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Stem Cells in Toxicology and Medicine

1. Aufl.

von: Saura C. Sahu
162,99 €
Verlag:	Wiley
Format:	EPUB
Veröffentl.:	13.10.2016
ISBN/EAN:	9781119135432
Sprache:	englisch
Anzahl Seiten:	560

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Beschreibungen

Titelbeschreibung

A comprehensive and authoritative compilation of up-to-date developments in stem cell research and its use in toxicology and medicine <ul> <li>Presented by internationally recognized investigators in this exciting field of scientific research</li> <li>Provides an insight into the current trends and future directions of research in this rapidly developing new field</li> <li>A valuable and excellent source of authoritative and up-to-date information for researchers, toxicologists, drug industry, risk assessors and regulators in academia, industry and government </li> </ul>

Inhaltsverzeichnis

List of Contributors xx Preface xxvi Acknowledgements xxvii PART I 1 1 Introduction 3 Saura C. Sahu References 4 2 Application of Stem Cells and iPS Cells in Toxicology 5 Maria Virginia Caballero, Ramon A. Espinoza‐Lewis, and Manila Candiracci 2.1 Introduction 5 2.2 Significance 6 2.3 Stem Cell (SC) Classification 7 2.4 Stem Cells and Pharmacotoxicological Screenings 8 2.5 Industrial Utilization Showcases Stem Cell Technology as a Research Tool 8 2.6 Multipotent Stem Cells (Adult Stem Cells) Characteristics and Current Uses 9 2.7 Mesenchymal Stem Cells (Adult Stem Cells) 10 2.8 Hematopoietic Stem Cells (Adult Stem Cells) 11 2.9 Cardiotoxicity 12 2.10 Hepatotoxicity 15 2.11 Epigenetic Profile 17 2.12 Use of SC and iPSC in Drug Safety 18 2.13 Conclusions and Future Applications 19 Acknowledgments 19 References 19 3 Stem Cells: A Potential Source for High Throughput Screening in Toxicology 26 Harish K Handral, Gopu Sriram, and Tong Cao 3.1 Introduction 26 3.2 Stem Cells 27 3.3 High Throughput Screening (HTS) 31 3.4 Need for a Stem Cell Approach in High Throughput Toxicity Studies 37 3.5 Role of Stem Cells in High Throughput Screening for Toxicity Prediction 38 3.6 Conclusion 40 Acknowledgement 41 Disclosure Statement 41 Author’s Contribution 41 References 41 4 Human Pluripotent Stem Cells for Toxicological Screening 50 Lili Du and Dunjin Chen 4.1 Introduction 50 4.2 The Biological Characteristics of hPSCs 51 4.3 Screening of Embryotoxic Effects using hPSCs 52 4.4 The Potential of hPSC‐Derived Neural Lineages in Neurotoxicology 55 4.5 The Potential of hPSC ‐Derived Cardiomyocytes in Cardiotoxicity 60 4.6 The Potential of hPSC‐Derived Hepatocytes in Hepatotoxicity 62 4.7 Future Challenges and Perspectives for Embryotoxicity and Developmental Toxicity Studies using hPSCs 65 Acknowledgments 66 References 67 5 Effects of Culture Conditions on Maturation of Stem Cell‐Derived Cardiomyocytes 71 Deborah K. Hansen, Amy L. Inselman, and Xi Yang 5.1 Introduction 71 5.2 Lengthening Culture Time 75 5.3 Substrate Stiffness 76 5.4 Structured Substrates 78 5.5 Conclusions 82 Disclaimer 82 References 83 6 Human Stem Cell‐Derived Cardiomyocyte In Vitro Models for Cardiotoxicity Screening 85 Tracy Walker, Kate Harris, Evie Maifoshie, and Khuram Chaudhary 6.1 Introduction 85 6.2 Overview of hPSC‐Derived Cardiomyocytes 88 6.3 Human PSC‐CM Models for Cardiotoxicity Investigations 90 6.4 Conclusions and Future Direction 112 References 112 7 Disease‐Specific Stem Cell Models for Toxicological Screenings and Drug Development 122 Matthias Jung, Juliane‐Susanne Jung, Jovita Schiller, and Insa S. Schroeder 7.1 Evidence for Stem Cell‐Based Drug Development and Toxicological Screenings in Psychiatric Diseases, Cardiovascular Diseases and Diabetes 122 7.2 Disease‐Specific Stem Cell Models for Drug Development in Psychiatric Disorders 127 7.3 Stem Cell Models for Cardiotoxicity and Cardiovascular Disorders 132 7.4 Stem Cell Models for Toxicological Screenings of EDCs 133 References 135 8 Three‐Dimensional Culture Systems and Humanized Liver Models Using Hepatic Stem Cells for Enhanced Toxicity Assessment 145 Ran‐Ran Zhang, Yun‐Wen Zheng, and Hideki Taniguchi 8.1 Introduction 145 8.2 Hepatic Cell Lines and Primary Human Hepatocytes 146 8.3 Embryonic Stem Cells and Induced Pluripotent Stem‐Cell Derived Hepatocytes 147 8.4 Ex Vivo: Three‐Dimensional and Multiple‐Cell Culture System 148 8.5 In Vivo: Humanized Liver Models 149 8.6 Summary 150 Acknowledgments 150 References 150 9 Utilization of In Vitro Neurotoxicity Models in Pre‐Clinical Toxicity Assessment 155 Karin Staflin, Dinah Misner, and Donna Dambach 9.1 Introduction 155 9.2 Current Models of Drug‐Related Clinical Neuropathies and Effects on Electrophysiological Function 159 9.3 Cell Types that Can Potentially Be Used for In Vitro Neurotoxicity Assessment in Drug Development 162 9.4 Utility of iPSC Derived Neurons in In Vitro Safety Assessment 167 9.5 Summary of Key Points for Consideration in Neurotoxicity Assay Development 170 9.6 Concluding Remarks 172 References 172 10 A Human Stem Cell Model for Creating Placental Syncytiotrophoblast, the Major Cellular Barrier that Limits Fetal Exposure to Xenobiotics 179 R. Michael Roberts, Shinichiro Yabe, Ying Yang, and Toshihiko Ezashi 10.1 Introduction 179 10.2 General Features of Placental Structure 180 10.3 The Human Placenta 180 10.4 Human Placental Cells in Toxicology Research 182 10.5 Placental Trophoblast Derived from hESC 183 10.6 Isolation of Syncytial Areas from BAP‐Treated H1 ESC Colonies 185 10.7 Developmental Regulation of Genes Encoding Proteins Potentially Involved in Metabolism of Xenobiotics 185 10.8 Concluding Remarks 191 Acknowledgments 192 References 192 11 The Effects of Endocrine Disruptors on Mesenchymal Stem Cells 196 Marjorie E. Bateman, Amy L. Strong, John McLachlan, Matthew E. Burow, and Bruce A. Bunnell 11.1 Mesenchymal Stem Cells 196 11.2 Endocrine Disruptors 198 11.3 Pesticides 201 11.4 Alkyl Phenols and Derivatives 206 11.5 Bisphenol A 211 11.6 Polychlorinated Biphenyls 216 11.7 Phthalates 221 11.8 Areas for Future Research 225 11.9 Conclusions 226 Abbreviations 226 References 228 12 Epigenetic Landscape in Embryonic Stem Cells 238 Xiaonan Sun, Nicholas Spellmon, Joshua Holcomb, Wen Xue, Chunying Li, and Zhe Yang 12.1 Introduction 238 12.2 DNA Methylation in ESCs 239 12.3 Histone Methylation in ESCs 240 12.4 Chromatin Remodeling and ESCs Regulation 241 12.5 Concluding Remarks 242 Acknowledgements 243 References 243 PART II 247 13 The Effect of Human Pluripotent Stem Cell Platforms on Preclinical Drug Development 249 Kevin G. Chen 13.1 Introduction 249 13.2 Core Signaling Pathways Underlying hPSC Stemness and Differentiation 250 13.3 Basic Components of In Vitro and Ex Vivo hPSC Platforms 251 13.4 Diverse hPSC Culture Platforms for Drug Discovery 252 13.5 Representative Analyses of hPSC‐Based Drug Discovery 255 13.6 Current Challenges and Future Considerations 257 13.7 Concluding Remarks 260 Acknowledgments 260 References 260 14 Generation and Application of 3D Culture Systems in Human Drug Discovery and Medicine 265 H. Rashidi and D.C. Hay 14.1 Introduction 265 14.2 Traditional Scaffold‐Based Tissue Engineering 266 14.3 Scaffold‐Free 3D Culture Systems 269 14.4 Modular Biofabrication 270 14.5 3D Bioprinting 270 14.6 Tissue Modelling and Regenerative Medicine Applications of Pluripotent Stem Cells 272 14.7 Applications in Drug Discovery and Toxicity 275 14.8 Conclusions 278 References 278 15 Characterization and Therapeutic Uses of Adult Mesenchymal Stem Cells 288 Juliann G. Kiang 15.1 Introduction 288 15.2 MSC Characterization 289 15.3 MSCs and Tissue or Organ Therapy 293 15.4 Conclusions 298 Acknowledgments 298 References 298 16 Stem Cell Therapeutics for Cardiovascular Diseases 303 Yuning Hou, Xiaoqing Guan, Shukkur M. Farooq, Xiaonan Sun, Peijun Wang, Zhe Yang, and Chunying Li 16.1 Introduction 303 16.2 Types of Stem/Progenitor Cell‐Derived Endothelial Cells 304 16.3 EPC and Other Stem/Progenitor Cell Therapy in CVDs 306 16.4 Strategies and Approaches for Enhancing EPC Therapy in CVDs 306 16.5 Concluding Remarks 315 Acknowledgments 316 References 316 17 Stem‐Cell‐Based Therapies for Vascular Regeneration in Peripheral Artery Diseases 324 David M Smadja and Jean‐Sébastien Silvestre 17.1 Sources of Stem Cells for Vascular Regeneration 325 17.2 Canonic Mechanisms Governing Vascular Stem Cells Therapeutic Potential 329 17.3 Stem‐Cell‐Based Therapies in Patients with Peripheral Artery Disease 333 References 337 18 Gene Modified Stem/Progenitor‐Cell Therapy for Ischemic Stroke 347 Yaning Li, Guo‐Yuan Yang, and Yongting Wang 18.1 Introduction 347 18.2 Gene Modified Stem Cells for Ischemic Stroke 348 18.3 Gene Transfer Vectors 354 18.4 Unsolved Issues for Gene‐Modified Stem Cells in Ischemic Stroke 356 18.5 Conclusion 356 Abbreviations 356 Acknowledgments 357 References 357 19 Role of Stem Cells in the Gastrointestinal Tract and in the Development of Cancer 363 Pengyu Huang, Bin Li, and Yun‐Wen Zheng 19.1 Introduction 363 19.2 GI Development and Regeneration 365 19.3 GI Tumorigenesis and Stemness Gene Expression 367 19.4 Toxicants and Other Stress Trigger Epigenetic Changes, Dedifferentiation, and Carcinogenesis 368 19.5 Summary and Perspective 369 Acknowledgments 369 References 370 20 Cancer Stem Cells: Concept, Significance, and Management 375 Haseeb Zubair, Shafquat Azim, Sanjeev K. Srivastava, Arun Bhardwaj, Saravanakumar Marimuthu, Mary C. Patton, Seema Singh, and Ajay P. Singh 20.1 Introduction 375 20.2 Stem Cells and Cancer: Historical Perspective 376 20.3 Cancer Stem Cells 377 20.4 Identification and Isolation of CSCs 382 20.5 Pathological Significance of Cancer Stem Cells 388 20.6 Pathways Regulating Cancer Stem Cells 389 20.7 Therapeutic Strategies Targeting Cancer Stem Cells 394 20.8 Conclusion and Future Directions 399 References 400 21 Stem Cell Signaling in the Heterogeneous Development of Medulloblastoma 414 Joanna Triscott and Sandra E. Dunn 21.1 Brain Tumor Cancer Stem Cells 414 21.2 Medulloblastoma 416 21.3 Hijacking Cerebellar Development 417 21.4 Molecular Classification of MB 420 21.5 Mouse Models and Cell of Origin 424 21.6 Additional Drivers of MB 425 21.7 Repurposing Off‐Patent Drugs 426 21.8 Emerging Therapies for MB 428 21.9 Conclusion 429 Acknowledgments 429 References 429 22 Induced Pluripotent Stem Cell‐Derived Outer-Blood‐Retinal Barrier for Disease Modeling and Drug Discovery 436 Jun Jeon, Nathan Hotaling, and Kapil Bharti 22.1 Introduction 436 22.2 The Outer Blood‐Retinal Barrier 437 22.3 iPSC‐Based Model of the Outer-Blood‐Retinal-Barrier 439 22.4 iPSC Based OBRB Disease Models 442 22.5 Applications of iPSC‐Based Ocular Disease Models for Drug Discovery 448 22.6 Conclusion and Future Directions 451 References 451 23 Important Considerations in the Therapeutic Application of Stem Cells in Bone Healing and Regeneration 458 Hoda Elkhenany, Shawn Bourdo, Alexandru Biris, David Anderson, and Madhu Dhar 23.1 Introduction 458 23.2 Stem Cells, Progenitor Cells, Mesenchymal Stem Cells 459 23.3 Scaffolds 461 23.4 Animal Models in Bone Healing and Regeneration 464 23.5 Conclusions and Future Directions 472 References 472 24 Stem Cells from Human Dental Tissue for Regenerative Medicine 481 Junjun Liu and Shangfeng Liu 24.1 Introduction 481 24.2 Dental Stem Cells 482 24.3 Potential Clinical Applications 488 24.4 Safety 492 24.5 Dental Stem Cell Banking 493 24.6 Conclusions and Perspective 494 References 495 25 Stem Cells in the Skin 502 Hongwei Wang, Zhonglan Su, Shiyu Song, Ting Su, Mengyuan Niu, Yaqi Sun, and Hui Xu 25.1 Introduction 502 25.2 Stem Cells in the Skin 503 25.3 Isolation and the Biological Markers of Skin Stem Cells 506 25.4 Skin Stem Cell Niches 508 25.5 Signaling Control of Stem Cell Differentiation 510 25.6 Stem Cells in Skin Aging 514 25.7 Stem Cells in Skin Cancer 516 25.8 Medical Applications of Skin Stem Cells 518 25.9 Conclusions and Future Directions 520 References 521 Author Index 527 Subject Index 529

Autorenportrait

Dr. Saura C. Sahu Research Chemist, Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration. Dr. Sahu is the US Editor for the Journal of Applied Toxicology and the editor of “Hepatotoxicity” (Wiley, 2007), “Toxicogenomics” (Wiley, 2008), “Nanotoxicity” (Wiley, 2009), and “Handbook of Systems Toxicology” (Wiley, 2011).