L1 Targets in Neuronal Progenitor Cells

7.4 Environmental Regulation of L1 Activity in the Brain

7.5 L1 Activity and Disease

7.6 Evolutionary Consequences of L1 Impact in Neuronal Genomes

References

8 Directing Differentiation of Embryonic Stem Cells into Distinct Neuronal Subtypes

8.1 Introduction

8.2 Identifying the Desired ESC-Derived Cell Type for Transplantation

8.3 Generating Neural Progenitors: Back to the Embryo

8.4 Midbrain Dopaminergic Neurons

8.5 GABAergic Interneurons

8.6 Spinal Cord Motor Neurons

8.7 Serotonergic Neurons

8.8 Basal Forebrain Cholinergic Neurons

8.9 Conclusions

References

9 Neurotransmitters as Main Players in the Neural Differentiation and Fate Determination Game

9.1 Introduction

9.2 An Overview of Neurogenesis

9.3 Models of Neuronal Differentiation

9.3.1 Mesenchymal Stem Cells (MSC)

9.3.2 Neural Stem Cells (NSC)

9.3.3 Embryonic Stem (ES) and Embryonal Carcinoma (EC) Cells

9.4 Participation of Neurotransmitters in Neural Differentiation

9.4.1-Aminobutyric Acid (GABA)

9.4.2 Acetylcholine

9.4.3 Glutamate

9.4.4 Purines

9.5 Calcium Signaling and Neuronal Differentiation

9.6 Conclusions

References

10 Rhythmic Expression of Notch Signaling in Neural Progenitor Cells

10.1 Introduction

10.2 Activator-Type bHLH Genes

10.3 Repressor-Type bHLH Genes

10.4 Notch Signaling

10.5 Dynamic Expression in Neural Progenitor Cells

10.6 Oscillatory Versus Persistent Hes1 Expression

10.7 Conclusions

References

11 Neuron-Astroglial Interactions in Cell Fate Commitment in the Central Nervous System

11.1 Introduction. Astroglia: Old Cells, New Concepts

11.2 Astroglial Cells and Neurogenesis

11.2.1 Radial Glia Cells as Progenitor Cells

11.2.2 Potential Roles of Astrocytes in Neurogenic Niches

11.3 Role of Neuron-Glia Interactions in Astrocyte Generation and Maturation

11.3.1 Neuron-Radial Glia Interactions: Implications for Radial Glia Maintenance and Astrocyte Generation

11.3.2 Role of Neuronal-Derived Molecules in Astrocyte Differentiation: Crosstalk Between Growth Factors and Neurotransmitters

11.4 Neuron-Astrocyte Interactions: Implications for Neuronal Differentiation and Synaptogenesis

11.4.1 Neuron-Astrocyte Interactions and Neuronal Differentiation

11.4.2 Role for Glia in Synaptogenesis

11.5 Concluding Remarks

References

12 The Origin of Microglia and the Development of the Brain

12.1 Microglia: Origin and Development

12.1.1 Origin of Microglia

12.1.2 Invasion of the CNS by Microglial Precursors During Development

12.1.3 Expansion of Microglial Population within CNS

12.1.3.1 Proliferation

12.1.3.2 Migration

12.1.3.3 Differentiation

12.1.4 Microglial Development and Thyroid Hormones

12.1.5 Adult CNS: Ramified Microglia

12.2 Microglia and Regressive Processes During Brain Development: Phagocytosis and Neurotoxic Factors

12.3 Microglial Secreted Neurotrophic Factors: Role in Neural Development

12.3.1 Microglia and Neural Progenitor Cells

12.4 The Future

References

13 Tissue Biology of Proliferation and Cell Death Among Retinal Progenitor Cells

13.1 Introduction

13.1.1 Retinal Progenitor Cells

13.1.2 Cell Proliferation in the Retina: On-the-fly Restriction of Phenotype

13.1.3 Retinal Tissue and Microenvironment Around Progenitor Cells

13.2 The Cell Cycle Among Retinal Progenitor Cells

13.2.1 Morphology of Retinal Progenitor Cells

13.2.2 Interkinetic Nuclear Migration and the Cell Cycle in the Developing Retina

13.2.3 The Cell Cycle Machinery in Retinal Progenitor Cells

13.2.4 Checkpoint Control of the Cell Cycle

13.3 Control of Retinal Progenitor Cell Proliferation by Growth Factors and Cytokines

13.3.1 Growth Factors

13.3.2 Interleukins

13.3.3 Neurotrophins

13.3.4 Hedgehog, Notch and Wnt

13.3.5 Platelet Activating Factor

13.4 Control of the Retinal Cell Cycle by Neurotransmitters and Neuromodulators

13.4.1 Classical Neurotransmitters

13.4.1.1 Acetylcholine

13.4.1.2 Glutamate

13.4.1.3 GABA and Glycine

13.4.1.4 Adrenergics

13.4.1.5 Dopamine

13.4.1.6 Serotonin

13.4.1.7 ATP

13.4.1.8 Adenosine

13.4.2 Neuropeptides

13.5 Signal Transduction in the Extrinsic Control of the Retinal Cell Cycle

13.6 Death and Survival of Retinal Progenitor Cells

13.6.1 Mechanisms of Cell Death

13.6.1.1 Apoptosis

13.6.1.2 Autophagy

13.6.1.3 Necrosis

13.6.2 Sensitivity to Cell Death Within the Retinal Cell Cycle

13.6.3 Molecular Mechanisms of Cell Death Among Retinal Progenitor Cells

13.7 Conclusion and Future Directions

References

14 Potential Application of Very Small Embryonic Like (VSEL) Stem Cells in Neural Regeneration

14.1 Introduction

14.2 Identification of Very Small Embryonic Like Stem Cells (VSEL) in Adult Murine Bone Marrow

14.3 Identification of VSEL in Adult Murine Organs Including Adult Brain

14.4 Bone-Marrow-Derived VSEL as Population of Circulating Pluripotent Stem Cells

14.5 Biological Properties of VSEL

14.6 Cells that Express VSEL Markers are Mobilized into PB in Patients After Stroke

14.7 Conclusions

References

15 Embryonic Stem Cell Transplantation for the Treatment of Parkinson0s Disease

15.1 Introduction

15.2 Rationale for Using Transplantation as a Treatment for Parkinsons Disease

15.3 In Vitro Differentiation of Embryonic Stem Cells

15.4 Transplantation in a Parkinsons Disease Model

15.5 Safety Issues for Clinical Application

15.6 Another Donor Candidate: Induced Pluripotent Stem Cell (iPS cell)

References

16 Functional Multipotency of Neural Stem Cells and Its Therapeutic Implications

16.1 Background

16.2 The Neural Stem Cell

16.2.1 Biological Definition

16.2.2 Issues of Cell Identification: Cross-Differentiation and Cell Fusion

16.3 Analysis of Neurogenesis and Neural Stem Cell Fate

16.3.1 In Vivo

16.3.2 In Vitro

16.3.2.1 Epigenetic

16.3.2.2 Genetic

16.4 Clinically Oriented Investigations

16.4.1 Spinal Cord Injury

16.4.2 Neurodegenerative Diseases

16.4.3 Stroke

16.5 Conclusion

References

17 Dual Roles of Mesenchymal Stem Cells in Spinal Cord Injury: Cell Replacement Therapy and as a Model System to Understand Axonal Repair

17.1 Mesenchymal Stem Cells (MSC)

17.2 Biology of Spinal Cord Injury

17.3 Current Interventions for Spinal Cord Injury

17.4 Cytokines and Soluble Factors

17.4.1 Tumor Necrosis Factor Alpha (TNF-)

17.4.2 Leukemia Inhibitory Factor (LIF)

17.4.3 Interlekin-6 (IL-6)

17.4.4 Interleukin-1 (IL-1)

17.4.5 Transforming Growth Factor1 (TGF-1)

17.5 Prospects for Axonal Regeneration in the CNS

17.6 Stem Cell Therapy for Spinal Cord Injury

17.7 Transdifferentiation of Mesenchymal Stem Cells to Neurons

17.8 Other Neurodegenerative Disorders

17.9 Limitations to Stem Cell Therapeutics

17.10 An Interdisciplinary Approach

17.11 Experimental Models for SCI

17.12 On the Frontier of Stem Cell Therapy for Neural Dysfunction

References

Index