E-Book, Englisch, 680 Seiten
Lanza / Gearhart / Hogan Essentials of Stem Cell Biology
2. Auflage 2009
ISBN: 978-0-08-088497-4
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark
E-Book, Englisch, 680 Seiten
ISBN: 978-0-08-088497-4
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark
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 that are embracing the latest advances in stem cells. Representing the combined effort of seven 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, methods to 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.
Selected for inclusion in Doody's Core Titles 2013, an essential collection development tool for health sciences librariesContributions by Nobel Laureates and leading international investigatorsIncludes two entirely new chapters devoted exclusively to induced pluripotent stem (iPS) cells written by the scientists who made the breakthroughEdited 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 debatePresented in full color with glossary, highlighted terms, and bibliographic entries replacing references
Autoren/Hrsg.
Weitere Infos & Material
1;Front Cover;1
2;Essentials of Stem Cell Biology;4
3;Copyright Page;5
4;Contents;6
5;Contributors;10
6;Preface;16
7;Foreword;18
8;Why Stem Cell Research;20
9;A New Path: Induced Pluripotent Stem Cells;22
10;"Stemness": Definitions, Criteria, and Standards;24
11;Part I: Introduction to Stem Cells;32
11.1;Chapter 1. Pluripotential Stem Cells from Vertebrate Embryos: Present Perspective and Future Challenges;34
11.1.1;INTRODUCTION;34
11.1.2;TERMINOLOGY;35
11.1.3;ES-LIKE CELLS IN OTHER SPECIES;36
11.1.4;EMBRYONIC GERM CELLS;37
11.1.5;FUTURE CHALLENGES;38
11.1.6;BIOLOGY OF ES AND ES-LIKE CELLS;38
11.1.7;STEM CELL THERAPY;40
11.1.8;CONCLUSIONS;42
11.1.9;KEY WORDS;42
11.1.10;FURTHER READING;42
11.2;Chapter 2. Embryonic Stem Cells in Perspective;44
11.2.1;FURTHER READING;45
11.3;Chapter 3. The Development of Epithelial Stem Cell Concepts;48
11.3.1;INTRODUCTION;48
11.3.2;A DEFINITION OF STEM CELLS;49
11.3.3;HIERARCHICALLY ORGANIZED STEM CELL POPULATIONS;50
11.3.4;SKIN STEM CELLS;51
11.3.5;THE INTESTINAL STEM CELL SYSTEM;53
11.3.6;STEM CELL ORGANIZATION ON THE TONGUE;54
11.3.7;GENERALIZED SCHEME;55
11.3.8;SUMMARY;56
11.3.9;KEY WORDS;57
11.3.10;FURTHER READING;58
11.4;Chapter 4. Direct Reprogramming of Somatic Cells to a Pluripotent State;60
11.4.1;INTRODUCTION;60
11.4.2;KEY WORDS;62
11.4.3;FURTHER READING;62
11.5;Chapter 5. Clinical Translation of Stem Cells;64
11.5.1;INTRODUCTION;64
11.5.2;CELL PROCESSING AND MANUFACTURING;64
11.5.3;STUDIES WITH STEM CELLS IN ANIMAL MODELS;65
11.5.4;CLINICAL TRIALS WITH STEM CELLS IN PATIENTS;65
11.5.5;CONCLUSIONS;66
11.5.6;FURTHER READING;66
12;Part II: Basic Biology/Mechanisms;68
12.1;Chapter 6. Molecular Basis of Pluripotency;70
12.1.1;INTRODUCTION;70
12.1.2;CELLULAR MODELS OF PLURIPOTENCY;70
12.1.3;THE EMBRYONIC STEM CELL ENVIRONMENT: CYTOKINES AND PLURIPOTENCY;71
12.1.4;CYTOKINE-RECEPTOR BINDING ON ES CELLS: MULTIPLE RELAY STATIONS;72
12.1.5;SIGNAL TRANSDUCTION: CASCADES TO THE STEM CELL NUCLEUS;73
12.1.6;STATS: LATENT TRANSCRIPTION FACTORS TRANSMITTING SIGNALS;73
12.1.7;STAT3;74
12.1.8;SHP-2/ERK SIGNALING;75
12.1.9;FGF4 AND ERK;76
12.1.10;WNT SIGNALING;76
12.1.11;THE TGFß SIGNALING PATHWAY;76
12.1.12;THE PI3K/AKT SIGNALING PATHWAY PARTICIPATES IN ES CELL PROLIFERATION, SURVIVAL, AND PLURIPOTENCY;77
12.1.13;THE NEW PARADIGM OF EMBRYONIC STEM CELL RENEWAL;78
12.1.14;INTRINSIC DETERMINANTS OF PLURIPOTENCY;79
12.1.15;OCT4 IS A KEY TRANSCRIPTION FACTOR FOR PLURIPOTENCY;79
12.1.16;OCT4 EXPRESSION;79
12.1.17;OCT4 ACTIVITY IN ASSAYS;80
12.1.18;REGULATION OF OCT4 EXPRESSION;81
12.1.19;OCT4 TARGET GENES;82
12.1.20;OCT4 DOES NOT PLAY SOLO: SOX2;82
12.1.21;FOXD3;84
12.1.22;NANOG;84
12.1.23;THE CORE TRANSCRIPTIONAL REGULATORY CIRCUITRY CONTROLLING ES CELL IDENTITY;86
12.1.24;THE ROLE OF MICRO-RNAS IN PLURIPOTENCY;86
12.1.25;DGCR8;87
12.1.26;THE CHROMATIN STATUS DEFINING STEM CELL IDENTITY;87
12.1.27;REPROGRAMMING OF SOMATIC CELLS TO A PLURIPOTENT STATE: IPS VERSUS ES;88
12.1.28;CONCLUSIONS;89
12.1.29;KEY TERMS;90
12.1.30;FURTHER READING;90
12.2;Chapter 7. Stem Cell Niches;92
12.2.1;INTRODUCTION;92
12.2.2;STEM CELL NICHE HYPOTHESIS;92
12.2.3;STEM CELL NICHES IN THE DROSOPHILA GERMLINE;92
12.2.4;STEM CELL NICHES WITHIN MAMMALIAN TISSUES;96
12.2.5;SUMMARY;101
12.2.6;ACKNOWLEDGMENTS;102
12.2.7;KEY WORDS;103
12.2.8;FURTHER READING;103
12.3;Chapter 8. Mechanisms of Stem Cell Self-renewal;104
12.3.1;INTRODUCTION;104
12.3.2;SELF-RENEWAL OF PLURIPOTENT STEM CELLS;104
12.3.3;MOLECULAR MECHANISM FOR RETENTION OF EMBRYONIC STEM CELL SELF-RENEWAL;105
12.3.4;EPIGENETIC REGULATION OF SELF-RENEWAL;109
12.3.5;SELF-RENEWAL OF HUMAN EMBRYONIC STEM CELLS;110
12.3.6;SUMMARY;110
12.3.7;KEY WORDS;110
12.3.8;FURTHER READING;110
12.4;Chapter 9. Cell Cycle Regulators in Adult Stem Cells;112
12.4.1;INTRODUCTION;112
12.4.2;CELL CYCLE KINETICS OF STEM CELLS IN VIVO;112
12.4.3;STEM CELL EXPANSION EX VIVO;113
12.4.4;MAMMALIAN CELL CYCLE REGULATION AND CYCLIN-DEPENDENT KINASE INHIBITORS;113
12.4.5;ROLES OF CYCLIN-DEPENDENT KINASE INHIBITORS IN STEM CELL REGULATION;114
12.4.6;SUMMARY;117
12.4.7;ACKNOWLEDGMENTS;117
12.4.8;KEY WORDS;117
12.4.9;FURTHER READING;117
12.5;Chapter 10. Epigenetic Mechanisms of Cellular Memory during Development;120
12.5.1;INTRODUCTION;120
12.5.2;CHROMATIN-MODIFYING FACTORS;123
12.5.3;ATPASE CHROMATIN-REMODELING COMPLEXES;125
12.5.4;EPIGENETIC PROCESSES;126
12.5.5;X-CHROMOSOME INACTIVATION;128
12.5.6;MONOALLELIC EXPRESSION: GENOMIC IMPRINTING AND ALLELIC EXCLUSION;131
12.5.7;SUMMARY AND FUTURE DIRECTIONS;133
12.5.8;KEY WORDS;134
12.5.9;FURTHER READING;134
12.6;Chapter 11. Cell Fusion and the Differentiated State;136
12.6.1;INTRODUCTION;136
12.6.2;HYBRID CELLS AND DIFFERENTIATED PHENOTYPES;136
12.6.3;HYBRIDS OF PLURIPOTENT CELLS;137
12.6.4;REPROGRAMMING SOMATIC CELL NUCLEI WITH EC, ES, OR EG CELL CYTOPLASM;138
12.6.5;CELL FUSION AND THE DEMONSTRATION OF STEM CELL PLASTICITY;139
12.6.6;SUMMARY;140
12.6.7;ACKNOWLEDGMENTS;140
12.6.8;KEY WORDS;140
12.6.9;FURTHER READING;141
12.7;Chapter 12. How Cells Change Their Phenotype;142
12.7.1;INTRODUCTION;142
12.7.2;METAPLASIA AND TRANSDIFFERENTIATION;142
12.7.3;WHY STUDY TRANSDIFFERENTIATION?;142
12.7.4;EXAMPLES OF THE PHENOMENON;142
12.7.5;DEDIFFERENTIATION AS A PREREQUISITE FOR TRANSDIFFERENTIATION;145
12.7.6;HOW TO CHANGE A CELL'S PHENOTYPE EXPERIMENTALLY;146
12.7.7;SUMMARY;147
12.7.8;ACKNOWLEDGMENTS;147
12.7.9;KEY WORDS;147
12.7.10;FURTHER READING;147
13;Part III: Tissue and Organ Development;148
13.1;Chapter 13. Differentiation in Early Development;150
13.1.1;INTRODUCTION;150
13.1.2;PRE-IMPLANTATION DEVELOPMENT;150
13.1.3;FROM IMPLANTATION TO GASTRULATION;156
13.1.4;ACKNOWLEDGMENTS;160
13.1.5;KEY WORDS;160
13.1.6;FURTHER READING;160
13.2;Chapter 14. Primordial Germ Cells in Mouse and Human;162
13.2.1;INTRODUCTION;162
13.2.2;ORIGIN OF THE GERM CELL LINEAGE;162
13.2.3;MIGRATION;164
13.2.4;GERM CELLS IN THE GENITAL RIDGE;164
13.2.5;EMBRYONIC GERM CELLS;166
13.2.6;SUMMARY;166
13.2.7;KEY WORDS;167
13.2.8;FURTHER READING;167
13.3;Chapter 15. Stem Cells in Extraembryonic Lineages;168
13.3.1;INTRODUCTION;168
13.3.2;TROPHOBLAST LINEAGE;168
13.3.3;TROPHOBLAST STEM CELL LINES;172
13.3.4;EXTRAEMBRYONIC ENDODERM LINEAGE;174
13.3.5;SUMMARY;175
13.3.6;KEY WORDS;175
13.3.7;FURTHER READING;175
13.4;Chapter 16. Amniotic Fluid-Derived Pluripotential Cells;176
13.4.1;INTRODUCTION;176
13.4.2;AMNIOTIC FLUID AND AMNIOCENTESIS;176
13.4.3;ISOLATION AND CHARACTERIZATION OF PROGENITOR CELLS;177
13.4.4;DIFFERENTIATION POTENTIAL OF AMNIOTIC PROGENITOR CELLS;177
13.4.5;IN VIVO BEHAVIOR OF AMNIOTIC FLUID STEM CELLS;180
13.4.6;FUTURE DIRECTIONS;180
13.4.7;SUMMARY;180
13.4.8;KEY WORDS;181
13.4.9;FURTHER READING;181
13.5;Chapter 17. Cord Blood Hematopoietic Stem and Progenitor Cells;182
13.5.1;INTRODUCTION;182
13.5.2;CHARACTERISTICS AND CRYOPRESERVATION OF CORD BLOOD STEM AND PROGENITOR CELLS;182
13.5.3;CORD BLOOD TRANSPLANTATION PROBLEMS AND POSSIBLE COUNTERMEASURES;183
13.5.4;HOMING OF STEM AND PROGENITOR CELLS;185
13.5.5;SUMMARY;186
13.5.6;KEY WORDS;186
13.5.7;FURTHER READING;186
13.6;Chapter 18. Neurogenesis in the Vertebrate Embryo;188
13.6.1;INTRODUCTION;188
13.6.2;EMBRYONIC INDUCTION AND THE ESTABLISHMENT OF NEURAL TISSUE;188
13.6.3;MOLECULAR BASES OF NEURAL INDUCTION;188
13.6.4;NEURAL PATTERNING;191
13.6.5;PRONEURAL GENE EXPRESSION;195
13.6.6;NEGATIVE REGULATORS OF PRONEURAL ACTIVITY;195
13.6.7;REGULATION OF NEURONAL DIFFERENTIATION BY REST/NRSF;197
13.6.8;SWITCH FROM NEUROGENESIS TO GLIOGENESIS;197
13.6.9;SUMMARY;197
13.6.10;KEY WORDS;198
13.6.11;FURTHER READING;198
13.7;Chapter 19. The Nervous System;200
13.7.1;INTRODUCTION;200
13.7.2;NEURAL DEVELOPMENT;200
13.7.3;NEURAL STEM CELLS;201
13.7.4;NEURAL DIFFERENTIATION OF MOUSE EMBRYONIC STEM CELLS;201
13.7.5;NEURAL DIFFERENTIATION OF HUMAN AND NONHUMAN PRIMATE ES CELLS;206
13.7.6;DEVELOPMENTAL PERSPECTIVE;207
13.7.7;THERAPEUTIC PERSPECTIVES;207
13.7.8;CONCLUSION;208
13.7.9;KEY WORDS;209
13.7.10;FURTHER READING;209
13.8;Chapter 20. Neuronal Progenitors in the Adult Brain: From Development to Regulation;210
13.8.1;INTRODUCTION;210
13.8.2;HISTORY OF STEM CELLS IN THE ADULT CENTRAL NERVOUS SYSTEM;210
13.8.3;GLIAL CHARACTERISTICS OF NEURAL STEM CELLS;210
13.8.4;ADULT NEUROGENESIS IN VIVO;211
13.8.5;SUMMARY;213
13.8.6;KEY WORDS;213
13.8.7;FURTHER READING;213
13.9;Chapter 21. Sensory Epithelium of the Eye and Ear: Update of Retinal Stem Cell Research 2003 to the Present;216
13.9.1;INTRODUCTION;216
13.9.2;MUELLER GLIA AS A SOURCE OF NEW RETINAL NEURONS;216
13.9.3;EMBRYONIC STEM CELLS AS A SOURCE OF RETINAL NEURONS;217
13.9.4;KEY WORDS;218
13.9.5;FURTHER READING;219
13.10;Chapter 22. Epithelial Hair Follicle Stem Cells;220
13.10.1;INTRODUCTION;220
13.10.2;A BRIEF INTRODUCTION TO MOUSE SKIN ORGANIZATION;220
13.10.3;THE BULGE AS A RESIDENCE OF HAIR FOLLICLE STEM CELLS;222
13.10.4;MODELS OF HAIR FOLLICLE STEM CELL ACTIVATION;224
13.10.5;MOLECULAR FINGERPRINT OF THE BULGE: PUTATIVE STEM CELL MARKERS;225
13.10.6;CELL SIGNALING IN HAIR FOLLICLE STEM CELLS;226
13.10.7;COMMENTARY AND FUTURE DIRECTIONS;227
13.10.8;KEY WORDS;228
13.10.9;FURTHER READING;228
13.11;Chapter 23. The Ontogeny of the Hematopoietic System;230
13.11.1;HISTORIC PERSPECTIVE;230
13.11.2;SITES OF INITIATION OF PRIMITIVE AND DEFINITIVE HEMATOPOIESIS AND VASCULOGENESIS;230
13.11.3;STEM CELL MIGRATION TO LATER SITES OF HEMATOPOIESIS;236
13.11.4;CELL MIGRATION TO PRIMARY LYMPHOID ORGANS;237
13.11.5;KEY WORDS;240
13.11.6;FURTHER READING;240
13.12;Chapter 24. Hematopoietic Stem Cells;242
13.12.1;EMBRYONIC STEM CELLS AND EMBRYONIC HEMATOPOIESIS;242
13.12.2;BLOOD FORMATION IN EMBRYOID BODIES;243
13.12.3;TRANSFORMATION OF AN EB-DERIVED HSC BY BCR/ABL;243
13.12.4;PROMOTING HEMATOPOIETIC ENGRAFTMENT WITH STAT5 AND HOXB4;243
13.12.5;PROMOTING BLOOD FORMATION IN VITRO WITH EMBRYONIC MORPHOGENS;245
13.12.6;KEY WORDS;245
13.12.7;FURTHER READING;246
13.13;Chapter 25. Red Blood Cells;248
13.13.1;ERYTHROPOIESIS;248
13.13.2;ERYTHROCYTES GENERATED FROM ADULT STEM CELLS IN VITRO;248
13.13.3;ERYTHROCYTES GENERATED FROM MOUSE EMBRYONIC STEM CELLS;249
13.13.4;ERYTHROCYTES GENERATED FROM HUMAN EMBRYONIC STEM CELLS;249
13.13.5;ENUCLEATION OF ERYTHROID CELLS;252
13.13.6;SUMMARY;253
13.13.7;KEY WORDS;253
13.13.8;FURTHER READING;253
13.14;Chapter 26. Cell Differentiation in the Skeleton;254
13.14.1;INTRODUCTION;254
13.14.2;SKELETOGENESIS;254
13.14.3;CHONDROCYTE DIFFERENTIATION;255
13.14.4;OSTEOBLAST DIFFERENTIATION;256
13.14.5;KEY WORDS;257
13.14.6;FURTHER READING;257
13.15;Chapter 27. Human Vascular Progenitor Cells;258
13.15.1;HUMAN VASCULAR DEVELOPMENT, MAINTENANCE AND RENEWAL;258
13.15.2;HUMAN EMBRYONIC STEM CELLS AS A SOURCE FOR VASCULAR PROGENITORS;260
13.15.3;ACKNOWLEDGMENTS;263
13.15.4;KEY WORDS;263
13.15.5;FURTHER READING;263
13.16;Chapter 28. Multipotent Adult Progenitor Cells;264
13.16.1;INTRODUCTION;264
13.16.2;ISOLATION AND PHENOTYPIC CHARACTERIZATION OF MULTIPOTENT ADULT PROGENITOR CELLS;264
13.16.3;IN VITRO DIFFERENTIATION POTENTIAL OF MULTIPOTENT ADULT PROGENITOR CELLS;265
13.16.4;IN VIVO ENGRAFTMENT OF MULTIPOTENT ADULT PROGENITOR CELLS;266
13.16.5;MULTIPOTENT ADULT PROGENITOR CELLS IN ISCHEMIA MODELS;266
13.16.6;SYSTEMIC TRANSPLANTATION OF MULTIPOTENT ADULT PROGENITOR CELLS;267
13.16.7;OTHER ADULT STEM CELLS WITH GREATER DIFFERENTIATION POTENTIAL;268
13.16.8;POSSIBLE MECHANISMS UNDERLYING THE GREATER POTENCY OF MULTIPOTENT ADULT PROGENITOR CELLS;268
13.16.9;KEY WORDS;270
13.16.10;FURTHER READING;271
13.17;Chapter 29. Mesenchymal Stem Cells;274
13.17.1;INTRODUCTION;274
13.17.2;TISSUE-ENGINEERED REGENERATION;276
13.17.3;ISOLATING AND CULTURING MESENCHYMAL STEM CELLS;277
13.17.4;TISSUE-ENGINEERING USES OF MESENCHYMAL STEM CELLS;277
13.17.5;SUMMARY;279
13.17.6;ACKNOWLEDGMENTS;279
13.17.7;KEY WORDS;279
13.17.8;FURTHER READING;279
13.18;Chapter 30. Skeletal Muscle Stem Cells;280
13.18.1;INTRODUCTION;280
13.18.2;SATELLITE CELLS IDENTIFICATION;280
13.18.3;SATELLITE CELL HETEROGENEITY;282
13.18.4;SATELLITE CELL SELF-RENEWAL;283
13.18.5;INTRINSIC REGULATION OF SATELLITE CELLS;284
13.18.6;EXTRINSIC REGULATION OF SATELLITE CELLS;285
13.18.7;SUMMARY;288
13.18.8;ACKNOWLEDGMENTS;288
13.18.9;KEY WORDS;288
13.18.10;FURTHER READING;288
13.19;Chapter 31. Stem Cells and the Regenerating Heart;290
13.19.1;INTRODUCTION;290
13.19.2;EVOLVING CONCEPTS OF REGENERATION;292
13.19.3;ACKNOWLEDGMENTS;294
13.19.4;KEY WORDS;294
13.19.5;FURTHER READING;294
13.20;Chapter 32. Potential of Embryonic and Induced Pluripotent Stem Cell Differentiation Culture for Vascular Biology;296
13.20.1;INTRODUCTION;296
13.20.2;CULTURES FOR EMBRYONIC STEM CELL DIFFERENTIATION;296
13.20.3;MARKERS FOR DEFINING INTERMEDIATE STAGES DURING ENDOTHELIAL CELL DIFFERENTIATION;297
13.20.4;UTILITY OF EMBRYONIC STEM CELL CULTURE FOR CELL BIOLOGY OF ENDOTHELIAL CELLS;298
13.20.5;ENDOTHELIAL CELL DIVERSIFICATION;299
13.20.6;CONCLUDING REMARKS;301
13.20.7;KEY WORDS;302
13.20.8;FURTHER READING;302
13.21;Chapter 33. Cell Lineages and Stem Cells in the Embryonic Kidney;304
13.21.1;INTRODUCTION;304
13.21.2;THE ANATOMY OF KIDNEY DEVELOPMENT;304
13.21.3;GENES THAT CONTROL EARLY KIDNEY DEVELOPMENT;307
13.21.4;THE ESTABLISHMENT OF ADDITIONAL CELL LINEAGES;310
13.21.5;WHAT CONSTITUTES A RENAL STEM CELL?;312
13.21.6;ACKNOWLEDGMENTS;313
13.21.7;KEY WORDS;313
13.21.8;FURTHER READING;313
13.22;Chapter 34. Adult Liver Stem Cells;316
13.22.1;INTRODUCTION;316
13.22.2;ORGANIZATION AND FUNCTIONS OF ADULT MAMMALIAN LIVER;316
13.22.3;LIVER STEM CELLS;317
13.22.4;IMMORTAL LIVER PROGENITOR CELL LINES;323
13.22.5;KEY WORDS;329
13.22.6;FURTHER READING;329
13.23;Chapter 35. Pancreatic Stem Cells;330
13.23.1;INTRODUCTION;330
13.23.2;DEFINITION OF STEM CELLS AND OF PROGENITOR CELLS;330
13.23.3;PROGENITOR CELLS DURING EMBRYONIC DEVELOPMENT OF THE PANCREAS;331
13.23.4;PROGENITOR CELLS IN THE ADULT PANCREAS;332
13.23.5;FORCING OTHER TISSUES TO ADOPT A PANCREATIC PHENOTYPE;334
13.23.6;IN VITRO STUDIES;335
13.23.7;SUMMARY;336
13.23.8;KEY WORDS;336
13.23.9;FURTHER READING;336
13.24;Chapter 36. Stem Cells in the Gastrointestinal Tract;338
13.24.1;INTRODUCTION;338
13.24.2;GASTROINTESTINAL MUCOSA CONTAINS MULTIPLE LINEAGES;339
13.24.3;EPITHELIAL CELL LINEAGES ORIGINATE FROM A COMMON PRECURSOR CELL;339
13.24.4;SINGLE INTESTINAL STEM CELLS REGENERATE WHOLE CRYPTS CONTAINING ALL EPITHELIAL LINEAGES;340
13.24.5;MOUSE AGGREGATION CHIMERAS SHOW THAT INTESTINAL CRYPTS ARE CLONAL POPULATIONS;340
13.24.6;SOMATIC MUTATIONS IN STEM CELLS REVEAL STEM CELL HIERARCHY AND CLONAL SUCCESSION;341
13.24.7;HUMAN INTESTINAL CRYPTS CONTAIN MULTIPLE EPITHELIAL CELL LINEAGES DERIVED FROM A SINGLE STEM CELL;344
13.24.8;BONE MARROW STEM CELLS CONTRIBUTE TO GUT REPOPULATION AFTER DAMAGE;345
13.24.9;GASTROINTESTINAL STEM CELLS OCCUPY A NICHE MAINTAINED BY INTESTINAL SUBEPITHELIAL MYOFIBROBLASTS IN THE LAMINA PROPRIA;348
13.24.10;MANY SIGNALING PATHWAYS REGULATE GASTROINTESTINAL DEVELOPMENT, PROLIFERATION, AND DIFFERENTIATION;350
13.24.11;WNT/ß-CATENIN SIGNALING PATHWAY MAINTAINS THE PROLIFERATIVE COMPARTMENT OF INTESTINAL CRYPTS;350
13.24.12;WNT TARGETS EPHB DETERMINE CELL POSITIONING ALONG THE CRYPT AXIS;351
13.24.13;NOTCH SIGNALING IS ALSO TO MAINTAIN THE PROLIFERATIVE COMPARTMENT OF INTESTINAL CRYPTS, AND DETERMINES CELL FATE;352
13.24.14;BONE MORPHOGENIC PATHWAY SIGNALING REGULATES PROLIFERATION ALONG THE INTESTINAL CRYPT AXIS;353
13.24.15;HEDGEHOG SIGNALING PATTERNS THE CRYPT AXIS;353
13.24.16;HOX GENES DEFINE REGIONAL GUT SPECIFICATION;353
13.24.17;GASTROINTESTINAL NEOPLASMS ORIGINATE IN STEM CELL POPULATIONS;353
13.24.18;SUMMARY;357
13.24.19;KEY WORDS;357
13.24.20;FURTHER READING;358
14;Part IV: Methods;360
14.1;Chapter 37. Induced Pluripotent Stem Cell Derivation;362
14.1.1;INTRODUCTION;362
14.1.2;MATERIALS;362
14.1.3;PREPARING TRANSGENE-EXPRESSING LENTIVIRUS;363
14.1.4;REPROGRAMMING HUMAN FORESKIN FIBROBLASTS;366
14.1.5;ACKNOWLEDGMENTS;368
14.1.6;KEY WORDS;368
14.1.7;FURTHER READING;368
14.2;Chapter 38. Characteristics and Characterization of Human Pluripotent Stem Cells;370
14.2.1;INTRODUCTION;370
14.2.2;CHARACTERIZATION OF PLURIPOTENT CELLS;372
14.2.3;SUMMARY;373
14.2.4;KEY WORDS;374
14.2.5;FURTHER READING;374
14.3;Chapter 39. Isolation and Maintenance of Murine Embryonic Stem Cells;376
14.3.1;INTRODUCTION;376
14.3.2;MAINTENANCE OF EMBRYONIC STEM CELLS;376
14.3.3;MEDIA;377
14.3.4;SERA;377
14.3.5;COLONY-FORMING ASSAY FOR TESTING CULTURE CONDITIONS;377
14.3.6;EMBRYONIC STEM CELL PASSAGE CULTURE;378
14.3.7;ISOLATION OF NEW EMBRYONIC STEM CELL LINES;378
14.3.8;METHOD FOR DERIVATION OF EMBRYONIC STEM CELLS;379
14.3.9;SUMMARY;380
14.3.10;FURTHER READING;380
14.4;Chapter 40. Isolation, Characterization and Maintenance of Primate Embryonic Stem Cells;382
14.4.1;INTRODUCTION;382
14.4.2;WHAT ARE PRIMATE EMBRYONIC STEM CELLS?;383
14.4.3;TECHNIQUES FOR THE DERIVATION OF HUMAN EMBRYONIC STEM CELL LINES;384
14.4.4;DERIVATION OF HUMAN EMBRYONIC STEM CELL SUBCLONES;388
14.4.5;METHODS FOR HUMAN EMBRYONIC STEM CELL CULTURE;389
14.4.6;PRIMATE VERSUS MOUSE EMBRYONIC STEM CELLS;391
14.4.7;PRIMATE EMBRYONIC STEM CELL DIFFERENTIATION SYSTEMS;393
14.4.8;ACKNOWLEDGMENTS;393
14.4.9;FURTHER READING;393
14.5;Chapter 41. Approaches for Derivation and Maintenance of Human Embryonic Stem Cells: Detailed Procedures and Alternatives;396
14.5.1;INTRODUCTION;396
14.5.2;SETTING UP THE LABORATORY;396
14.5.3;PREPARING AND SCREENING REAGENTS;397
14.5.4;PREPARING PRIMARY MOUSE EMBRYO FIBROBLAST (PMEF) FEEDERS;400
14.5.5;MECHANICAL PASSAGING OF HUMAN EMBRYONIC STEM CELL COLONIES;400
14.5.6;DERIVATION OF HUMAN EMBRYONIC STEM CELLS;402
14.5.7;MAINTENANCE OF ESTABLISHED HUMAN EMBRYONIC STEM CELL CULTURES;403
14.5.8;GLOSSARY TERMS;409
14.5.9;FURTHER READING;409
14.6;Chapter 42. Derivation and Differentiation of Human Embryonic Germ Cells;412
14.6.1;INTRODUCTION;412
14.6.2;HUMAN EMBRYONIC GERM CELL DERIVATION;413
14.6.3;EMBRYOID BODY-DERIVED CELLS;418
14.6.4;SUMMARY;421
14.6.5;KEY WORDS;421
14.6.6;FURTHER READING;421
14.7;Chapter 43. Growth Factors and the Serum-free Culture of Human Pluripotent Stem Cells;422
14.7.1;INTRODUCTION;422
14.7.2;MOUSE EMBRYONIC STEM CELLS;422
14.7.3;HUMAN EMBRYONAL CARCINOMA CELLS;423
14.7.4;HUMAN EMBRYONIC STEM CELLS;423
14.7.5;EXTRACELLULAR MATRIX COMPONENTS;425
14.7.6;FUTURE PROSPECTS;425
14.7.7;KEY WORDS;426
14.7.8;FURTHER READING;426
14.8;Chapter 44. Feeder-free Culture;428
14.8.1;INTRODUCTION;428
14.8.2;FEEDER-FREE CULTURE USING CONDITIONED MEDIUM AND MATRIGEL;428
14.8.3;FEEDER-FREE CULTURE USING CONDITIONED MEDIUM AND MATRIGEL OR LAMININ;431
14.8.4;FEEDER-FREE CULTURE USING DEFINED MEDIA AND MATRIGEL;432
14.8.5;MATERIALS FOR FEEDER-FREE HUMAN EMBRYONIC STEM CELL CULTURE;436
14.8.6;KEY WORDS;438
14.8.7;FURTHER READING;438
14.9;Chapter 45. Genetic Manipulation of Human Embryonic Stem Cells;440
14.9.1;INTRODUCTION;440
14.9.2;METHODS OF GENETIC MANIPULATION;440
14.9.3;GENETIC MODIFICATION APPROACHES;441
14.9.4;CONCLUSIONS;446
14.9.5;KEY WORDS;446
14.9.6;FURTHER READING;446
14.10;Chapter 46. Homologous Recombination in Human Embryonic Stem Cells;448
14.10.1;INTRODUCTION;448
14.10.2;TARGETED ABLATION OF THE HPRT1 GENE AS A TOOL TO OPTIMIZE HOMOLOGOUS RECOMBINATION EFFICIENCY;448
14.10.3;OCT4 EGFP/NEO KNOCKIN;450
14.10.4;TH EGFP KNOCKIN;451
14.10.5;CONCLUSIONS;452
14.10.6;ACKNOWLEDGMENTS;452
14.10.7;KEY WORDS;452
14.10.8;FURTHER READING;453
14.11;Chapter 47. Surface Antigen Markers;454
14.11.1;INTRODUCTION;454
14.11.2;CELL-SURFACE EMBRYONIC ANTIGENS OF THE LABORATORY MOUSE;454
14.11.3;HUMAN EMBRYONAL CARCINOMA AND EMBRYONIC STEM CELLS;455
14.11.4;SUMMARY;456
14.11.5;APPENDIX: METHODS;457
14.11.6;NOTES;458
14.11.7;SOLUTIONS AND NOTES;458
14.11.8;ACKNOWLEDGMENTS;459
14.11.9;KEY WORDS;459
14.11.10;FURTHER READING;459
14.12;Chapter 48. Lineage Marking;460
14.12.1;DEFINITIONS;460
14.12.2;QUESTIONS TO ASK;460
14.12.3;MARKERS AND LINEAGE MARKING;461
14.12.4;FUTURE DIRECTIONS;466
14.12.5;ACKNOWLEDGMENTS;466
14.12.6;KEY WORDS;466
14.12.7;FURTHER READING;466
14.13;Chapter 49. Genomic Reprogramming;468
14.13.1;INTRODUCTION;468
14.13.2;GENOMIC REPROGRAMMING IN GERM CELLS;468
14.13.3;REPROGRAMMING SOMATIC NUCLEI;472
14.13.4;CONCLUSIONS;472
14.13.5;KEY WORDS;473
14.13.6;FURTHER READING;473
14.14;Chapter 50. Isolation and Characterization of Hematopoietic Stem Cells;474
14.14.1;INTRODUCTION;474
14.14.2;ISOLATION OF HEMATOPOIETIC STEM CELLS FROM MICE;474
14.14.3;ISOLATION OF HEMATOPOIETIC STEM CELLS FROM HUMANS;477
14.14.4;HEMATOPOIETIC STEM CELLS AS A PARADIGM FOR STEM CELL BIOLOGY;478
14.14.5;ACKNOWLEDGMENT;478
14.14.6;KEY WORDS;478
14.14.7;FURTHER READING;478
14.15;Chapter 51. Microarray Analysis of Stem Cells and Differentiation;480
14.15.1;INTRODUCTION;480
14.15.2;KEY WORDS;487
14.15.3;FURTHER READING;488
14.16;Chapter 52. Zebrafish and Stem Cell Research;490
14.16.1;INTRODUCTION;490
14.16.2;THE ZEBRAFISH SYSTEM;490
14.16.3;GENETIC SCREENS IN ZEBRAFISH;492
14.16.4;ZEBRAFISH BLOOD MUTANTS;493
14.16.5;CELL SORTING AND TRANSPLANTATION;494
14.16.6;DISEASE MODELS IN ZEBRAFISH;495
14.16.7;THE FUTURE OF THE SYSTEM;495
14.16.8;ACKNOWLEDGMENTS;496
14.16.9;KEY WORDS;496
14.16.10;FURTHER READING;496
15;Part V: Applications;498
15.1;Chapter 53. Cancer Stem Cells;500
15.1.1;INTRODUCTION;500
15.1.2;CLONALITY AND HETEROGENEITY IN TUMORS;500
15.1.3;THE CANCER STEM CELL MODEL;501
15.1.4;DEFINING FEATURES OF STEM CELLS IN NORMAL TISSUES;502
15.1.5;NOT ALL CANCER CELLS ARE TUMORIGENIC: CLINICAL AND EXPERIMENTAL EVIDENCE;503
15.1.6;SOME CANCERS CAN DIFFERENTIATE INTO NONMALIGNANT CELLS;504
15.1.7;EVIDENCE SUPPORTING THE CANCER STEM CELL MODEL: PROSPECTIVE ISOLATION OF CANCER STEM CELLS;504
15.1.8;ORIGINS OF CANCER STEM CELLS: THE PLASTICITY OF SELF-RENEWAL;507
15.1.9;SIGNALING PATHWAYS IN CANCER STEM CELLS;508
15.1.10;CLINICAL IMPLICATIONS OF CANCER STEM CELLS;509
15.1.11;FUTURE DIRECTIONS;510
15.1.12;FURTHER READING;510
15.2;Chapter 54. Neural Stem Cells for Central Nervous System Repair;516
15.2.1;INTRODUCTION;516
15.2.2;THERAPEUTIC POTENTIAL OF NEURAL STEM CELLS;516
15.2.3;GENE THERAPY USING NEURAL STEM CELLS;520
15.2.4;CELL REPLACEMENT USING NEURAL STEM CELLS;521
15.2.5;"GLOBAL" CELL REPLACEMENT USING NEURAL STEM CELLS;521
15.2.6;NEURAL STEM CELLS DISPLAY AN INHERENT MECHANISM FOR RESCUING DYSFUNCTIONAL NEURONS;523
15.2.7;NEURAL STEM CELLS AS THE GLUE THAT HOLDS MULTIPLE THERAPIES TOGETHER;525
15.2.8;SUMMARY;525
15.2.9;KEY WORDS;527
15.2.10;FURTHER READING;527
15.3;Chapter 55. Spinal Cord Injury;528
15.3.1;INTRODUCTION;528
15.3.2;PROBLEM;528
15.3.3;SPINAL CORD ORGANIZATION;528
15.3.4;INJURY;528
15.3.5;SPONTANEOUS REGENERATION;529
15.3.6;LIMITATIONS AND APPROACHES TO REPAIR AND REDEFINING GOALS;529
15.3.7;SPINAL CORD DEVELOPMENT;530
15.3.8;EMBRYONIC STEM CELLS;531
15.3.9;EMBRYONIC STEM CELLS AND THE NEURAL LINEAGE;531
15.3.10;EMBRONIC STEM CELL TRANSPLANTATION;531
15.3.11;NOVEL APPROACHES TO CENTRAL NERVOUS SYSTEM REPAIR;536
15.3.12;TOWARD HUMAN TRIALS;537
15.3.13;SUMMARY;537
15.3.14;KEY WORDS;537
15.3.15;FURTHER READING;537
15.4;Chapter 56. Use of Embryonic Stem Cells to Treat Heart Disease;538
15.4.1;INTRODUCTION;538
15.4.2;CARDIOMYOCYTE TRANSPLANTATION AS A PARADIGM FOR THE TREATMENT OF DISEASED HEARTS;538
15.4.3;EMBRYONIC STEM CELL-DERIVED CARDIOMYOCYTES, AND FACTORS WHICH ENHANCE CARDIOMYOGENIC DIFFERENTIATION;539
15.4.4;TRANSPLANTATION OF EMBRYONIC STEM CELL-DERIVED CARDIOMYOCYTES IN PRECLINICAL STUDIES, AND CHALLENGES FOR THEIR CLINICAL IMPLEMENTATION;540
15.4.5;SUMMARY;543
15.4.6;ACKNOWLEDGMENTS;543
15.4.7;KEY WORDS;543
15.4.8;FURTHER READING;543
15.5;Chapter 57. Insulin-producing Cells Derived from Stem Cells: A Potential Treatment for Diabetes;544
15.5.1;THE NEED FOR INSULIN-PRODUCING CELLS;544
15.5.2;DEFINING ß-CELLS, STEM CELLS, AND PROGENITOR CELLS;544
15.5.3;THE POTENTIAL OF EMBRYONIC STEM CELLS AS A SOURCE OF INSULIN-PRODUCING CELLS;545
15.5.4;THE POTENTIAL OF ADULT STEM/PROGENITOR CELLS AS A SOURCE OF INSULIN-PRODUCING CELLS;547
15.5.5;TRANSDIFFERENTIATION OF NON-ISLET CELLS TO ISLET CELLS;550
15.5.6;CONCLUSION ON ADULT SOURCES OF NEW ISLET CELLS;551
15.5.7;ACKNOWLEDGMENTS;551
15.5.8;KEY WORDS;551
15.5.9;FURTHER READING;552
15.6;Chapter 58. Burns and Skin Ulcers;554
15.6.1;INTRODUCTION;554
15.6.2;BURNS AND SKIN ULCERS: THE PROBLEM;554
15.6.3;EPIDERMAL STEM CELLS;554
15.6.4;STEM CELLS IN BURNS AND SKIN ULCERS: CURRENT USE;555
15.6.5;FUTURE DEVELOPMENTS;557
15.6.6;SUMMARY;558
15.6.7;ACKNOWLEDGMENTS;559
15.6.8;KEY WORDS;559
15.6.9;FURTHER READING;559
15.7;Chapter 59. Stem Cells and Heart Disease;560
15.7.1;THE HEART IS A SELF-RENEWING ORGAN;560
15.7.2;THE HUMAN HEART CONTAINS A POOL OF RESIDENT CARDIAC PROGENITOR CELLS;561
15.7.3;ANATOMICAL DISTRIBUTION OF CARDIAC PROGENITOR CELLS;565
15.7.4;REPAIR OF MYOCARDIAL DAMAGE BY NON-RESIDENT PROGENITOR CELLS;566
15.7.5;REPAIR OF MYOCARDIAL DAMAGE BY RESIDENT PROGENITOR CELLS;568
15.7.6;MYOCARDIAL REGENERATION IN HUMANS;572
15.7.7;KEY WORDS;573
15.7.8;FURTHER READING;573
15.8;Chapter 60. Stem Cells for the Treatment of Muscular Dystropy: Therapeutic Perspectives;574
15.8.1;INTRODUCTION;574
15.8.2;MYOBLAST TRANSPLANTATION: REASONS FOR FAILURE AND NEW PERSPECTIVES;575
15.8.3;MYOGENIC STEM CELLS IN THE BONE MARROW AND BONE MARROW TRANSPLANTATION;575
15.8.4;CELLULAR ENVIRONMENT OF A DYSTROPHIC MUSCLE: RESIDENT AND MIGRATORY CELLS;578
15.8.5;FUTURE PERSPECTIVES;579
15.8.6;ACKNOWLEDGMENTS;579
15.8.7;KEY WORDS;579
15.8.8;FURTHER READING;580
15.9;Chapter 61. Regeneration of Epidermis from Adult Keratinocyte Stem Cells;582
15.9.1;INTRODUCTION;582
15.9.2;FUTURE DEVELOPMENT;590
15.9.3;SUMMARY;590
15.9.4;ACKNOWLEDGMENTS;590
15.9.5;KEY WORDS;590
15.9.6;FURTHER READING;591
15.10;Chapter 62. Orthopedic Applications of Stem Cells;592
15.10.1;INTRODUCTION;592
15.10.2;BONE;593
15.10.3;CARTILAGE;594
15.10.4;MENISCUS;596
15.10.5;LIGAMENTS AND TENDONS;597
15.10.6;SPINE;599
15.10.7;SUMMARY;600
15.10.8;KEY WORDS;600
15.10.9;FURTHER READING;600
15.11;Chapter 63. Embryonic Stem Cells in Tissue Engineering;602
15.11.1;INTRODUCTION;602
15.11.2;TISSUE ENGINEERING PRINCIPLES AND PERSPECTIVES;602
15.11.3;LIMITATIONS AND HURDLES OF USING EMBRYONIC STEM CELLS IN TISSUE ENGINEERING;606
15.11.4;CONCLUSIONS AND FUTURE PERSPECTIVES;608
15.11.5;KEY WORDS;608
15.11.6;FURTHER READING;608
15.12;Chapter 64. Postnatal Stem Cells in Tissue Engineering;614
15.12.1;INTRODUCTION;614
15.12.2;THE RESERVOIRS OF POSTNATAL STEM CELLS;614
15.12.3;CURRENT APPROACHES TO TISSUE ENGINEERING;616
15.12.4;CONCLUSIONS;620
15.12.5;ACKNOWLEDGMENTS;621
15.12.6;KEY WORDS;621
15.12.7;FURTHER READING;621
15.13;Chapter 65. Stem Cell Gene Therapy;622
15.13.1;INTRODUCTION;622
15.13.2;GENE ADDITION;623
15.13.3;GENOME EDITING;624
15.13.4;REQUIREMENTS FOR SUCCESSFUL STEM CELL GENE THERAPY;624
15.13.5;CONCLUSION;627
15.13.6;KEY WORDS;628
15.13.7;FURTHER READING;628
16;Part VI: Regulation and Ethics;630
16.1;Chapter 66. Ethical Considerations;632
16.1.1;INTRODUCTION;632
16.1.2;IS IT MORALLY PERMISSIBLE TO DESTROY A HUMAN EMBRYO?;632
16.1.3;SHOULD WE POSTPONE HUMAN EMBRYONIC STEM CELL RESEARCH?;633
16.1.4;CAN WE BENEFIT FROM OTHERS' DESTRUCTION OF EMBRYOS?;633
16.1.5;CAN WE CREATE AN EMBRYO TO DESTROY IT?;634
16.1.6;SHOULD WE CLONE HUMAN EMBRYOS?;634
16.1.7;DOES INDUCED PLURIPOTENT STEM CELL RESEARCH ELIMINATE THE ETHICAL QUESTIONS SURROUNDING HUMAN EMBRYONIC STEM CELL RESEARCH?;635
16.1.8;WHAT ETHICAL GUIDELINES SHOULD GOVERN HUMAN EMBRYONIC STEM CELL, THERAPEUTIC CLONING, AND INDUCED PLURIPOTENT STEM CELL RESEARCH?;636
16.1.9;SUMMARY;637
16.1.10;KEY WORDS;637
16.1.11;FURTHER READING;638
16.2;Chapter 67. Stem Cell Research: Religious Considerations;640
16.2.1;INTRODUCTION;640
16.2.2;MAPPING THE TERRAIN;640
16.2.3;PARTICULAR TRADITIONS: AN OVERVIEW;642
16.2.4;ROMAN CATHOLIC CONTRIBUTIONS AND THE 14 DAY THEORY;645
16.2.5;KEY WORDS;648
16.2.6;FURTHER READING;648
16.3;Chapter 68. Stem Cell-based Therapies: Food and Drug Administration Product and Pre-Clinical Regulatory Considerations;650
16.3.1;ABSTRACT;650
16.3.2;INTRODUCTION;650
16.3.3;RESOURCES TO DEVELOP RECOMMENDATIONS FOR THE MANUFACTURE AND CHARACTERIZATION OF STEM CELL-BASED PRODUCTS;651
16.3.4;CRITICAL ELEMENTS FOR DEVELOPING A SAFE STEM CELL-BASED PRODUCT;652
16.3.5;GENERAL EXPECTATIONS FOR CONTROL OF THE MANUFACTURING PROCESS;657
16.3.6;PRECLINICAL EVALUATION SUPPORTS SAFETY ASSESSMENT: PROOF-OF-CONCEPT AND TOXICITY TESTING IN ANIMAL MODELS;657
16.3.7;SUMMARY;659
16.3.8;ACKNOWLEDGMENTS;660
16.3.9;KEY WORDS;660
16.3.10;FURTHER READING;660
16.4;Chapter 69. It's Not About Curiosity, It's About Cures: People Help Drive Progress;662
16.4.1;CHOOSING LIFE;662
16.4.2;SIZE OF THE PROMISE;662
16.4.3;PERSONAL PROMISES FUEL PROGRESS;663
16.4.4;HOPE VERSUS HYPE;664
16.4.5;GIVING LIFE;665
16.4.6;FRIENDS IN NEED AND DEED;665
16.4.7;PEOPLE DRIVE PROGRESS;666
16.4.8;BETTER HEALTH FOR ALL;667
17;Index;668
17.1;A;668
17.2;B;668
17.3;C;669
17.4;D;670
17.5;E;670
17.6;F;672
17.7;G;672
17.8;H;673
17.9;I;674
17.10;J;675
17.11;K;675
17.12;L;675
17.13;M;675
17.14;N;676
17.15;O;677
17.16;P;677
17.17;Q;679
17.18;R;679
17.19;S;679
17.20;T;681
17.21;U;681
17.22;V;681
17.23;W;681
17.24;X;681
17.25;Y;681
17.26;Z;681
