Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem cells in drug discovery and therapeutic applications in spinal cord injury, brain damage, neurological and autoimmune disorders, among others.
Written by a leader in the field, Stem Cells: A Short Course appeals to both students and instructors alike, appealing to academic enthusiasm for stem cell research and applications.
Contents
Preface to the Professor Preface to the Student Acknowledgments List of Figures List of Tables List of Case Studies List of Focus Boxes Chapter 1 - A History of Stem Cell Research 32 Early Studies 32 Hematopoietic Stem Cell Discovery 36 Mouse Embryonic Stem Cell Discovery 37 Successful Neural Stem Cell Culture 38 The Discovery of Cancer Stem Cells 40 Human Embryonic Stem Cell Discovery 41 Stem Cells and Cloning 43 Cord Blood Embryonic-Like Stem Cells - An Alternative to ES and Adult Stem Cells 47 Breakthrough in Spinal Cord Injury Repair 48 The Generation of Induced Pluripotency (iPS) Cells 50 iPS Cells Derived from Keratinocytes 54 iPS Induction Without the Use of Viruses 55 Transposon-Mediated Induced Pluripotency 55 Protein-Based Induced Pluripotency 57 The Discovery of Human Amniotic Stem Cells 58 Human Embryonic Stem Cells Generated Without Embryo Destruction 59 Human Cloning 61 Mesenchymal Stem Cell-Derived Human Knee Cartilage 62 The First Clinical Trial Using Human Embryonic Stem Cells 63 Mitochondrial DNA: A Barrier to Autologous Cell Therapeutics 64 Induced Pluripotency and the Potential to Save Endangered Species 65 Chapter Summary 68 Key Terms 72 Review Questions 75 Thought Question 76 Chapter 1 Suggested Readings 76 Books, Compilations and Lectures 76 Cited Research Articles 77 Chapter 2 - Fundamentals of Stem Cells 79 Basic In Vitro Cell Culture - A Historical Perspective 79 Stem Cell Culture - Optimal Conditions and Techniques 85 Embryonic Stem Cell Culture 86 Hematopoietic Stem Cell Culture 90 Notch Regulation of HSC Proliferation 90 Other Drivers of HSC Proliferation 91 Adipose-Derived Stem Cell Culture 92 The Study of Embryonic Development 94 Embryonic Development and the Origin of Stem Cells 94 Early Events in Embryogenesis 95 Germ Cell Development 100 Basic Properties of Stem Cells 103 Long-term Self-Renewal 103 Different Potency Capabilities 104 Totipotency 105 Pluripotency 105 Multipotency 109 Oligopotency 109 Unipotency 110 Types of Stem Cells 111 Embryonic Stem Cells 111 Fetal Stem Cells 112 Amniotic Stem Cells 112 Adult Stem Cells 112 Induced Pluripotency (iPS) Cells 112 Cancer Stem Cells 112 The Potential of Stem Cells in Medicine and Medical Research 112 Therapeutics 112 Tissue Engineering 113 Cell Therapy 114 Cell-Based Drug Screening 116 Chapter Summary 120 Key Terms 124 Review Questions 128 Thought Question 129 Chapter 2 Suggested Readings 129 Chapter 3 - Embryonic Stem (ES), Fetal and Amniotic Stem Cells 131 Embryonic Stem Cells 131 Basic Properties 131 Pluripotency 131 Signaling and Transcriptional Regulation of Pluripotency 131 Pluripotency Marker Expression 132 Indefinite Replicative Capacity 133 Signaling and Transcriptional Control of ES Cell Replication 134 Examples of Embryonic Stem Cells 136 Mouse Embryonic Stem Cells 136 Murine ES Cell Culture Conditions 137 Rat Embryonic Stem Cells 139 Non-Human Primate Embryonic Stem Cells 142 Human Embryonic Stem Cells 145 hES Cell Growth Factor Signaling 145 hES Cell Morphology 146 Embryonal Carcinoma (EC) Cells 148 Embryonal Germ (EG) Cells 150 EG Cell Growth Factor Signaling 151 Comparing Embryonically-Derived Cells 152 Fetal Stem Cells 153 Basic Properties 153 Amniotic Fluid Stem Cells 154 Wharton s Jelly Stem Cells 155 Amniotic Membrane Stem Cells 156 Placental Stem Cells 157 Chapter Summary 159 Key Terms 161 Review Questions 162 Thought Question 163 Chapter 3 Suggested Readings 163 Chapter 4 - Adult Stem Cells 165 Discovery and Origin of Adult Stem Cells 165 Basic Properties of Adult Stem Cells 165 Self-renewal 166 Multipotency 167 Examples of Adult Stem Cells 167 Hematopoietic Stem Cells 170 Morphology and Marker Expression 171 Sources 171 Signaling and Multipotency 172 The HSC "Niche" 173 Signals Controlling HSC Fate 173 Muscle-Derived Stem Cells 177 Myosatellite Cell Morphology and Marker Expression 179 Sources 180 Signaling, Transcriptional Control and Multipotency 180 Adipose-Derived Stem Cells 181 Morphology and Marker Expression 182 Sources 183 Signaling and Multipotency 184 Mesenchymal Stem Cells 186 Morphology and Marker Expression 187 Sources 189 Signaling and Multipotency 190 Osteogenesis 192 Adipogenesis 193 Neural Stem Cells 195 Morphology and Marker Expression 197 Sources and Origins 199 Signaling and Multipotency 203 Expansion 203 Neurogenesis 204 Gliogenesis 205 Endothelial Stem Cells 207 Morphology and Marker Expression 208 Sources and Origins 210 Signaling and Multipotency 212 Combinatorial Regulation of Endothelial Progenitor Cell Behavior 212 Angiogenin and Angiopoietin 214 Cytokines and Chemokines 214 Tumor Effects on EPC Behavior 215 Chapter Summary 216 Key Terms 218 Review Questions 221 Thought Question 222 Chapter 4 Suggested Readings 222 Chapter 5 - Nuclear Reprogramming 224 Examples of Nuclear Reprogramming in Nature 225 Cell Fusion 227 Cell Fusion for the Generation of Hybridomas 230 Mechanisms of Cell Fusion 233 Comparison of Cell Fusion Techniques 234 Electrofusion 235 Pegylation 235 Viral Induction 236 Mechanism of Nuclear Reprogramming in Cell Fusion 237 Somatic Cell Nuclear Transfer 239 Method for the Production of SCNT-Derived Cells 240 Somatic Cell Nuclear Transfer for the Creation of Stem Cells 243 Basic Properties of SCNT-Derived Stem Cells 244 Examples of SCNT-Derived Stem Cells 246 A Note Regarding Genomic Abnormalities in SCNT-Derived Clones 246 Telomeric Length 246 DNA Methylation and Epigenetics 249 X-Chromosome Inactivation 250 Induced Pluripotency 253 Breakthrough in the Production of iPS Cells 253 Methods for the Production of iPS Cells 258 Retroviral and Lentiviral Gene Delivery 259 Adenoviral Gene Delivery 264 Sendai Viral Gene Delivery 264 Plasmid-Based Gene Delivery 265 mRNA Delivery 268 MicroRNA Induction 268 Transposon Delivery 269 Direct Protein Delivery 270 Basic Properties of iPS Cells 271 A General Comparison of iPS Cells and Embryonic Stem Cells 274 Examples of Derived iPS Cells 277 Mouse Embryonic Fibroblast-Derived iPS Cells 277 Human Adult Skin-Derived iPS Cells 281 Advantages of iPS Cells Over Other Cell Types 283 Origin and Bioethics 284 Patient Specificity 284 Broad Lineage Differentiation Potential 284 "Unlimited" Supply 285 Ease of Generation 285 Chapter Summary 286 Key Terms 288 Review Questions 291 Thought Question 292 Chapter 5 Suggested Readings 292 Chapter 6 - Cancer Stem Cells 295 Background on the Origins of Cancer 295 Discovery and Origin of Cancer Stem Cells 296 Basic Properties of Cancer Stem Cells 301 Signaling Pathways Involved in Cancer Stem Cell Transformation 306 Examples of Cancer Stem Cells 307 Breast 307 Central Nervous System 307 Colon 310 Ovary 312 Pancreas 313 Prostate 314 Melanoma 315 Multiple Myeloma 317 Strategies for Treatment Targeting Cancer Stem Cells 318 Melanoma Treatment Targeting CAR 319 Multiple Myeloma Treatment Targeting CD20 320 Chapter Summary 321 Key Terms 323 Review Questions 324 Thought Question 325 Chapter 6 Suggested Readings 325 Chapter 7 - Stem Cells as Drug Discovery Platforms 327 Embryonic Stem Cells and Mouse Models of Gene Function 327 Stem Cell-Based Screening Assays 333 Stem Cells as Lineage Resources for HTS 333 Embryonic Stem Cells as a Resource 334 Adult Stem Cells as a Resource 336 iPS Cells as a Resource 339 Cancer Stem Cell Screens 341 Reprogramming Screens 343 Analysis of Disease Pathways 347 Stem Cells as a Toxicity Testing Platform 355 Stem Cells as a Resource for Developmental Toxicity Testing 355 Stem Cells as a Source for Post-Natal Environmental Toxicity Testing 357 Cardiotoxicity 358 Hepatotoxicity 361 Chapter Summary 363 Key Terms 364 Review Questions 367 Thought Question 368 Chapter 7 Suggested Readings 368 Chapter 8 - - Therapeutic Applications of Stem Cells 370 History of Stem Cells as Therapeutics 370 History of Tissue Engineering 370 Disease-Specific Treatment and Patient Trials 374 Stem Cell-Based Patient Trials: An Overview 374 Cardiomyopathy and Cardiovascular Disease (CV) 376 Neuropathies and Neurodegenerative Diseases 378 Spinal Cord Injury (SCI) 379 Brain Damage 382 Mechanism of Action of Stem Cell Brain Damage Repair 385 Parkinson's Disease 386 Autoimmune Disorders 388 Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS) 388 Juvenile Idiopathic Arthritis 389 Corneal Defects 391 Hematopoietic Disorders 392 Sickle Cell Disease 392 Wiskott-Aldrich Syndrome 395 Cancer 396 Muscular Dystrophy 397 Liver Disorders 401 Veterinary Applications 403 Equine 404 Canine 406 Osteoarthritis (OA) 406 Myocardial Infarction 409 Bone Fractures 410 Spinal Cord Injury 412 Stem Cells as an Emerging Industry 413 Seminal Discoveries Driving the Growth of a New Industry 418 Regulation and Reimbursement of Stem Cell Commercialization 420 A Word about Induced Pluripotency and Commercialization 421 Chapter Summary 423 Key Terms 425 Review Questions 428 Thought Question 429 Chapter 8 Suggested Readings 429 About the Author Index
