Essentials of Stem Cell Biology

3rd Edition - August 31, 2013

Editors: Robert Lanza, Anthony Atala

Hardback ISBN:

9 7 8 - 0 - 1 2 - 4 0 9 5 0 3 - 8

eBook ISBN:

9 7 8 - 0 - 1 2 - 4 1 0 4 2 7 - 3

First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists,… Read more

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First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners, and students embracing the latest advances in stem cells. Representing the combined effort of 7 editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest research information about specific organ systems. From basic biology/mechanisms, early development, ectoderm, mesoderm, endoderm, and methods to the application of stem cells to specific human diseases, regulation and ethics, and patient perspectives, no topic in the field of stem cells is left uncovered.

Cover image
Title page
Table of Contents
Copyright
Foreword
Preface
List of Contributors
Part I: Introduction to Stem Cells
Chapter 1. Why Stem Cell Research? Advances in the Field
1.1 The Origins of Stem Cell Technology
1.2 Organizations that Advocate and Support the Growth of the Stem Cell Sector
1.3 Applications of Stem Cells in Medicine
1.4 Challenges to the Use of Stem Cells
For Further Study
Chapter 2. ‘Stemness’: Definitions, Criteria, and Standards
2.1 What is a Stem Cell?
2.2 Self-Renewal
2.3 Potency
2.4 Clonality
2.5 Definition
2.6 Where do Stem Cells Come from?
2.7 Stem Cells of the Early Embryo
2.8 Ontogeny of Adult Stem Cells
2.9 How are Stem Cells Identified, Isolated, and Characterized?
2.10 Embryonic Stem Cells
2.11 Adult Stem Cells
2.12 Stemness: Progress Toward a Molecular Definition of Stem Cells
Acknowledgments
For Further Study
Chapter 3. Pluripotent Stem Cells from Vertebrate Embryos: Present Perspective and Future Challenges
3.1 Introduction
3.2 Biology of ES and ESL Cells
3.3 Stem Cell Therapy
3.4 Summary
For Further Study
Chapter 4. Embryonic Stem Cells in Perspective
4.1 Embryonic Stem Cells in Perspective
For Further Study
Chapter 5. The Development of Epithelial Stem Cell Concepts
5.1 Introduction
5.2 A Definition of Stem Cells
5.3 Hierarchically Organized Stem Cell Populations
5.4 Skin Stem Cells
5.5 The Intestinal Stem Cell System
5.6 Stem Cell Organization on the Tongue
5.7 Generalized Scheme
5.8 Summary
For Further Study
Part II: Basic Biology and Mechanisms
Chapter 6. Stem Cell Niches
6.1 Stem Cell Niche Hypothesis
6.2 Stem Cell Niches in the Drosophila Germ-Line
6.3 The Germ-Line Stem Cell Niche in the Drosophila Ovary
6.4 Germ-Line Stem Cell Niche in the Drosophila Testis
6.5 Coordinate Control of Germ-Line Stem Cell and Somatic Stem Cell Maintenance and Proliferation
6.6 Structural Components of the Niche
6.7 Stem Cell Niches Within Mammalian Tissues
6.8 Summary
Acknowledgments
For Further Study
Chapter 7. Mechanisms of Stem Cell Self-Renewal
7.1 Self-Renewal of Pluripotent Stem Cells
7.2 Prevention of Differentiation
7.3 Maintenance of Stem Cell Proliferation
7.4 Maintenance of Telomere Length
7.5 X Chromosome Inactivation
7.6 Summary
For Further Study
Chapter 8. Cell Cycle Regulators in Stem Cells
8.1 Introduction
8.2 Cell Cycle Kinetics of Stem Cells In Vivo
8.3 Stem Cell Expansion Ex Vivo
8.4 Mammalian Cell Cycle Regulation and Cyclin-Dependent Kinase Inhibitors
8.5 Roles of Cyclin-Dependent Kinase Inhibitors in Stem Cell Regulation
8.6 Roles of p21 in Stem Cell Regulation
8.7 Roles of p27 in Stem Cell Regulation
8.8 Other Cyclin-Dependent Kinase Inhibitors and the Retinoblastoma Pathway in Stem Cell Regulation
8.9 Relation Between Cyclin-Dependent Kinase Inhibitors and Transforming Growth Factor β-1
8.10 CKIs and Notch
8.11 Summary and Future Directions
Acknowledgments
For Further Study
Chapter 9. How Cells Change Their Phenotype
9.1 Metaplasia and Transdifferentiation
9.2 Examples of Transdifferentiation
9.3 Barrett’s Metaplasia
9.4 Regeneration
9.5 Bone Marrow to Other Cell Types
9.6 Dedifferentiation as a Prerequisite for Transdifferentiation
9.7 How to Change a Cell’s Phenotype Experimentally
9.8 Summary
Acknowledgments
For Further Study
Part III: Tissue and Organ Development
Chapter 10. Differentiation in Early Development
10.1 Preimplantation Development
10.2 Cell Polarization Occurs During Compaction
10.3 Axis Specification During Preimplantation in the Mouse
10.4 Developmental Potency of the Early Mouse Embryo
10.5 Genes Important During Preimplantation Mouse Development
10.6 From Implantation to Gastrulation
10.7 The Mouse Trophectoderm and Primitive Endoderm Cells
10.8 Development of the Mouse Inner Cell Mass to the Epiblast
10.9 The Human Embryo
10.10 Implantation: Maternal Versus Embryonic Factors
10.11 The Role of Extra-Embryonic Tissues in Patterning the Mouse Embryo
For Further Study
Chapter 11. Stem Cells Derived from Amniotic Fluid
11.1 Amniotic Fluid – Function, Origin, and Composition
11.2 Amniotic Fluid Mesenchymal Stem Cells
11.3 Amniotic Fluid Stem Cells
11.4 Conclusions
For Further Study
Chapter 12. Stem and Progenitor Cells Isolated from Cord Blood
12.1 Addressing Delayed Time to Engraftment and Graft Failure With CB
12.2 Cryopreservation of CB Cells
12.3 Induced Pluripotent Stem Cells Generated from CB
12.4 Concluding Comments
For Further Study
Chapter 13. The Nervous System
13.1 Introduction
13.2 Neural Development
13.3 Neural Stem Cells
13.4 Neural Differentiation of Mouse ES Cells
13.5 Neural Differentiation of Human and Nonhuman Primate ES Cells
13.6 Developmental Perspectives
13.7 Therapeutic Perspectives
13.8 Parkinson’s Disease
13.9 Huntington’s Disease
13.10 Stroke
13.11 Demyelination
13.12 Summary
For Further Study
Chapter 14. Sensory Epithelium of the Eye and Ear
14.1 Introduction
14.2 Introduction to Progenitor and Stem Cells in the Retina
14.3 The Optic Vesicle Generates Diverse Cell Types that can Undergo Transdifferentiation
14.4 In Vivo Neurogenesis in the Posthatch Chicken
14.5 Growth of Retinal Neurospheres from the Ciliary Margin of Mammals
14.6 Prospects for Stem Cell Therapy in the Retina
14.7 Development and Regeneration of Tissues Derived from the Inner Ear
14.8 In Vivo Neurogenesis in Postembryonic Animals
14.9 In Vitro Expansion of Otic Progenitors
14.10 Prospects for Therapy
Acknowledgments
For Further Study
Chapter 15. Epithelial Skin Stem Cells
15.1 A Brief Introduction to Mouse Skin Organization
15.2 The Bulge as a Residence of Epithelial Skin Stem Cells
15.3 Models of Epithelial Stem Cell Activation
15.4 Molecular Fingerprint of the Bulge – Putative Stem Cell Markers
15.5 Cell Signaling in Multipotent Epithelial Skin Stem Cells
15.6 Commentary and Future Directions
For Further Study
Chapter 16. Hematopoietic Stem Cells
16.1 Embryonic Stem Cells and Embryonic Hematopoiesis
16.2 Blood Formation in Embryoid Bodies
16.3 Transformation of an EB-Derived HSC by BCR/ABL
16.4 Promoting Hematopoietic Engraftment with STAT5 and HOXB4
16.5 Promoting Blood Formation In Vitro with Embryonic Morphogens
For Further Study
Chapter 17. Peripheral Blood Stem Cells
17.1 Introduction
17.2 Types and Source of Stem Cells in the Peripheral Blood
17.3 Endothelial Progenitor Cells
17.4 Mesenchymal Stem Cells
17.5 Therapeutic Applications of Peripheral Blood Stem Cells
17.6 Conclusions and Future Directions
For Further Study
Chapter 18. Multipotent Adult Progenitor Cells
18.1 Pluripotent Stem Cells – Embryonic Stem Cells
18.2 Postnatal Tissue-Specific Stem Cells – Are Some More than Multipotent?
18.3 Can Pluripotency Be Acquired?
18.4 Isolation of Rodent MAPCs
18.5 Isolation of Human MAPCs
18.6 Recent Developments
Acknowledgments
For Further Study
Chapter 19. Mesenchymal Stem Cells
19.1 The Definition of MSCs
19.2 The Stem Cell Nature of MSCs
19.3 Which Tissues Contain MSCS?
19.4 MSC Isolation Techniques
19.5 Immunomodulatory Effects of MSCS
19.6 Skeletal Tissue Regeneration by MSCS
19.7 Non-Skeletal Tissue Regeneration by MSCS
19.8 Conclusions
Acknowledgments
For Further Study
Chapter 20. Skeletal Muscle Stem Cells
20.1 Introduction
20.2 The Original Muscle Stem Cell: The Satellite Cell
20.3 Functional and Biochemical Heterogeneity Among Muscle Stem Cells
20.4 Unorthodox Origins of Skeletal Muscle
20.5 The Muscle Stem Cell NICHE
20.6 Conclusion
Acknowledgments
For Further Study
Chapter 21. Cell Lineages and Stem Cells in the Embryonic Kidney
21.1 The Anatomy of Kidney Development
21.2 Genes that Control Early Kidney Development
21.3 The Establishment of Additional Cell Lineages
21.4 What Constitutes a Renal Stem Cell?
Acknowledgments
For Further Study
Chapter 22. Adult Liver Stem Cells
22.1 Organization and Functions of Adult Mammalian Liver
22.2 Liver Stem Cells
For Further Study
Chapter 23. Pancreatic Stem Cells
23.1 Introduction
23.2 Definition of Stem Cells and of Progenitor Cells
23.3 Progenitor Cells During Embryonic Development of the Pancreas
23.4 Progenitor Cells in the Adult Pancreas
23.5 Forcing Other Tissues to Adopt a Pancreatic Phenotype
23.6 In Vitro Studies
23.7 Summary
For Further Study
Chapter 24. Stem Cells in the Gastrointestinal Tract
24.1 Introduction
24.2 Gastrointestinal Mucosa Contains Multiple Lineages
24.3 Epithelial Cell Lineages Originate from a Common Precursor Cell
24.4 Single Intestinal Stem Cells Regenerate Whole Crypts Containing all Epithelial Lineages
24.5 Mouse Aggregation Chimeras Show that Intestinal Crypts are Clonal Populations
24.6 Somatic Mutations in Stem Cells Reveal Stem Cell Hierarchy and Clonal Succession
24.7 Human Intestinal Crypts Contain Multiple Epithelial Cell Lineages Derived from a Single Stem Cell
24.8 Bone Marrow Stem Cells Contribute to Gut Repopulation After Damage
24.9 Gastrointestinal Stem Cells Occupy a Niche Maintained by ISEMFs in the Lamina Propria
24.10 Multiple Molecules Regulate Gastrointestinal Development, Proliferation, and Differentiation
24.11 Wnt/β-Catenin Signaling Pathway Controls Intestinal Stem Cell Function
24.12 Transcription Factors Define Regional Gut Specification and Intestinal Stem Cell Fate
24.13 Gastrointestinal Neoplasms Originate in Stem Cell Populations
24.14 Summary
For Further Study
Part IV: Methods
Chapter 25. Induced Pluripotent Stem Cells
25.1 Generation of iPS Cells
25.2 Molecular Mechanisms in iPS Cell Induction
25.3 Recapitulation of Disease Ontology and Drug Screening
25.4 iPS Cell Banking
25.5 Safety Concerns for Medical Application
25.6 Medical Application
25.7 Direct Fate Switch
25.8 Conclusion
For Further Study
Chapter 26. Embryonic Stem Cells: Derivation and Properties
26.1 Derivation of Embryonic Stem Cells
26.2 Culture of Embryonic Stem Cells
26.3 Developmental Potential of Embryonic Stem Cells
26.4 Conclusion
For Further Study
Chapter 27. Isolation and Maintenance of Murine Embryonic Stem Cells
27.1 Introduction
27.2 Maintenance of Embryonic Stem Cells
27.3 Media
27.4 Sera
27.5 Colony-Forming Assay for Testing Culture Conditions
27.6 Embryonic Stem Cell Passage Culture
27.7 Isolation of New Embryonic STEM Cell Lines
27.8 Method for Deriving Embryonic Stem Cells
27.9 Summary
For Further Study
Chapter 28. Approaches for Derivation and Maintenance of Human Embryonic Stem Cells: Detailed Procedures and Alternatives
28.1 Introduction
28.2 Setting Up the Lab
28.3 Preparing and Screening Reagents
28.4 Mechanical Passaging of hES Cell Colonies
28.5 Derivation of hES Cells
28.6 Maintenance of Established hES Cell Cultures
28.7 Freezing hES Cells
28.8 Thawing hES Cells
28.9 hES Cell Quality Control
For Further Study
Chapter 29. Derivation and Differentiation of Human Embryonic Germ Cells
29.1 Introduction
29.2 Human Embryonic Germ Cell Derivation
29.3 Embryoid Body-Derived Cells
For Further Study
Chapter 30. Genomic Reprogramming
30.1 Introduction
30.2 Genomic Reprogramming in Germ Cells
30.3 Reprogramming Somatic Nuclei
30.4 Conclusions
For Further Study
Part V: Applications
Chapter 31. Neural Stem Cells – Therapeutic Applications in Neurodegenerative Diseases
31.1 Introduction
31.2 Definition of Neural Stem Cells
31.3 Therapeutic Potential of Neural Stem Cells
31.4 Gene Therapy Using Neural Stem Cells
31.5 Cell Replacement Using Neural Stem Cells
31.6 ‘Global’ Cell Replacement Using Neural Stem Cells
31.7 Neural Stem Cells Display an Inherent Mechanism for Rescuing Dysfunctional Neurons
31.8 Neural Stem Cells as the Glue That Holds Multiple Therapies Together
31.9 Summary
For Further Study
Chapter 32. Adult Progenitor Cells as a Potential Treatment for Diabetes
32.1 Importance of β-Cell Replacement Therapy for Diabetes and the Shortage of Insulin-Producing Cells
32.2 Potential of Adult Stem-Progenitor Cells as a Source of Insulin-Producing Cells
32.3 Defining β-Cells, Stem Cells, and Progenitor Cells
32.4 New β-Cells are Formed Throughout Adult Life
32.5 What is the Cellular Origin of Adult Islet Neogenesis?
32.6 Transdifferentiation of Nonislet Cells to Islet Cells
32.7 Pancreatic Acinar Cell Transdifferentiation
32.8 Bone Marrow Cells as a Source of Insulin-Producing Cells
32.9 Liver as a Source of Insulin-Producing Cells
32.10 Engineering Other Non-β-Cells to Produce Insulin
32.11 Attempts to Deliver Insulin Through Constitutive Rather Than Regulated Secretion
32.12 Summary
For Further Study
Chapter 33. Burns and Skin Ulcers
33.1 Introduction
33.2 Burns and Skin Ulcers – The Problem
33.3 Epidermal Stem Cells
33.4 Stem Cells in Burns and Skin Ulcers – Current Use
33.5 Recent and Future Developments
Acknowledgments
For Further Study
Chapter 34. Stem Cells for the Treatment of Muscular Dystrophy
34.1 Introduction
34.2 Myoblast Transplantation – Past Failure and New Hope
34.3 Unconventional Myogenic Progenitors
34.4 Pluripotent Stem Cells for Future Cell-Based Therapies
34.5 Future Perspectives
Acknowledgments
For Further Study
Chapter 35. Cell Therapy for Liver Disease: From Hepatocytes to Stem Cells
35.1 Introduction
35.2 Background Studies
35.3 Integration of Hepatocytes Following Transplantation
35.4 Clinical Hepatocyte Transplantation
35.5 Hepatocyte Bridge
35.6 Hepatocyte Transplantation in Acute Liver Failure
35.7 Hepatocyte Transplantation for Metabolic Liver Disease
35.8 Hepatocyte Transplantation – Novel Uses, Challenges, and Future Directions
35.9 Conclusion
For Further Study
Chapter 36. Orthopedic Applications of Stem Cells
36.1 Introduction
36.2 Bone
36.3 Cartilage
36.4 Meniscus
36.5 Ligaments and Tendons
36.6 Spine
36.7 Summary
For Further Study
Chapter 37. Embryonic Stem Cells in Tissue Engineering
37.1 Introduction
37.2 Tissue Engineering Principles and Perspectives
37.3 Limitations and Hurdles of Using ES Cells in Tissue Engineering
37.4 Summary
For Further Study
Part VI: Regulation and Ethics
Chapter 38. Ethical Considerations
38.1 Introduction
38.2 Is it Morally Permissible to Destroy a Human Embryo?
38.3 Should we Postpone hES Cell Research?
38.4 Can We Benefit from Others’ Destruction of Embryos?
38.5 Can We Create an Embryo to Destroy it?
38.6 Should We Clone Human Embryos?
38.7 What Ethical Guidelines Should Govern hES Cell and Therapeutic Cloning Research?
38.8 Summary
For Further Study
Chapter 39. Overview of the FDA Regulatory Process
39.1 Introduction and Chapter Overview
39.2 Brief Legislative History of FDA
39.3 Laws, Regulations, and Guidance
39.4 FDA Organization and Jurisdictional Issues
39.5 Approval Mechanisms and Clinical Studies
39.6 Meetings with Industry, Professional Groups, and Sponsors
39.7 Regulations and Guidance of Special Interest for Regenerative Medicine
39.8 FDA’s Standards Development Program
39.9 Advisory Committee Meetings
39.10 FDA Research and Critical Path Science
39.11 Other Communication Efforts
39.12 Conclusion
For Further Study
Chapter 40. It’s Not about Curiosity, It’s about Cures: Stem Cell Research – People Help Drive Progress
40.1 Choosing Life
40.2 Size of the Promise
40.3 Personal Promises Fuel Progress
40.4 Hope Versus Hype
40.5 Giving Life
40.6 People Drive Progress
40.7 Better Health for All
Glossary
Index

Robert Lanza

Robert Lanza is an American scientist and author whose research spans the range of natural science, from biology to theoretical physics. TIME magazine recognized him as one of the “100 Most Influential People in the World,” and Prospect magazine named him one of the Top 50 “World Thinkers.” He has hundreds of scientific publications and over 30 books, including definitive references in the fields of stem cells, tissue engineering, and regenerative medicine. He’s a former Fulbright Scholar and studied with polio-pioneer Jonas Salk and Nobel laureates Gerald Edelman (known for his work on the biological basis of consciousness) and Rodney Porter. He also worked closely (and co-authored papers in Science on self-awareness and symbolic communication) with noted Harvard psychologist BF Skinner. Dr. Lanza was part of the team that cloned the world’s first human embryo, the first endangered species, and published the first-ever reports of pluripotent stem cell use in humans.

Affiliations and expertise

Astellas Institute for Regenerative Medicine, Westborough, MA, USA

Anthony Atala

Anthony Atala, MD, is the G. Link Professor and Director of the Wake Forest Institute for Regenerative Medicine, and the W. Boyce Professor and Chair of Urology. Dr. Atala is a practicing surgeon and a researcher in the area of regenerative medicine. Fifteen applications of technologies developed in Dr. Atala's laboratory have been used clinically. He is Editor of 25 books and 3 journals. Dr. Atala has published over 800 journal articles and has received over 250 national and international patents. Dr. Atala was elected to the Institute of Medicine of the National Academies of Sciences, to the National Academy of Inventors as a Charter Fellow, and to the American Institute for Medical and Biological Engineering. Dr. Atala has led or served several national professional and government committees, including the National Institutes of Health working group on Cells and Developmental Biology, the National Institutes of Health Bioengineering Consortium, and the National Cancer Institute’s Advisory Board. He is a founding member of the Tissue Engineering Society, Regenerative Medicine Foundation, Regenerative Medicine Manufacturing Innovation Consortium, Regenerative Medicine Development Organization, and Regenerative Medicine Manufacturing Society.

Affiliations and expertise

Professor, Wake Forest Institute for Regenerative Medicine