Mark d'Inverno and Neil Theise and Jane ProphetIngo Roeder and Joerg Galle and Markus LoefflerJames L. SherleyHideyuki Okano and Jun Kohyama and Hiroyuki Ohba and Masanori Sakaguchi and Akinori Tokunaga and Takuya Shimazaki and Hirotaka James OkanoGilbert H. Smith and Robert B. ClarkeMelissa H. Wong and Adnan Z. RizviRichard P. Redvers and Pritinder KaurRebecca J. MorrisEva Schmelzer and Randall E. McClelland and Aloa Melhem and Lili Zhang and Hsin-lei Yao and Eliane Wauthier and William S. Turner and Mark E. Furth and David Gerber and Sanjeev Gupta and Lola M. ReidE. Georg LuebeckStuart A. C. McDonald and Trevor Graham and Christopher S. Potten and Nicholas A. Wright and Ian P. M. Tomlinson and Andrew G. RenehanReaz Vawda and Nigel L. Kennea and Huseyin MehmetIlaria Bellantuono and Leslie J. FairbairnJoanne Ewing and Yvonne Summers

Preface	p. v
Contributors	p. xi
1 Mathematical Modeling of Stem Cells: A Complexity Primer for the Stem-Cell Biologist	p. 1
Introduction	p. 1
Emergence	p. 5
Complex Adaptive Systems with Multiple Interacting Agents	p. 7
Modeling Stem Cells and Cell Lineages as Complex Adaptive Systems	p. 8
Ramifications for Current Thinking	p. 13
Conclusion	p. 13
References	p. 14
2 Theoretical Concepts of Tissue Stem-Cell Organization	p. 17
Introduction	p. 17
Defining Tissue Stem Cells	p. 18
Conceptual Challenges in Tissue Stem-Cell Biology	p. 18
Predictive Theories and Quantitative Models	p. 19
A New Perspective on Stem-Cell Systems	p. 20
Modeling of the Dynamics of Clonal Competition in Hematopoietic Stem Cells	p. 22
Spatio-Temporal Stem-Cell Organization	p. 26
Conceptual Novelty and Achievements	p. 29
References	p. 32
3 Mechanisms of Genetic Fidelity in Mammalian Adult Stem Cells	p. 37
Evolution of Mechanisms of Mammalian Tissue Cell Genetic Fidelity: The Needs of a Few	p. 37
An Exact Definition for the Long-Lived Nature of ASCs	p. 39
Mutagenesis Mechanisms in ASCs	p. 40
Immortal DNA Strand Co-Segregation and a Carpenter's Rule for Genetic Fidelity in ASCs	p. 41
Implications of the Carpenter's Rule for ASC Aging, Cell Kinetics, and DNA Repair Functions	p. 43
Estimation of the Mutation-Avoidance Effect of an Immortal DNA Strand Mechanism in ASCs	p. 45
Evidence for Immortal DNA Strand Co-Segregation in ASCs	p. 47
References	p. 52
4 Neural Stem Cells: Isolation and Self-Renewal	p. 55
Introduction	p. 55
In Vivo Localization of NSCs	p. 55
Control of the Self-Renewal and Differentiation of NSCs	p. 60
Conclusion and Perspectives	p. 66
References	p. 66
5 Stem Cells in Mammary Epithelium	p. 71
Introduction	p. 71
Aging and Reproductive Senescence	p. 72
In Vitro Studies	p. 72
Mammary Stem-Cell Markers	p. 76
Mammary Stem Cells in Carcinogenesis	p. 82
Pregnancy and Breast Cancer Risk	p. 84
Future Prospects	p. 84
References	p. 85
6 Lineage Tracking, Regulation, and Behaviors of Intestinal Stem Cells	p. 89
Introduction	p. 89
Intestinal Epithelium	p. 89
Lineage Tracking as an Approach to Understanding the Stem-Cell Behavior	p. 96
Tracking Stem-Cell Fate Through Understanding What Regulates Their Proliferation and Differentiation	p. 101
Identifying Markers for Intestinal Stem Cells	p. 109
Conclusion	p. 111
References	p. 111
7 Stem Cell Populations in Skin	p. 117
Introduction	p. 117
Conclusion	p. 135
References	p. 135
8 A Perspective on In Vitro Clonogenic Keratinocytes: A Window into the Regulation of the Progenitor Cell Compartment of the Cutaneous Epithelium	p. 149
Introduction	p. 149
Cutaneous Epithelium as a Continually Renewing Tissue Containing In Vitro Clonogenic Keratinocytes	p. 149
Functional Evidence of Stem Cells in Epidermis and Hair Follicles	p. 150
In Mice, Keratinocyte Colony Number is Genetically Defined and Quantitatively Complex	p. 157
Keratinocyte Colony Size is Also Genetically Defined	p. 158
Summary	p. 159
References	p. 159
9 Hepatic Stem Cells and the Liver's Maturational Lineages: Implications for Liver Biology, Gene Expression, and Cell Therapies	p. 161
The Liver as a Maturational Lineage System	p. 161
General Comments on Stem Cells	p. 168
Hepatic Stem Cells	p. 169
Gene Expression	p. 183
Reconstitution of Liver by Cell Transplantation	p. 188
Liver Cell Therapies-Clinical Programs	p. 193
Conclusion	p. 198
References	p. 199
10 Multistage Carcinogenesis: From Intestinal Stem Cell to Colon Cancer in the Population	p. 215
Introduction	p. 215
A Biologically Based Multistage Model for Colon Cancer	p. 217
Adenomatous Polyps-Observations and Model Predictions	p. 221
Summary	p. 225
References	p. 226
11 Intestinal Stem Cells and the Development of Colorectal Neoplasia	p. 229
Introduction	p. 229
Basic Structure and Function of the Intestinal Crypt	p. 230
Stem-Cell Hierarchy	p. 234
Crypt Clonality	p. 236
Intestinal Stem-Cell Repertoire	p. 238
The Concept of Stemness and "Immortal" DNA Strands	p. 239
Molecular Regulation of Normal Intestinal Crypt Homeostasis	p. 242
Early Molecular Events in Colorectal Tumorigenesis	p. 250
Intestinal Stem Cells and the Origin of Colorectal Cancer	p. 252
Colorectal Tumor Morphogenesis	p. 253
Clinical Implications and Future Directions	p. 256
Summary	p. 258
References	p. 259
12 Stem Cells in Neurodegeneration and Injury	p. 271
Introduction	p. 271
Stem Cells	p. 272
The Use of Stem Cells in Brain Disease and Injury	p. 285
Future Perspectives	p. 293
References	p. 293
13 Adult Stem Cells and Gene Therapy	p. 305
Introduction	p. 305
Adult Stem Cells for Gene Therapy	p. 306
Gene Delivery	p. 310
Hurdles to Stem-Cell Gene Therapy	p. 315
Conclusion	p. 321
References	p. 322
14 Clinical Applications of Hematopoietic Stem Cells	p. 339
Introduction	p. 339
Clinical Use of HSCs in Transplantation	p. 339
Autologous Stem-Cell Transplantation	p. 341
ASCT: Malignant Diseases	p. 343
ASCT: Nonmalignant Diseases	p. 351
Allogeneic Stem-Cell Transplantation	p. 353
Specific Clinical Indications for Allogeneic Transplant	p. 357
Cord Blood Transplantation	p. 363
Conclusion	p. 372
References	p. 373
Index	p. 389