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Beschreibung

This third in the Current Topics in Molecular Cell Biology and Molecular Medicine Series contains a careful selection of new and updated, high-quality articles from the well-known Meyer's Encyclopedia, describing new perspectives in stem cell research. The 26 chapters are divided into four sections: Basic Biology, Stem Cells and Disease, Stem Cell Therapy Approaches, and Laboratory Methods, with the authors chosen from among the leaders in their respective fields.

This volume represents an essential guide for students and researchers seeking an overview of the field.

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Veröffentlichungsjahr: 2013

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Table of Contents

Related Titles

Title Page

Copyright

Preface

Volume 1

Part I: Basic Biology

1: Epigenetic Regulation in Pluripotent Stem Cells*

1 Introduction

2 DNA Methylation

3 Histone Modifications and Histone Variants

4 Higher-Order Structure of Chromatin

5 X-Chromosome Inactivation

6 Regulation of ESC Pluripotency and Differentiation by miRNAs

7 Telomere Function and Genomic Stability in ESCs

8 Imprinting and ESC Stability

9 Epigenetic Interconversion among Mouse ESCs, EpiSCs, and Human ESCs

10 Summary

References

2: Induced Pluripotent Stem Cells

1 Introduction

2 iPSCs

3 Application of iPS Cells

4 Conclusions

Acknowledgments

References

3: Naturally Occurring Adult Pluripotent Stem Cells

1 Introduction

2 What Are Adult Pluripotent Stem Cells?

3 What Are Progenitor Cells?

4 Isolation and Characterization of Pluripotent Stem Cells

5 Differences Between Induced Pluripotent Stem (iPS) Cells and Naturally Occurring Adult Pluripotent Stem Cells

6 Locations of Adult Pluripotent Stem Cells

7 Normal Functions of Adult Pluripotent Stem Cells

8 Obtaining Adult Pluripotent Stem Cells

9 The Use of Adult Pluripotent Stem Cells in Regenerative Medicine

10 Proposed Uses for Adult Pluripotent Stem Cells

Acknowledgments

References

4: Spermatogonial stem cell (SSCs) system

Abbreviations

1 Introduction

2 Understanding Stem Cell Genes

3 The Mammalian Spermatogonial Stem Cell

4 Crucial Signaling Pathways in Regulating the Fate of SS Cells

5 MicroRNAs in the Regulation of Spermatogenesis

6 Isolation, Characterization, and Culture of Mouse and Human Spermatogonia

7 The Significance of SS Cells Outside Their Niche: The Emergence of the Pluripotent Adult Stem Cell

8 Concluding Remarks: Summary of the Significance of SS Cells

Acknowledgments

References

5: Stem Cell Dormancy: Maintaining a Reserved Population

1 Introduction

2 Purpose of Stem Cell Quiescence and Dormancy

3 History

4 Factors Regulating Quiescence

5 Factors Regulating Dormancy

6 Cancer Relevance

References

6: Stem Cells in the Adult Brain: Neurogenesis

1 Brief Historical Significance

2 Identity and Properties of Adult Neural Stem Cells

3 Adult Neurogenesis Niche

4 Regulation of Adult Neural Stem Cells and Neural Progenitor Cells

5 Evolving Concepts of Adult Neural Stem Cells

6 Conclusions

Acknowledgments

References

7: Embryonic Stem Cells

1 Embryonic Development

2 Derivation of ES Cells

3 Basic Properties of ES Cells

4 Similarities and Differences Among ES Cells Derived from Different Species

5 Culturing ES Cells

6 Differentiation of ES Cells and Other Pluripotent Cells

7 Other Stem Cell Populations, ES-Like Cells, Primordial Germ Cell, and Epiblast Cells

8 iPSCs

9 Uses of ES Cells and Other Pluripotent Cells

References

Further Reading

Books and Reviews

Primary Literature

Part I: Laboratory Methods

8: Cardiomyocytes from Human Embryonic Stem Cells

1 Introduction

2 Signaling and Regulation in Heart Development: Molecular Insights into hESC Differentiation

3 Differentiation of hESCs to Cardiomyocytes

4 Characterization of hESC-Derived Cardiomyocytes

5 Scale-Up and Enrichment of hESC-CMs

6 Translational Research in hESC-CMs

7 Conclusions and Future Outlook

Acknowledgements

References

9: Cloned Mice from Adult Stem Cells

1 Introduction

2 The Success Rate of Mammalian Cloning and Differentiation Status of Donor Cells

3 Epigenetic Status of Cloned Animals

4 Application of Somatic Cell Nuclear Transfer Technology

5 Conclusions

References

10: Cloned Mice from Embryonic Stem Cells

1 Introduction

2 Improvements in the Success Rate of Mouse Somatic Cell Cloning

3 Establishment of ES Cells from Somatic Cells via Nuclear Transfer

4 The Value of Mouse Cloning Using an ntES Cell Line

5 Conclusions

References

11: Haploid Embryonic Stem Cells

1 Introduction

2 History and Rationale

3 Approaches to Haploid ES Cell Culture

4 Applications of Haploid ES Cells

5 Concluding Remarks

Acknowledgments

References

Notes added to proof

12: Muscle Stem Cells: Their Discovery, Properties, and In-Vitro Manipulation

1 Seeking the Source of Skeletal Muscle's Vast Ability to Repair

2 Vindicating the Satellite Cell as a Muscle Stem Cell: Verification as the Physiological Muscle Stem Cell

3 Regulating Muscle Stem Cell Self-Renewal in Culture: In Vivo Lessons and In Vitro Implementations

4 Ongoing Optimization of Muscle Stem Cell Self-Renewal in Culture

Acknowledgments

References

13: Nuclear Transfer for Cloning Animals*

1 Introduction and Brief Historical Overview

2 Key Elements and Critical Aspects of NT Technology

3 Applications of NT in Different Species

4 Future Perspectives of NT

Acknowledgments

References

14: Induction of Pluripotent Stem Cells from Umbilical Cord Blood

1 Introduction

2 The iPSC Technology

3 Sources of Human Cells for hiPSC Generation

4 Cord Blood as the Premium Tissue for Reprogramming

5 Reprogramming Human Cord Blood with Integrating Vectors

6 Reprogramming Cord Blood with Non-Integrating Episomal System

7 Epigenetic Memory and Genetic Stability of Blood-Derived iPSCs

8 Concluding Remarks

Acknowledgments

References

15: Development and Renewal of Ventricular Heart Muscle from Intrinsic Progenitor Cells

1 Introduction

2 Perspectives on Stem/Progenitor Cells in the Developing Heart

3 Emergence of Cardiac Progenitors in the Embryo

4 Specification of the Early Cardiogenic Fate

5 Progenitors in the First Heart Field

6 Progenitors in the Second Heart Field

7 Regional Specification of the Developing Heart

8 Epicardial Progenitor Cells

9 Postnatal Cardiomyocyte Turnover

10 Postnatal and Adult Cardiac Stem/Progenitor Cells

11 Cardiac Stem/Progenitor Cells for Postnatal Myocardial Regeneration

12 Conclusion

References

Volume 2

Part III: Stem Cell Therapy

16: Gene Therapy of Genetic Diseases of Blood Cells

1 Genetic Diseases of Blood Cells

2 Allogeneic HSCT as Treatment of Genetic Diseases of Blood Cells

3 Gene Therapy

4 Severe Combined Immune Deficiency (SCID)

5 Wiskott–Aldrich Syndrome

6 Chronic Granulomatous Disease

7 Hemoglobinopathies

8 Lysosomal Storage Diseases and Metabolic Diseases

9 Gene Correction by Homologous Recombination

10 Summary

References

17: Mesenchymal Stem Cells Characteristics, Niches, and Applications for Cell Therapy

1 Introduction

2 MSC Sources and Isolation

3 MSC Characteristics

4 MSCs and Immunomodulation

5 MSC Therapy

6 MSCs and Cancer

7 Concluding Remarks

Acknowledgments

18: Stem Cells and Parkinson's Disease

1 Introduction

2 Neuroregeneration and Cell Therapy

3 Novel Stem Cell Sources for Neural Cell Therapy

4 Neural and Dopaminergic Differentiation of Human Pluripotent Stem Cells

5 Neural Cell Sorting

6 Current Challenges and Outlook

7 Summary and Conclusion

References

19: Stem Cell-Based Approaches to Spinal Cord Injury

1 Introduction

2 Stem Cells: An Overview

3 Endogenous Neural Progenitor Cells

4 Embryonic Stem Cells

5 Stem Cell Growth

6 Predifferentiation of ESC Cells

7 Clinical Trials

8 Clinical Concerns

9 Summary and Conclusion

References

20: Therapeutics against Cancer Stem Cells: Targeting the Root of Cancer

1 Introduction

2 Cancer Stem Cells

3 Stem Cell-Related Signaling Pathways

4 Additional Cancer Stem Cell Targets

5 Cancer Stem Cell Niche

6 CSCs in Drug Discovery

7 Concluding Remarks

References

21: Translating Stem Cells to the Clinic: From Modeling Disease to Cellular Products

1 Introduction

2 The Promises of Pluripotency

3 Lineage Conversion and Plasticity: New Kids for the Future of Regenerative Medicine

4 Multipotent Adult Stem Cells: The Alternative to Pluripotency

5 Gene Editing and Disease Modeling

6 Conclusions

References

Part IV: Stem Cells and Disease

22: Cancer Stem Cells

1 Introduction

2 Identification and Characterization of the CSCs

3 Signaling Pathways and Factors Involved in the Regulation of CSCs

4 CSCs and the Microenvironment

5 Radiation and Chemotherapy Resistance of CSCs

6 Targeting CSCs

7 Conclusions

References

23: Normal and Neoplastic Stem Cells

1 Introduction

2 Characteristics and Functions of Stem cells

3 Neoplastic Stem Cells

4 Implications of Neoplastic Stem Cells for the Treatment of Cancer

5 Conclusions

References

24: Prostate Tissue Stem Cells and Prostate Cancer Progression

1 Introduction

2 Mouse Prostate Stem and Progenitor Cells

3 Human Prostate Stem Cells

4 Molecular Mechanisms Regulating Prostate Cell Fate

5 Outstanding Questions

Acknowledgments

References

25: The Stem Cell Niche and Its Role in Self-Renewal, Aging, and Malignancy

1 The Stem Cell Niche and Its Role in Stem Cell Self-Renewal

2 The Stem Cell Niche and Its Role in Aging

3 The Stem Cell Niche and Its Role in Carcinogenesis

References

26: Stem Cells and Colon Cancer

1 Colorectal Cancer

2 Treatment Option Overview: Strategy of Treatment by Stage

3 Targeting the Differentiation and Survival Signaling in CSCs

Acknowledgments

References

Index

Related Titles

Meyers, R. A. (ed.)

Encyclopedia of Molecular Cell Biology and Molecular Medicine

Online version: www.meyers-emcbmm.com

Freshney, R., Stacey, G.N., Auerbach, J.M.

Culture of Human Stem Cells

2007

ISBN: 978-0-470-05246-4, also available in digital formats

Bhatia, M. (ed.)

Current Protocols in Stem Cell Biology

ISBN: 978-0-470-52831-0, also available in digital formats at CurrentProtocols.com

Perinatal Stem Cells, 2nd Edition

2013

ISBN: 978-1-1182-0944-8, also available in digital formats

Bapat, S.A. (ed.)

Cancer Stem Cells

Identification and Targets

2009

ISBN: 978-0-470-12201-3, also available in digital formats

Stein, G.S., Borowski, M., Luong, M.X., Shi, M.-J., Smith, K.P., Vazquez, P. (eds.)

Human Stem Cell Technology and Biology: A Research Guide and Laboratory Manual

2011

ISBN: 978-0-470-59545-9, also available in digital formats

Ramalingam, M., Jabbari, E., Ramakrishna, S., Khademhosseini, A. (Eds.)

Micro and Nanotechnologies in Engineering Stem Cells and Tissues

2013

ISBN: 978-1-1181-4042-0, also available in digital formats

Uma Lakshmipathy, U., Thyagarajan, B.

Primary and Stem Cells: Gene Transfer Technologies and Applications

2012

ISBN: 978-0-470-61074-9, also available in digital formats

The Editor

Dr. Robert A. Meyers

Editor in Chief

RAMTECH LIMITED

122, Escalle Lane

Larkspur, CA 94939

USA

Cover

Image of human iPSCs in feeder-free culture conditions. For more details see figure 1 in chapter 2 ``Induced Pluripotent Stem Cells'' authored by Kazutoshi Takahashi and Shinya Yamanaka.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty can be created or extended by sales representatives or written sales materials. The Advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

Wiley-Blackwell is an imprint of John Wiley & Sons, formed by the merger of Wiley's global Scientific, Technical, and Medical business with Blackwell Publishing.

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form — by photoprinting, microfilm, or any other means — nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978-3-527-32925-0

ePDF ISBN: 978-3-527-66854-0

ePub ISBN: 978-3-527-66852-6

Mobi ISBN: 978-3-527-66853-3

Preface

Five Nobel Laureates are associated with this book: the Encyclopedia of Molecular Biology and Molecular Medicine Board members, Sir Martin Evans, who won a Nobel in Physiology or Medicine in 2007 for isolating embryonic stem cells and then growing them in culture; as well as David Baltimore, Gunter Blobel, and Phil Sharp; and now contributing author Shinya Yamanaka, whose 2012 Nobel Prize for Physiology or Medicine was awarded for reprogramming mature cells to become pluripotent stem cells. Professor Yamanaka's chapter on Induced Pluripotent Stem Cells, written for our book, forms a central component, tying together all aspects of stem cells biology and applications.

In his chapter, Professor Yamanaka points out the central issues associated with clinical application of stem cells. “Because pluripotent stem cells can theoretically differentiate into all cell types in the body, applications for cell therapy are expected. However, it is unclear when ES and/or iPS cells would be effective for cell therapy. The most common issue preventing the clinical use of ES and iPS cells is the risk of teratoma formation after transplantation. Residual undifferentiated cells in differentiated cell cultures used for a transplant can cause a teratoma, and should be removed before use. Both effective methods for the removal of undifferentiated cell contamination, such as the use of flow cytometry, and more efficient procedures for differentiation are being developed”. Beyond these, there are additional important potential hurdles to clinical applications, including: the need for xeno-free stem cell lines, epigenetic memory and aberrant genetic errors which may be higher for iPS cells as compared with ES cells. All of these factors are covered in detail in our chapters.

The 26 detailed chapters, prepared by leaders in the field, cover the basic biology of stem cells, laboratory methods, stem cells and disease and stem cell therapy approaches and translation to the clinic for treatment of many diseases including Parkinson's disease, spinal cord trauma, diseases of blood cells, and many types of cancer as well as regeneration of cardiac and other muscle tissue. The chapter on “Translating Stem Cells to the Clinic: from modeling disease to cellular products” by Juan Carlos Izpisua Belmonteand his team at the Salk Institute presents the state and future of stem cell clinical applications including 1) “disease in a dish” laboratory substrates providing patient-specific iPS cells which can be employed for disease modeling and drug development; 2) the possibility to generate every desired cell type in vitro for restoration of any injury from lost tissue by cell replacement and gene-editing technologies that efficiently target both and 3) pluripotent cells as well as adult stem cells giving rise to the possibility for gene-correction followed by autologous transplantation which could be employed for the actual cure of monogenic inherited diseases in patients.

Our team hopes that you, the reader, will benefit from our hard work, finding the content useful in your research and educational. We wish to thank our Managing Editor, Sarah Mellor as well as our Executive Editor, Gregor Cicchetti for both their advice and hard work in the course of this project.

Larkspur, California, March 2013

Robert A. Meyers

Editor-in-Chief

RAMTECH LIMITED

Volume 1

Part I

Basic Biology

1

Epigenetic Regulation in Pluripotent Stem Cells*

Lin Liu and Lingyi Chen

Nankai University, The Ministry of Education, Key Laboratory of Bioactive Materials, Laboratory of Stem Cells and Developmental Biology, College of Life Sciences, 94 Weijin Road, Tianjin 300071, China

1 Introduction

2 DNA Methylation

3 Histone Modifications and Histone Variants

4 Higher-Order Structure of Chromatin

5 X-Chromosome Inactivation

6 Regulation of ESC Pluripotency and Differentiation by miRNAs

7 Telomere Function and Genomic Stability in ESCs

8 Imprinting and ESC Stability

9 Epigenetic Interconversion among Mouse ESCs, EpiSCs, and Human ESCs

10 Summary

Keywords

Embryonic stem cells (ESCs)

Pluripotent cells derived and cultured from the inner cell mass of blastocysts or from blastomeres of early embryos. These cells are able to proliferate and self-renew indefinitely, and to maintain undifferentiated states under correct culture conditions, while retaining the potential to differentiate into all types of cell in the body.

Induced pluripotent stem cells (iPSCs)

By ectopic expression of a few transcription factors (e.g., Oct4, Sox2, Klf4, and c-Myc), differentiated cells are reprogrammed and give rise to ESC-like cells. The latter are also pluripotent and able to self-renew; hence, they are termed iPS cells (iPSCs).

Totipotency

Cells sufficient to form an entire organism by themselves. Examples are zygotes and few cells in early-cleavage embryos in mammals.

Pluripotency

The developmental potential of a cell to differentiate into all types of cell in the body. The most stringent test for developmental pluripotency is the generation of offspring completely from ESCs/iPSCs by tetraploid embryo complementation, or by four- to eight-cell embryo injection. A less stringent test is the production of germline-competent chimeras by either diploid blastocyst or four- to eight-cell embryo-injection methods.

Reprogramming

An increase in the developmental potency from a differentiated to an undifferentiated stage; also referred to as dedifferentiation in some instances.

Epigenetics

Changes in gene function that are mitotically and/or mitotically inheritable, and that do not entail a change in DNA sequences. Epigenetic information includes changes in gene expression by DNA methylation, microRNAs, histone modifications, histone variants, nucleosome positioning, and higher-order chromatin structure.

DNA methylation

The addition of methyl groups to DNA, mostly at CpG sites, to convert cytosine to 5-methylcytosine. DNA methylation usually represses gene expression.

Histone

Proteins enriched in positively charged amino acid residuals, found in eukaryotic cell nuclei. These proteins package and order the DNA into structural units called nucleosomes.

Nucleosome

The basic unit of chromatin. In a nucleosome, a DNA fragment of 147bp is wrapped around spools of histone proteins.

Histone modification

Modification in the entire sequence of histones, particularly at the unstructured N-termini (histone tails), including acetylation, methylation, ubiquitylation, phosphorylation, and SUMOylation. Histone acetylation or the inhibition of histone deacetylation is generally linked to transcriptional activation.

Imprinting

The allele-specific expression of a small subset of mammalian genes in a parent-of-origin manner (either the paternal or maternal is monoallelically expressed). The establishment of genomic imprinting is controlled mostly by DNA methylation, and also by histone modifications, noncoding RNAs, and specialized chromatin structures. Aberrant imprinting disrupts fetal development, and is associated with genetic diseases, some cancers, and a number of neurological disorders.

X chromosome inactivation

In each mammalian female cell, one of the two X chromosomes is transcriptionally inactivated to compensate any X-linked gene dosage effect between male (XY) and female (XX).

Telomere

Repeated DNA sequences (TTAGGG)n and associated protein complexes that cap the end of chromosomes to maintain genomic stability. Telomere shortening is associated with cell senescence and organism aging, and also cancer.

Telomerase

An enzyme that specifically adds telomeric repeats de novo during each cell division, and is composed of two major components: a telomerase RNA template component (Terc); and Tert, a reverse transcriptase as a catalytic unit. ESCs acquire high telomerase activity to maintain telomere length.

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