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<p>Preface to the Professor xvii</p> <p>Preface to the Student xxi</p> <p>Acknowledgments xxiii</p> <p>List of Figures xxv</p> <p>List of Tables xxxvii</p> <p>List of Case Studies xxxix</p> <p>List of Focus Boxes xli</p> <p><b>1 A HISTORY OF STEM CELL RESEARCH 1</b></p> <p>Early Studies 1</p> <p>Hematopoietic Stem Cell Discovery 4</p> <p>Mouse Embryonic Stem Cell Discovery 6</p> <p>Successful Neural Stem Cell Culture 7</p> <p>The Discovery of Cancer Stem Cells 8</p> <p>Human Embryonic Stem Cell Discovery 9</p> <p>Stem Cells And Cloning 11</p> <p>Cord Blood Embryonic?]Like Stem Cells—An Alternative to Es and Adult Stem Cells 14</p> <p>Breakthrough In Spinal Cord Injury Repair 15</p> <p>The Generation of ips Cells 16</p> <p>iPS Cells Derived from Keratinocytes 20</p> <p>iPS Induction Without the Use of Viruses 20</p> <p>Transposon?]Mediated iPS 21</p> <p>Protein?]Based iPS 22</p> <p>The Discovery of Human Amniotic Stem Cells 24</p> <p>Human Embryonic Stem Cells Generated Without Embryo Destruction 25</p> <p>Human Cloning 25</p> <p>Mesenchymal Stem Cell?]Derived Human Knee Cartilage 27</p> <p>The First Clinical Trial Using Human Embryonic Stem Cells 28</p> <p>Mitochondrial DNA: A Barrier To Autologous Cell Therapeutics 29</p> <p>Induced Pluripotency And The Potential To Save Endangered Species 30</p> <p>Chapter Summary 33</p> <p>Key Terms 37</p> <p>Review Questions 39</p> <p>Thought Question 40</p> <p>Suggested Readings 40</p> <p><b>2 FUNDAMENTALS OF STEM CELLS 43</b></p> <p>Basic in Vitro Cell Culture—A Historical Perspective 43</p> <p>Stem Cell Culture—Optimal Conditions and Techniques 48</p> <p>Embryonic Stem Cell Culture 49</p> <p>Hematopoietic Stem Cell Culture 52</p> <p>Notch Regulation of HSC Proliferation 52</p> <p>Other Drivers of HSC Proliferation 53</p> <p>Adipose?]Derived Stem Cell Culture 54</p> <p>The Study of Embryonic Development 56</p> <p>Embryonic Development and the Origin of Stem Cells 56</p> <p>Early Events in Embryogenesis 56</p> <p>Germ Cell Development 61</p> <p>Basic Properties of Stem Cells 63</p> <p>Long?]Term Self?]Renewal 63</p> <p>Different Potency Capabilities 63</p> <p>Totipotency 64</p> <p>Pluripotency 65</p> <p>Multipotency 68</p> <p>Oligopotency 68</p> <p>Unipotency 69</p> <p>Types of Stem Cells 70</p> <p>Embryonic Stem Cells 70</p> <p>Fetal Stem Cells 70</p> <p>Amniotic Stem Cells 71</p> <p>Adult Stem Cells 71</p> <p>Induced Pluripotency (iPS) Cells 71</p> <p>Cancer Stem Cells 71</p> <p>The Potential of Stem Cells in Medicine and Medical Research 71</p> <p>Therapeutics 71</p> <p>Tissue Engineering 71</p> <p>Cell Therapy 73</p> <p>Cell?]Based Drug Screening 75</p> <p>Chapter Summary 77</p> <p>Key Terms 80</p> <p>Review Questions 83</p> <p>Thought Question 84</p> <p>Suggested Readings 85</p> <p><b>3 EMBRYONIC STEM, FETAL, AND AMNIOTIC STEM CELLS 87</b></p> <p>ES Cells 87</p> <p>Basic Properties 87</p> <p>Pluripotency 87</p> <p>Indefinite Replicative Capacity 89</p> <p>Signaling and Transcriptional Control of ES Cell Replication 90</p> <p>Examples of ES Cells 92</p> <p>Mouse ES Cells 92</p> <p>Rat ES Cells 95</p> <p>Nonhuman Primate ES Cells 97</p> <p>Human ES Cells 100</p> <p>EC Cells 103</p> <p>Embryonal Germ Cells 105</p> <p>EG Cell Growth Factor Signaling 105</p> <p>Comparing Embryonically Derived Cells 106</p> <p>Fetal Stem Cells 108</p> <p>Basic Properties 108</p> <p>Amniotic Fluid Stem Cells 108</p> <p>Wharton’s Jelly Stem Cells 109</p> <p>Amniotic Membrane Stem Cells 110</p> <p>Placental Stem Cells 110</p> <p>Chapter Summary 112</p> <p>Key Terms 114</p> <p>Review Questions 115</p> <p>Thought Question 116</p> <p>Suggested Reading 116</p> <p><b>4 ADULT STEM CELLS 118</b></p> <p>Discovery and Origin of ASCs 118</p> <p>Basic Properties of ASCs 118</p> <p>Self?]Renewal 119</p> <p>Multipotency 119</p> <p>Examples of ASCs 120</p> <p>Hematopoietic Stem Cells 122</p> <p>Morphology and Marker Expression 123</p> <p>Sources 123</p> <p>Signaling and Multipotency 123</p> <p>Muscle?]Derived Stem Cells 127</p> <p>Myosatellite Cell Morphology and Marker Expression 129</p> <p>Sources 129</p> <p>Signaling, Transcriptional Control, and Multipotency 129</p> <p>Adipose?]Derived Stem Cells 130</p> <p>Morphology and Marker Expression 130</p> <p>Sources 131</p> <p>Signaling and Multipotency 132</p> <p>Mesenchymal Stem Cells 134</p> <p>Morphology and Marker Expression 134</p> <p>Sources 136</p> <p>Signaling and Multipotency 136</p> <p>Neural Stem Cells 140</p> <p>Morphology and Marker Expression 141</p> <p>Sources and Origins 143</p> <p>Signaling and Multipotency 146</p> <p>Endothelial Stem Cells 150</p> <p>Morphology and Marker Expression 150</p> <p>Sources and Origins 152</p> <p>Signaling and Multipotency 153</p> <p>Chapter Summary 156</p> <p>Key Terms 158</p> <p>Review Questions 161</p> <p>Thought Question 162</p> <p>Suggested Readings 162</p> <p><b>5 NUCLEAR REPROGRAMMING 164</b></p> <p>Examples of Nuclear Reprogramming in Nature 166</p> <p>Cell Fusion 166</p> <p>Cell Fusion for the Generation of Hybridomas 169</p> <p>Mechanisms of Cell Fusion 172</p> <p>Comparison of Cell Fusion Techniques 173</p> <p>Electrofusion 173</p> <p>Pegylation 173</p> <p>Viral Induction 173</p> <p>Mechanism of Nuclear Reprogramming in Cell Fusion 175</p> <p>Somatic Cell Nuclear Transfer 176</p> <p>Method for the Production of SCNT?]Derived Cells 177</p> <p>Somatic Cell Nuclear Transfer for the Creation of Stem Cells 178</p> <p>Basic Properties of SCNT?]Derived Stem Cells 180</p> <p>Examples of SCNT?]Derived Stem Cells 181</p> <p>A Note Regarding Genomic Abnormalities in SCNT?]Derived Clones 182</p> <p>Telomeric Length 182</p> <p>DNA Methylation and Epigenetics 183</p> <p>X?]Chromosome Inactivation 185</p> <p>Induced Pluripotency 185</p> <p>Breakthrough in the Production of iPS Cells 187</p> <p>Methods for the Production of iPS Cells 191</p> <p>Retroviral and Lentiviral Gene Delivery 192</p> <p>Adenoviral Gene Delivery 195</p> <p>Sendai Viral Gene Delivery 196</p> <p>Plasmid?]Based Gene Delivery 196</p> <p>mRNA Delivery 198</p> <p>MicroRNA Induction 199</p> <p>Transposon Delivery 200</p> <p>Direct Protein Delivery 200</p> <p>Basic Properties of iPS Cells 201</p> <p>A General Comparison of iPS Cells and Embryonic Stem Cells 203</p> <p>Examples of Derived iPS Cells 205</p> <p>Mouse Embryonic Fibroblast?]Derived iPS Cells 206</p> <p>Human Adult Skin?]Derived iPS Cells 209</p> <p>Advantages of ips Cells Over Other Cell Types 210</p> <p>Origin and Bioethics 211</p> <p>Patient Specificity 211</p> <p>Broad Lineage Differentiation Potential 211</p> <p>“Unlimited” Supply 211</p> <p>Ease of Generation 212</p> <p>Chapter Summary 212</p> <p>Key Terms 214</p> <p>Review Questions 217</p> <p>Thought Question 218</p> <p>Suggested Readings 218</p> <p><b>6 CANCER STEM CELLS 220</b></p> <p>Background on The Origins of Cancer 220</p> <p>Discovery and Origin of Cancer Stem Cells 221</p> <p>Basic Properties of Cancer Stem Cells 225</p> <p>A Comparison of Cancer Stem Cells and Normal Stem Cells 226</p> <p>Signaling Pathways Involved in Cancer Stem Cell Transformation 228</p> <p>Examples of Cancer Stem Cells 229</p> <p>Breast 229</p> <p>Central Nervous System 229</p> <p>Colon 231</p> <p>Ovary 233</p> <p>Pancreas 233</p> <p>Prostate 234</p> <p>Melanoma 235</p> <p>Multiple Myeloma 237</p> <p>Strategies for Treatment Targeting Cancer Stem Cells 238</p> <p>Melanoma Treatment Targeting Chimeric Antigen Receptor 238</p> <p>Multiple Myeloma Treatment Targeting CD20 239</p> <p>Chapter Summary 240</p> <p>Key Terms 241</p> <p>Review Questions 243</p> <p>Thought Question 244</p> <p>Suggested Readings 244</p> <p><b>7 STEM CELLS AS DRUG DISCOVERY PLATFORMS 245</b></p> <p>Embryonic Stem Cells and Mouse Models of Gene Function 245</p> <p>Stem Cell?]Based Screening Assays 250</p> <p>Stem Cells as Lineage Resources for HTS 250</p> <p>Embryonic Stem Cells as a Resource 251</p> <p>Adult Stem Cells as a Resource 253</p> <p>iPS Cells as a Resource 254</p> <p>Cancer Stem Cell Screens 256</p> <p>Reprogramming Screens 258</p> <p>Analysis of Disease Pathways 261</p> <p>Stem Cells As A Toxicity?]Testing Platform 267</p> <p>Stem Cells as a Resource for Developmental Toxicity Testing 267</p> <p>Stem Cells as a Source for Post?]Natal Environmental Toxicity Testing 268</p> <p>Cardiotoxicity 269</p> <p>Hepatotoxicity 272</p> <p>Chapter Summary 273</p> <p>Key Terms 274</p> <p>Review Questions 276</p> <p>Thought Question 277</p> <p>Suggested Readings 277</p> <p><b>8 THERAPEUTIC APPLICATIONS OF STEM CELLS 279</b></p> <p>History of Stem Cells as Therapeutics 279</p> <p>History of Tissue Engineering 279</p> <p>Disease?]Specific Treatment and Patient Trials 282</p> <p>Stem Cell?]Based Patient Trials: An Overview 282</p> <p>Cardiomyopathy and Cardiovascular Disease (CV) 284</p> <p>Neuropathies and Neurodegenerative Diseases 286</p> <p>Spinal Cord Injury 286</p> <p>Brain Damage 288</p> <p>Parkinson’s Disease 292</p> <p>Autoimmune Disorders 292</p> <p>Corneal Defects 296</p> <p>Hematopoietic Disorders 297</p> <p>Sickle Cell Disease 297</p> <p>Wiskott–Aldrich Syndrome 299</p> <p>Cancer 300</p> <p>Muscular Dystrophy 301</p> <p>Liver Disorders 303</p> <p>Veterinary Applications 306</p> <p>Equine 307</p> <p>Canine 309</p> <p>Osteoarthritis (OA) 309</p> <p>Myocardial Infarction 311</p> <p>Spinal Cord Injury 313</p> <p>Stem Cells as an Emerging Industry 314</p> <p>Seminal Discoveries Driving the Growth of a New Industry 317</p> <p>Regulation and Reimbursement of Stem Cell Commercialization 320</p> <p>A Word about Induced Pluripotency and Commercialization 320</p> <p>Chapter Summary 321</p> <p>Key Terms 324</p> <p>Review Questions 326</p> <p>Thought Question 327</p> <p>Suggested Readings 328</p> <p>About the Author 330</p> <p>Index 331</p>

<p><strong>Rob Burgess</strong>, 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.

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