Essentials of Stem Cell Biology,

Edition 4

Editors: Edited by Robert Lanza and Anthony Atala, MD

Publication Date: 01 Jun 2026

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Essentials of Stem Cell Biology, Fourth Edition is designed for the growing community of scientists, researchers, practitioners, and students embracing the latest advancements in stem cells. This comprehensive book, a collaboration of 7 editors and over 200 pioneering scholars and scientists, provides a thorough understanding of adult and embryonic stem cells. It combines fundamental concepts with cutting-edge research in specific organ systems, ensuring a robust foundation for anyone entering the field. Beyond the basics, the book delves into early development and the differentiation of ectoderm, mesoderm, and endoderm.

It covers methods, applications to human diseases, regulation, ethics, and patient perspectives, leaving no stone unturned in the stem cell domain.

Key Features

Contains contributions from Nobel Laureates and leading international investigators
Includes two entirely new chapters devoted exclusively to induced pluripotent stem (iPS) cells
Edited by a world-renowned author and researcher to present a complete story of stem cells in research, in application, and as the subject of political debate
Presented in full color with a glossary, highlighted terms, and bibliographic entries replacing references

About the author

Edited by Robert Lanza, Astellas Institute for Regenerative Medicine, Westborough, MA, USA; Anthony Atala, MD, G. Link Professor and Director of the Wake Forest Institute for Regenerative Medicine and W. Boyce Professor and Chair, Department of Urology, and G. Link Professor and Director, Wake Forest Institute for Regenerative Medicine, Wake Forest University. Winston Salem, North Carolina, USA

PART ONE: INTRODUCTION TO STEM CELLS
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

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

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

4. Embryonic Stem Cells in Perspective
4.1 Embryonic Stem Cells in Perspective

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

PART TWO: BASIC BIOLOGY/MECHANISMS
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

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

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 ß-1
8.10 CKIs and Notch
8.11 Summary and Future Directions

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

PART THREE: TISSUE AND ORGAN DEVELOPMENT
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

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

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

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

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 Mammal
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

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

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

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

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

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

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

21. Stem Cells and the Regenerating Heart
21.1 Introduction
21.2 Recruiting Circulating Stem Cell Reserves
21.3 The Elusive Cardiac Stem Cell
21.4 Evolving Concepts of Regeneration

22. Cell Lineages and Stem Cells in the Embryonic Kidney
22.1 The Anatomy of Kidney Development
22.2 Genes that Control Early Kidney Development
22.3 The Establishment of Additional Cell Lineages
22.4 What Constitutes a Renal Stem Cell?

23. Adult Liver Stem Cells
23.1 Organization and Functions of Adult Mammalian Liver
23.2 Liver Stem Cells

24. Pancreatic Stem Cells
24.1 Introduction
24.2 Definition of Stem Cells and of Progenitor Cells
24.3 Progenitor Cells During Embryonic Development of the Pancreas
24.4 Progenitor Cells in the Adult Pancreas
24.5 Forcing Other Tissues to Adopt a Pancreatic Phenotype
24.6 In Vitro Studies
24.7 Summary

25. Stem Cells in the Gastrointestinal Tract
25.1 Introduction
25.2 Gastrointestinal Mucosa Contains Multiple Lineages
25.3 Epithelial Cell Lineages Originate from a Common Precursor Cell
25.4 Single Intestinal Stem Cells Regenerate Whole Crypts Containing all Epithelial Lineages
25.5 Mouse Aggregation Chimeras Show that Intestinal Crypts are Clonal Populations
25.6 Somatic Mutations in Stem Cells Reveal Stem Cell Hierarchy and Clonal Succession
25.7 Human Intestinal Crypts Contain Multiple Epithelial Cell Lineages Derived from a Single Stem Cell
25.8 Bone Marrow Stem Cells Contribute to Gut Repopulation After Damage
25.9 Gastrointestinal Stem Cells Occupy a Niche Maintained by ISEMFs in the Lamina Propria
25.10 Multiple Molecules Regulate Gastrointestinal Development, Proliferation, and Differentiation
25.11 Wnt/ß-Catenin Signaling Pathway Controls Intestinal Stem Cell Function
25.12 Transcription Factors Define Regional Gut Specification and Intestinal Stem Cell Fate
25.13 Gastrointestinal Neoplasms Originate in Stem Cell Populations
25.14 Summary

PART FOUR: METHODS
26. Induced Pluripotent Stem Cells
26.1 Generation of iPS Cells
26.2 Molecular Mechanisms in iPS Cell Induction
26.3 Recapitulation of Disease Ontology and Drug Screening
26.4 iPS Cell Banking
26.5 Safety Concerns for Medical Application
26.6 Medical Application
26.7 Direct Fate Switch
26.8 Conclusion

27. Embryonic Stem Cells: Derivation and Properties
27.1 Derivation of Embryonic Stem Cells
27.2 Culture of Embryonic Stem Cells
27.3 Developmental Potential of Embryonic Stem Cells
27.4 Conclusion

28. Isolation and Maintenance of Murine Embryonic Stem Cells
28.1 Introduction
28.2 Maintenance of Embryonic Stem Cells
28.3 Media
28.4 Sera
28.5 Colony-Forming Assay for Testing Culture Conditions
28.6 Embryonic Stem Cell Passage Culture
28.7 Isolation of New Embryonic STEM Cell Lines
28.8 Method for Deriving Embryonic Stem Cells
28.9 Summary

29. Approaches for Derivation and Maintenance of Human Embryonic Stem Cells: Detailed Procedures and Alternatives
29.1 Introduction
29.2 Setting Up the Lab
29.3 Preparing and Screening Reagents
29.4 Mechanical Passaging of hES Cell Colonies
29.5 Derivation of hES Cells
29.6 Maintenance of Established hES Cell Cultures
29.7 Freezing hES Cells
29.8 Thawing hES Cells
29.9 hES Cell Quality Control

30. Derivation and Differentiation of Human Embryonic Germ Cells
30.1 Introduction
30.2 Human Embryonic Germ Cell Derivation
30.3 Embryoid Body-Derived Cells

31. Genomic Reprogramming
31.1 Introduction
31.2 Genomic Reprogramming in Germ Cells
31.3 Reprogramming Somatic Nuclei
31.4 Conclusions

PART FIVE: APPLICATIONS
32. Neural Stem Cells – Therapeutic Applications in Neurodegenerative Diseases
32.1 Introduction
32.2 Definition of Neural Stem Cells
32.3 Therapeutic Potential of Neural Stem Cells
32.4 Gene Therapy Using Neural Stem Cells
32.5 Cell Replacement Using Neural Stem Cells
32.6 ‘Global’ Cell Replacement Using Neural Stem Cells
32.7 Neural Stem Cells Display an Inherent Mechanism for Rescuing Dysfunctional Neurons
32.8 Neural Stem Cells as the Glue That Holds Multiple Therapies Together
32.9 Summary

33. Adult Progenitor Cells as a Potential Treatment for Diabetes
33.1 Importance of ß-Cell Replacement Therapy for Diabetes and the Shortage of Insulin-Producing Cells
33.2 Potential of Adult Stem-Progenitor Cells as a Source of Insulin-Producing Cells
33.3 Defining ß-Cells, Stem Cells, and Progenitor Cells
33.4 New ß-Cells are Formed Throughout Adult Life
33.5 What is the Cellular Origin of Adult Islet Neogenesis?
33.6 Transdifferentiation of Nonislet Cells to Islet Cells
33.7 Pancreatic Acinar Cell Transdifferentiation
33.8 Bone Marrow Cells as a Source of Insulin-Producing Cells
33.9 Liver as a Source of Insulin-Producing Cells
33.10 Engineering Other Non-ß-Cells to Produce Insulin
33.11 Attempts to Deliver Insulin Through Constitutive Rather Than Regulated Secretion
33.12 Summary

34. Burns and Skin Ulcers
34.1 Introduction
34.2 Burns and Skin Ulcers – The Problem
34.3 Epidermal Stem Cells
34.4 Stem Cells in Burns and Skin Ulcers – Current Use
34.5 Recent and Future Developments

35. Stem Cells and Heart Disease
35.1 Heart: A Self-renewing Organ
35.2 Distribution of CSCS in the Heart
35.3 Repair of Myocardial Damage by Nonresident Primitive Cells
35.4 Repair of Myocardial Damage by Resident Primitive Cells
35.5 Myocardial Regeneration in Humans

36. Stem Cells for the Treatment of Muscular Dystrophy
36.1 Introduction
36.2 Myoblast Transplantation – Past Failure and New Hope
36.3 Unconventional Myogenic Progenitors
36.4 Pluripotent Stem Cells for Future Cell-Based Therapies
36.5 Future Perspectives

37. Cell Therapy for Liver Disease: From Hepatocytes to Stem Cells
37.1 Introduction
37.2 Background Studies
37.3 Integration of Hepatocytes Following Transplantation
37.4 Clinical Hepatocyte Transplantation
37.5 Hepatocyte Bridge
37.6 Hepatocyte Transplantation in Acute Liver Failure
37.7 Hepatocyte Transplantation for Metabolic Liver Disease
37.8 Hepatocyte Transplantation – Novel Uses, Challenges, and Future Directions
37.9 Conclusion

38. Orthopedic Applications of Stem Cells
38.1 Introduction
38.2 Bone
38.3 Cartilage
38.4 Meniscus
38.5 Ligaments and Tendons
38.6 Spine
38.7 Summary

39. Embryonic Stem Cells in Tissue Engineering
39.1 Introduction
39.2 Tissue Engineering Principles and Perspectives
39.3 Limitations and Hurdles of Using ES Cells in Tissue Engineering
39.4 Summary

PART SIX: REGULATION AND ETHICS
40. Ethical Considerations
40.1 Introduction
40.2 Is it Morally Permissible to Destroy a Human Embryo?
40.3 Should we Postpone hES Cell Research?
40.4 Can We Benefit from Others’ Destruction of Embryos?
40.5 Can We Create an Embryo to Destroy it?
40.6 Should We Clone Human Embryos?
40.7 What Ethical Guidelines Should Govern hES Cell and Therapeutic Cloning Research?
40.8 Summary

41. Overview of the FDA Regulatory Process
41.1 Introduction and Chapter Overview
41.2 Brief Legislative History of FDA
41.3 Laws, Regulations, and Guidance
41.4 FDA Organization and Jurisdictional Issues
41.5 Approval Mechanisms and Clinical Studies
41.6 Meetings with Industry, Professional Groups, and Sponsors
41.7 Regulations and Guidance of Special Interest for Regenerative Medicine
41.8 FDA’s Standards Development Program
41.9 Advisory Committee Meetings
41.10 FDA Research and Critical Path Science
41.11 Other Communication Efforts
41.12 Conclusion

42. It’s Not about Curiosity, It’s about Cures: Stem Cell Research – People Help Drive Progress
42.1 Choosing Life
42.2 Size of the Promise
42.3 Personal Promises Fuel Progress
42.4 Hope Versus Hype
42.5 Giving Life
42.6 People Drive Progress
42.7 Better Health for All

Book Reviews

Reviews of the previous edition:
"…serves the needs of the evolving population of scientists, researchers, practitioners, and students embracing the latest advances in stem cells…From basic biology, 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."—Anticancer Research 34, 2014

"This book offers a thorough review of current research and therapeutic potential in the field of stem cell biology. The focus is on the therapeutic potential of stem cells, with the discussion of the current state of stem cell knowledge and stem cell therapies in various organs and tissues…any scientists interested in studying the field would benefit from this book's thorough treatment of the subject."Rating: 4 Stars —Doody.com, March 7, 2014

ISBN: 9780443154201

Page Count: 600

Retail Price :

researchers, grad students, and professionals working with human stem cells in biology, tissue engineering, genetics, cancer research, virology, immunology, and biotechnology