Stem Cells

Rob Burgess, PhD is Vice President of Global Business Development for RayBiotech, Inc. He is also an Assistant Professor of Molecular and Cell Biology at the University of Texas at Dallas within the School of Natural Sciences. He has co-founded several successful start-up companies (Lexicon Genetics, Inc. and Medical Nanotechnologies); restructured and streamlined research, development and manufacturing efforts at Zyvex Corporation; managed over 35 R&D and manufacturing scientists and engineers at Zyvex Corp; authored several book chapters and one textbook on nanomedicine, and published several papers in major peer-reviewed journals such as Science and Nature. He is an expert in the fields of vertebrae functional genomics, stem cells and nanotechnology, with a specific emphasis on stem cell gene targeting and knockout technologies.

• Preface to the Professor xviiPreface to the Student xxiAcknowledgments xxiiiList of Figures xxvList of Tables xxxviiList of Case Studies xxxixList of Focus Boxes xli1 A HISTORY OF STEM CELL RESEARCH 1Early Studies 1Hematopoietic Stem Cell Discovery 4Mouse Embryonic Stem Cell Discovery 6Successful Neural Stem Cell Culture 7The Discovery of Cancer Stem Cells 8Human Embryonic Stem Cell Discovery 9Stem Cells And Cloning 11Cord Blood Embryonic]Like Stem Cells—An Alternative to Es and Adult Stem Cells 14Breakthrough In Spinal Cord Injury Repair 15The Generation of ips Cells 16iPS Cells Derived from Keratinocytes 20iPS Induction Without the Use of Viruses 20Transposon]Mediated iPS 21Protein]Based iPS 22The Discovery of Human Amniotic Stem Cells 24Human Embryonic Stem Cells Generated Without Embryo Destruction 25Human Cloning 25Mesenchymal Stem Cell]Derived Human Knee Cartilage 27The First Clinical Trial Using Human Embryonic Stem Cells 28Mitochondrial DNA: A Barrier To Autologous Cell Therapeutics 29Induced Pluripotency And The Potential To Save Endangered Species 30Chapter Summary 33Key Terms 37Review Questions 39Thought Question 40Suggested Readings 402 FUNDAMENTALS OF STEM CELLS 43Basic in Vitro Cell Culture—A Historical Perspective 43Stem Cell Culture—Optimal Conditions and Techniques 48Embryonic Stem Cell Culture 49Hematopoietic Stem Cell Culture 52Notch Regulation of HSC Proliferation 52Other Drivers of HSC Proliferation 53Adipose]Derived Stem Cell Culture 54The Study of Embryonic Development 56Embryonic Development and the Origin of Stem Cells 56Early Events in Embryogenesis 56Germ Cell Development 61Basic Properties of Stem Cells 63Long]Term Self]Renewal 63Different Potency Capabilities 63Totipotency 64Pluripotency 65Multipotency 68Oligopotency 68Unipotency 69Types of Stem Cells 70Embryonic Stem Cells 70Fetal Stem Cells 70Amniotic Stem Cells 71Adult Stem Cells 71Induced Pluripotency (iPS) Cells 71Cancer Stem Cells 71The Potential of Stem Cells in Medicine and Medical Research 71Therapeutics 71Tissue Engineering 71Cell Therapy 73Cell]Based Drug Screening 75Chapter Summary 77Key Terms 80Review Questions 83Thought Question 84Suggested Readings 853 EMBRYONIC STEM, FETAL, AND AMNIOTIC STEM CELLS 87ES Cells 87Basic Properties 87Pluripotency 87Indefinite Replicative Capacity 89Signaling and Transcriptional Control of ES Cell Replication 90Examples of ES Cells 92Mouse ES Cells 92Rat ES Cells 95Nonhuman Primate ES Cells 97Human ES Cells 100EC Cells 103Embryonal Germ Cells 105EG Cell Growth Factor Signaling 105Comparing Embryonically Derived Cells 106Fetal Stem Cells 108Basic Properties 108Amniotic Fluid Stem Cells 108Wharton’s Jelly Stem Cells 109Amniotic Membrane Stem Cells 110Placental Stem Cells 110Chapter Summary 112Key Terms 114Review Questions 115Thought Question 116Suggested Reading 1164 ADULT STEM CELLS 118Discovery and Origin of ASCs 118Basic Properties of ASCs 118Self]Renewal 119Multipotency 119Examples of ASCs 120Hematopoietic Stem Cells 122Morphology and Marker Expression 123Sources 123Signaling and Multipotency 123Muscle]Derived Stem Cells 127Myosatellite Cell Morphology and Marker Expression 129Sources 129Signaling, Transcriptional Control, and Multipotency 129Adipose]Derived Stem Cells 130Morphology and Marker Expression 130Sources 131Signaling and Multipotency 132Mesenchymal Stem Cells 134Morphology and Marker Expression 134Sources 136Signaling and Multipotency 136Neural Stem Cells 140Morphology and Marker Expression 141Sources and Origins 143Signaling and Multipotency 146Endothelial Stem Cells 150Morphology and Marker Expression 150Sources and Origins 152Signaling and Multipotency 153Chapter Summary 156Key Terms 158Review Questions 161Thought Question 162Suggested Readings 1625 NUCLEAR REPROGRAMMING 164Examples of Nuclear Reprogramming in Nature 166Cell Fusion 166Cell Fusion for the Generation of Hybridomas 169Mechanisms of Cell Fusion 172Comparison of Cell Fusion Techniques 173Electrofusion 173Pegylation 173Viral Induction 173Mechanism of Nuclear Reprogramming in Cell Fusion 175Somatic Cell Nuclear Transfer 176Method for the Production of SCNT]Derived Cells 177Somatic Cell Nuclear Transfer for the Creation of Stem Cells 178Basic Properties of SCNT]Derived Stem Cells 180Examples of SCNT]Derived Stem Cells 181A Note Regarding Genomic Abnormalities in SCNT]Derived Clones 182Telomeric Length 182DNA Methylation and Epigenetics 183X]Chromosome Inactivation 185Induced Pluripotency 185Breakthrough in the Production of iPS Cells 187Methods for the Production of iPS Cells 191Retroviral and Lentiviral Gene Delivery 192Adenoviral Gene Delivery 195Sendai Viral Gene Delivery 196Plasmid]Based Gene Delivery 196mRNA Delivery 198MicroRNA Induction 199Transposon Delivery 200Direct Protein Delivery 200Basic Properties of iPS Cells 201A General Comparison of iPS Cells and Embryonic Stem Cells 203Examples of Derived iPS Cells 205Mouse Embryonic Fibroblast]Derived iPS Cells 206Human Adult Skin]Derived iPS Cells 209Advantages of ips Cells Over Other Cell Types 210Origin and Bioethics 211Patient Specificity 211Broad Lineage Differentiation Potential 211“Unlimited” Supply 211Ease of Generation 212Chapter Summary 212Key Terms 214Review Questions 217Thought Question 218Suggested Readings 2186 CANCER STEM CELLS 220Background on The Origins of Cancer 220Discovery and Origin of Cancer Stem Cells 221Basic Properties of Cancer Stem Cells 225A Comparison of Cancer Stem Cells and Normal Stem Cells 226Signaling Pathways Involved in Cancer Stem Cell Transformation 228Examples of Cancer Stem Cells 229Breast 229Central Nervous System 229Colon 231Ovary 233Pancreas 233Prostate 234Melanoma 235Multiple Myeloma 237Strategies for Treatment Targeting Cancer Stem Cells 238Melanoma Treatment Targeting Chimeric Antigen Receptor 238Multiple Myeloma Treatment Targeting CD20 239Chapter Summary 240Key Terms 241Review Questions 243Thought Question 244Suggested Readings 2447 STEM CELLS AS DRUG DISCOVERY PLATFORMS 245Embryonic Stem Cells and Mouse Models of Gene Function 245Stem Cell]Based Screening Assays 250Stem Cells as Lineage Resources for HTS 250Embryonic Stem Cells as a Resource 251Adult Stem Cells as a Resource 253iPS Cells as a Resource 254Cancer Stem Cell Screens 256Reprogramming Screens 258Analysis of Disease Pathways 261Stem Cells As A Toxicity]Testing Platform 267Stem Cells as a Resource for Developmental Toxicity Testing 267Stem Cells as a Source for Post]Natal Environmental Toxicity Testing 268Cardiotoxicity 269Hepatotoxicity 272Chapter Summary 273Key Terms 274Review Questions 276Thought Question 277Suggested Readings 2778 THERAPEUTIC APPLICATIONS OF STEM CELLS 279History of Stem Cells as Therapeutics 279History of Tissue Engineering 279Disease]Specific Treatment and Patient Trials 282Stem Cell]Based Patient Trials: An Overview 282Cardiomyopathy and Cardiovascular Disease (CV) 284Neuropathies and Neurodegenerative Diseases 286Spinal Cord Injury 286Brain Damage 288Parkinson’s Disease 292Autoimmune Disorders 292Corneal Defects 296Hematopoietic Disorders 297Sickle Cell Disease 297Wiskott–Aldrich Syndrome 299Cancer 300Muscular Dystrophy 301Liver Disorders 303Veterinary Applications 306Equine 307Canine 309Osteoarthritis (OA) 309Myocardial Infarction 311Spinal Cord Injury 313Stem Cells as an Emerging Industry 314Seminal Discoveries Driving the Growth of a New Industry 317Regulation and Reimbursement of Stem Cell Commercialization 320A Word about Induced Pluripotency and Commercialization 320Chapter Summary 321Key Terms 324Review Questions 326Thought Question 327Suggested Readings 328About the Author 330Index 331