Appasani Stem Cells & Regenerative Medicine

From Molecular Embryology to Tissue Engineering
1. Auflage 2010
ISBN: 978-1-60761-860-7
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 629 Seiten

Reihe: Stem Cell Biology and Regenerative Medicine

Defined as, 'The science about the development of an embryo from the fertilization of the ovum to the fetus stage,' embryology has been a mainstay at universities throughout the world for many years. Throughout the last century, embryology became overshadowed by experimental-based genetics and cell biology, transforming the field into developmental biology, which replaced embryology in Biology departments in many universities. Major contributions in this young century in the fields of molecular biology, biochemistry and genomics were integrated with both embryology and developmental biology to provide an understanding of the molecular portrait of a 'development cell.' That new integrated approach is known as stem-cell biology; it is an understanding of the embryology and development together at the molecular level using engineering, imaging and cell culture principles, and it is at the heart of this seminal book. Stem Cells and Regenerative Medicine: From Molecular Embryology to Tissue Engineering is completely devoted to the basic developmental, cellular and molecular biological aspects of stem cells as well as their clinical applications in tissue engineering and regenerative medicine. It focuses on the basic biology of embryonic and cancer cells plus their key involvement in self-renewal, muscle repair, epigenetic processes, and therapeutic applications. In addition, it covers other key relevant topics such as nuclear reprogramming induced pluripotency and stem cell culture techniques using novel biomaterials. A thorough introduction to stem-cell biology, this reference is aimed at graduate students, post-docs, and professors as well as executives and scientists in biotech and pharmaceutical companies.

Autoren/Hrsg.

Appasani, Krishnarao

Appasani, Raghu K.

Inhaltsverzeichnis

1;Preface;6
2;Foreword;12
3;Contents;14
4;Contributors;18
5;Part I Stem Cell Biology;30
5.1;Introduction to Stem Cells and Regenerative Medicine;31
5.1.1;1 Section 1: Stem Cell Biology;32
5.1.2;2 Section 2: Epigenetic and MicroRNA Regulation in Stem Cells;34
5.1.3;3 Section 3: Stem Cells for Therapeutic Applications;35
5.1.4;4 Section 4: Nuclear Reprogramming and Induced Pluripotent Stem Cells;38
5.1.5;5 Section 5: Tissue Engineering;42
5.1.6;6 Section 6: Regenerative Medicine;44
5.2;Embryonic Stem Cells: Discovery, Development, and Current Trends;47
5.2.1;1 Embryonic Stem Cells;47
5.2.1.1;1.1 History;47
5.2.1.2;1.2 Properties of Mouse Embryonic Stem Cells;49
5.2.1.3;1.3 Self-Renewal of Embryonic Stem Cells;49
5.2.1.4;1.4 Differentiation of Mouse Embryonic Stem Cells;51
5.2.2;2 High-Throughput Functional Assays;54
5.2.2.1;2.1 Large-Scale Differentiation Studies;54
5.2.2.2;2.2 Mouse Embryonic Stem Cell Modification and Expression Systems;55
5.2.2.3;2.3 Large-Scale Gene Transfer;57
5.2.3;3 Transcription Factor Studies;59
5.2.3.1;3.1 Transcription Factor Functional Determination in Murine Embryonic Stem Cells;59
5.2.3.2;3.2 Forward Differentiation of Murine Embryonic Stem Cells by Ectopic Expression of Defined Factors;59
5.2.3.3;3.3 Reverse Differentiation of Murine Embryonic Stem Cells by Ectopic Expression of Defined Factors;61
5.2.4;References;63
5.3;Bmi1 in Self-Renewal and Homeostasis of Pancreas;72
5.3.1;1 Introduction;72
5.3.2;2 Stem Cells in Pancreas;75
5.3.3;3 Bmi1’s Role in Stem Cells and Development;76
5.3.4;4 Bmi1’s Role in Exocrine Pancreas;78
5.3.5;5 Bmi1’s Role in Endocrine Pancreas;82
5.3.6;6 Conclusions;82
5.3.7;References;83
5.4;Cancer Stem Cells in Solid Tumors;85
5.4.1;1 Introduction;85
5.4.2;2 Chemoresistance and Radioresistance and Cancer Stem Cells;86
5.4.3;3 Current Strategies for Isolating Cancer Stem Cells;87
5.4.3.1;3.1 Cell Markers;87
5.4.3.2;3.2 “Side-Population” Cells;88
5.4.3.3;3.3 Sphere Formation;89
5.4.3.4;3.4 Aldehyde Dehydrogenase;89
5.4.4;4 Current Knowledge on Existence of Cancer Stem Cells in Solid Tumors;89
5.4.4.1;4.1 Brain Tumors;89
5.4.4.2;4.2 Breast Cancer;91
5.4.4.3;4.3 Colorectal Cancer;92
5.4.4.4;4.4 Other Organs;93
5.4.5;5 Limitations of the Current Strategies to Isolate Cancer Stem Cells;94
5.4.6;6 Conclusion;96
5.4.7;References;97
5.5;Adipose-Derived Stem Cells and Skeletal Muscle Repair;103
5.5.1;1 Introduction;103
5.5.2;2 Adipose Tissue as a Source of Mesenchymal Stem Cells;104
5.5.3;3 In Vitro Myogenic Potential of Adipose-Derived Stem Cells;105
5.5.3.1;3.1 Autonomous Myogenic Potential;105
5.5.3.2;3.2 Myogenic Potential of Adipose-Derived Stem Cells Cultured with Myoblasts;106
5.5.4;4 In Vivo Myogenic Potential of Adipose-Derived Stem Cells;107
5.5.5;5 Cellular Origin of Myogenic Adipose-Derived Stem Cells;107
5.5.6;6 Genetic Modification of Adipose-Derived Stem Cells;109
5.5.6.1;6.1 In Vitro Differentiation Potential of MyoD-Human Multipotent Adipose-Derived Stem Cells;109
5.5.6.2;6.2 MyoD-Human Multipotent Adipose-Derived Stem Cells Contribute to Muscle Repair In Vivo;110
5.5.7;7 Conclusions;112
5.5.8;References;112
5.6;Regeneration of Sensory Cells of Adult Mammalian Inner Ear;114
5.6.1;1 Introduction;114
5.6.2;2 Stratagems for Regenerating Sensory Cells of Adult Mammalian Inner Ear;115
5.6.2.1;2.1 Advanced Therapy Depends on Better Understanding of the Fate of Inner Ear Sensory Cells;115
5.6.2.2;2.2 Transplantation Therapy;116
5.6.3;3 Perspectives on Future Research;123
5.6.4;References;124
5.7;Stem Cells and Their Use in Skeletal Tissue Repair;127
5.7.1;1 Introduction;127
5.7.2;2 Osteodegenerative Diseases;128
5.7.3;3 Treatment Methods: State of the Art;129
5.7.4;4 Types of Stem Cells;130
5.7.4.1;4.1 Mesenchymal Stem Cells;131
5.7.4.2;4.2 Embryonic Stem Cells;133
5.7.5;5 Stem Cells and Bone Differentiation: Features of Mesenchymal Stem Cells and Embryonic Stem Cells;134
5.7.5.1;5.1 Mesenchymal Stem Cells and Embryonic Stem Cells;134
5.7.6;6 Signals That Steer Differentiation;136
5.7.7;7 Stem Cells and Transplantation Aspects;138
5.7.8;8 Conclusion;142
5.7.9;References;143
6;Part II Epigenetic and microRNARegulation in Stem Cells;149
6.1;Epigenetic Identity in Cancer Stem Cells;150
6.1.1;1 Epigenetic Identity in Cancer Stem Cells;150
6.1.1.1;1.1 Epigenetic Control in Normal Tissue Development and Tumorigenesis;150
6.1.1.2;1.2 Epigenetic Mechanisms Involved in Pluripotency;152
6.1.1.3;1.3 Concluding Remarks;159
6.1.2;References;160
6.2;Function of MicroRNA-145 in Human Embryonic Stem Cell Pluripotency;163
6.2.1;1 Human Embryonic Stem Cell ;163
6.2.1.1;1.1 Self-Renewal and Pluripotency;163
6.2.1.2;1.2 Molecular Delineation of Key Regulators in Human Embryonic Stem Cells;164
6.2.1.3;1.3 Transcription Factors and Reprogramming;165
6.2.2;2 MicroRNAs;165
6.2.2.1;2.1 MicroRNA Expression in Embryonic Stem Cells;166
6.2.2.2;2.2 MicroRNA Processing;166
6.2.3;3 MicroRNA-145: Regulator of Stem Cell Fate;166
6.2.3.1;3.1 Identification of miR-145 as a Temporally Regulated MicroRNA During Human Embryonic Stem Cell Differentiation;166
6.2.3.2;3.2 Defining Targets of miR-145: OCT4, SOX2, and KLF4;167
6.2.3.3;3.4 Effect of miR-145 on Endogenous OCT4, KLF4, and SOX2 in Human Embryonic Stem Cells;169
6.2.3.4;3.5 Induced miR-145 Regulates Human Embryonic Stem Cell Self-Renewal;169
6.2.3.5;3.6 miR-145 Promotes Differentiation of Human Embryonic Stem Cells;171
6.2.3.6;3.7 Necessity of miR-145 During Human Embryonic Stem Cell Differentiation;172
6.2.3.7;3.8 A Novel Feedback Loop of miR-145 and Transcription Factors;172
6.2.3.8;3.9 Connection of miR-145 and Pluripotency Network;172
6.2.4;4 Conclusions;173
6.2.5;References;174
6.3;Mesenchymal Stem Cells for Liver Regeneration;176
6.3.1;1 Introduction;176
6.3.2;2 Bone Marrow as a Source of Hepatic Progenitors;177
6.3.3;3 Mesenchymal Stem Cells;180
6.3.4;4 Hepatogenic Potential of Mesenchymal Stem Cells;181
6.3.5;5 Therapeutic Application of Mesenchymal Stem Cells for Liver Diseases;184
6.3.6;6 Clinical Outcomes of Mesenchymal Stem Cells for the Treatment of Liver Diseases;186
6.3.7;7 Regulatory Signaling Network of Liver Generation;187
6.3.8;8 MicroRNA;189
6.3.8.1;8.1 MicroRNAs in Stem Cells;190
6.3.8.2;8.2 MicroRNAs in Liver Development;191
6.3.9;9 Conclusions;191
6.3.10;References;192
6.4;The Role of Time-Lapse Microscopy in Stem Cell Research and Therapy;201
6.4.1;1 Introduction;201
6.4.2;2 Current Methods in Stem Cell Research;203
6.4.2.1;2.1 Genomics and Proteomics;203
6.4.2.2;2.2 Live-Cell Imaging;203
6.4.2.3;2.3 Light Microscopy;204
6.4.3;3 Applications of Time-Lapse Microscopy;205
6.4.3.1;3.1 Differentiation;205
6.4.3.2;3.2 Asymmetric Division;206
6.4.3.3;3.3 Fate Specification;207
6.4.3.4;3.4 Case Study: Time-Lapse Imaging of Human Embryogenesis;208
6.4.3.5;4 Perspectives on Future Clinical Applications;209
6.4.4;5 Conclusion;210
6.4.5;References;210
7;Part III Stem Cells for Therapeutic Applications;212
7.1;Therapeutic Applications of Mesenchymal Stem/Multipotent Stromal Cells;213
7.1.1;1 Introduction;214
7.1.1.1;1.1 History and Definition;214
7.1.1.2;1.2 Origins, Isolation, and In Vitro Culture;214
7.1.1.3;1.3 Characterization;215
7.1.1.4;1.4 Multipotent Differentiation;219
7.1.2;2 Therapeutic Applications;220
7.1.2.1;2.1 Therapeutic Mechanisms;220
7.1.2.1.1;2.1.1 Tissue Regeneration Through Multilineage Differentiation;220
7.1.2.1.2;2.1.2 Paracrine Factors and Immunomodulatory Effects;221
7.1.2.1.3;2.1.3 Genetically Engineered MSCs;223
7.1.2.2;2.2 Advantages of Using MSC as Therapeutic Cells;223
7.1.2.3;2.3 Delivery Routes;223
7.1.2.4;2.4 Therapeutic Applications;225
7.1.2.5;2.5 Challenges of MSC-Based Therapy and Safety Concerns;225
7.1.3;3 Chemically Engineered MSCs with Homing Receptors: A Novel Approach to Promoting MSC Homing;230
7.1.4;4 Conclusion and Perspectives;231
7.1.5;References;232
7.2;Gastrointestinal Stem Cells;237
7.2.1;1 Introduction;237
7.2.2;2 Gut Stem Cells;238
7.2.2.1;2.1 Identification and Isolation of Esophageal Epithelial Stem Cells;238
7.2.2.2;2.2 Intestinal Stem Cells;238
7.2.3;3 Liver Stem Cell Transplantation;240
7.2.4;4 In Vitro Transdifferentiation of Adult Hepatic Stem Cells into Pancreatic Endocrine Hormone–Producing Cells;241
7.2.5;5 Induced Pluripotent Cells;241
7.2.6;6 Mesenchymal Stem Cells;242
7.2.7;References;242
7.3;Lung Epithelial Stem Cells;244
7.3.1;1 Introduction;245
7.3.2;2 Lung Development and Cellular Turnover;245
7.3.3;3 Tracking Lung Epithelial Stem Cells in Vivo and in Vitro;246
7.3.4;4 Cellular Context in the Lung Epithelium;247
7.3.4.1;4.1 Tracheobronchial Zone;247
7.3.4.2;4.2 Bronchiolar Zone;249
7.3.4.3;4.3 Respiratory Alveolar Zone;250
7.3.5;5 Branching Regulators and Components of the Stem Cell Niche;251
7.3.5.1;5.1 Branching Morphogenesis;251
7.3.5.2;5.2 The Vascular Niche;252
7.3.5.3;5.3 Neuroendocrine Bodies;252
7.3.6;6 Modeling Human Lung Morphogenesis in Vitro;253
7.3.6.1;6.1 Human Lung Epithelial Cell Lines;254
7.3.7;7 Discussion and Future Perspectives;255
7.3.8;References;256
7.4;Placental-Derived Stem Cells: Potential Clinical Applications;259
7.4.1;1 Introduction of Stem Cell Sources;260
7.4.2;2 Development of Amnion Epithelium;262
7.4.3;3 Stem Cell Properties of Amnion Epithelial Cells;263
7.4.4;4 Immunoregulatory Role of the Amnion;265
7.4.5;5 Preclinical Animal Studies;268
7.4.5.1;5.1 Neural Disorders;268
7.4.5.2;5.2 Hepatic Regeneration;269
7.4.5.3;5.3 Pancreatic Tissue Insulin Production;270
7.4.6;6 Amnion Epithelial Cells in Lung Regeneration;270
7.4.7;7 Clinical Application of Amnion Epithelial Cells;272
7.4.8;8 Conclusions;273
7.4.9;References;275
7.5;Bone Marrow Cell Therapy for Acute Myocardial Infarction: A Clinical Trial Review;280
7.5.1;1 Introduction;280
7.5.2;2 Nonrandomized Clinical Trials: Proof-of-Concept and Safety;281
7.5.3;3 Randomized Trials: Time to Address Efficacy;282
7.5.4;4 Randomized Clinical Trials: Mixed Results from Mixed Protocols?;287
7.5.5;5 Safety Issues;288
7.5.6;6 Conclusion;288
7.5.7;References;289
7.6;Stem Cell Transplantation to the Heart;293
7.6.1;1 Introduction;293
7.6.2;2 “Stem Cells” and Candidate Cells for Cardiac Cell Therapy;295
7.6.2.1;2.1 Skeletal Myoblasts;295
7.6.2.2;2.2 Bone Marrow–Derived Stem Cells;296
7.6.2.3;2.3 Adult Mesenchymal Stem Cells;297
7.6.2.4;2.4 Fetal Cardiac Myoblasts/Embryonic Stem Cells;298
7.6.2.5;2.5 Endothelial Progenitor Cells;299
7.6.2.6;2.6 Cardiac Stem/Progenitor Cells;300
7.6.3;3 Preclinical Models and Methods of Delivery;301
7.6.3.1;3.1 Reproducible “Positive” Findings;301
7.6.3.2;3.2 Mechanistic Understanding and Other Limitations;302
7.6.4;4 Early Clinical Targets and Initial Human Clinical Trials;303
7.6.4.1;4.1 Therapy for Acute Myocardial Infarction;303
7.6.4.2;4.2 Therapy for Chronic Angina or Heart Failure;304
7.6.5;5 Future Directions and Conclusions;305
7.6.6;References;306
7.7;Adult Neural Progenitor Cells and Cell Replacement Therapy for Huntington Disease;312
7.7.1;1 Introduction;312
7.7.2;2 Neurogenesis in the Adult Human Huntington Disease Brain;314
7.7.3;3 Neurogenesis in the Excitotoxic Rodent Model of Huntington Disease;315
7.7.4;4 Neurogenesis in Transgenic Models of Huntington Disease;317
7.7.5;5 Mechanism of Neurogenesis in Huntington Disease;318
7.7.6;6 Enhancing Neurogenesis in Huntington Disease;319
7.7.7;7 Concluding Remarks;321
7.7.8;References;322
7.8;Migration of Transplanted Neural Stem Cells in Experimental Models of Neurodegenerative Diseases;328
7.8.1;1 Introduction;329
7.8.2;2 Modes and Mechanics of Migration;329
7.8.3;3 Migration in the Forebrain;330
7.8.3.1;3.1 Embryogenesis;330
7.8.3.2;3.2 Adult Neurogenesis;333
7.8.4;4 Migration of Transplanted Cells in Models of Neurodegenerative Diseases;334
7.8.4.1;4.1 Demyelinating Diseases;335
7.8.4.2;4.2 Stroke;338
7.8.4.3;4.3 Epilepsy;340
7.8.5;5 Conclusions;343
7.8.6;References;343
7.9;Prospects for Neural Stem Cell Therapy of Alzheimer Disease;350
7.9.1;1 Introduction;350
7.9.2;2 The Biology of Alzheimer Disease;351
7.9.3;3 Neural Stem Cells;355
7.9.4;4 Future Directions/Conclusions;357
7.9.5;References;358
8;Part IV Nuclear Reprogramming and InducedPluripotent Stem Cells;362
8.1;Nuclear Transfer Embryonic Stem Cells as a New Tool for Basic Biology;363
8.1.1;1 Introduction;364
8.1.2;2 Animal Cloning;365
8.1.3;3 Nuclear Transfer Embryonic Stem Cells;365
8.1.3.1;3.1 Establishment of Nuclear Transfer Embryonic Stem Cell Lines from Individuals;366
8.1.3.2;3.2 Normality of Nuclear Transfer Embryonic Stem Cells;367
8.1.3.3;3.3 Why Are Nuclear Transfer Embryonic Stem Cells Normal?;368
8.1.4;4 Ethical Issues in Using Nuclear Transfer Embryonic Stem Cells;370
8.1.4.1;4.1 A General Attempt to Avoid Ethical Problems;370
8.1.5;5 Improving the Differentiation Potential of Parthenogenetic Embryonic Stem Cells by Nuclear Transfer;371
8.1.6;6 Establishing Nuclear Transfer Embryonic Stem Cell Lines from Aged Mouse Oocytes That Failed to Fertilize;372
8.1.7;7 Applications of Nuclear Transfer Embryonic Stem Cell Techniques;373
8.1.7.1;7.1 Therapeutic Medicine;373
8.1.7.2;7.2 A New Tool for Basic Biology;374
8.1.7.3;7.3 Producing Offspring from Individual Mice;375
8.1.7.4;7.4 Preserving Unique but Infertile Mutant Mouse Genes;375
8.1.7.5;7.5 The Possibility of Resurrecting an Extinct Animal;376
8.1.8;8 Conclusion;377
8.1.9;References;377
8.2;Pluripotent Stem Cells in Reproductive Medicine: Formation of the Human Germ Line in Vitro;382
8.2.1;1 Introduction;383
8.2.2;2 Genesis of Human Germ Cells;384
8.2.3;3 Nuclear Remodeling and Chromatin Dynamics in Primordial Germ Cells;388
8.2.4;4 Current State of the Art for Generating Primordial Germ Cells from Human Pluripotent Cells;389
8.2.5;5 Is Formation of Haploid Gametes from Human Pluripotent Cells a Reality or a Myth?;394
8.2.6;6 Conclusions;395
8.2.7;References;395
8.3;Prospects for Induced Pluripotent Stem Cell Therapy for Diabetes;398
8.3.1;1 The Impact of Diabetes;398
8.3.2;2 Pathophysiology and Complications of Diabetes;400
8.3.3;3 Stem Cells;400
8.3.3.1;3.1 Induced Pluripotent Stem Cells: Cellular Reprogramming by Defined Factors;402
8.3.3.2;3.2 b Cells from Induced Pluripotent Stem Cells;405
8.3.4;4 Future Directions;406
8.3.5;References;407
8.4;Keratinocyte-Induced Pluripotent Stem Cells: From Hair to Where?;410
8.4.1;1 Embryonic Stem Cells;411
8.4.2;2 Induced Pluripotency: The Savior of All?;411
8.4.3;3 Keratinocyte-Derived Induced Pluripotent Stem Cells;413
8.4.3.1;3.1 Background;413
8.4.3.2;3.2 Generation;413
8.4.3.3;3.3 Characterization;414
8.4.3.4;3.4 Differentiation;416
8.4.3.5;3.5 Properties and Efficiency;416
8.4.3.6;3.6 Hair-Derived Keratinocyte-Derived Induced Pluripotent Stem Cells;418
8.4.4;4 Conclusions;419
8.4.5;Acknowledgments;420
8.4.6;References;420
8.5;Generation and Characterization of Induced Pluripotent Stem Cells from Pig;423
8.5.1;1 Introduction;423
8.5.1.1;1.1 Embryonic Stem Cells;423
8.5.1.2;1.2 Pluripotent Stem Cells from Pig;424
8.5.1.3;1.3 Induced Pluripotent Stem Cells Are Ideal Alternatives to Embryonic Stem Cells;425
8.5.2;2 Technical Aspects Involved in the Generation and Characterization of Induced Pluripotent Stem Cells from Porcine Fibroblasts;426
8.5.2.1;2.1 Lentiviral Preparation and Transduction;426
8.5.3;3 Selection of Reprogrammed Cells and Their Properties;429
8.5.4;4 Transcriptome Profile of Porcine Induced Pluripotent Stem Cells;429
8.5.5;5 Comparison of Porcine Induced Pluripotent Stem Cells Generated in Different Laboratories;431
8.5.6;6 Conclusions and Perspectives;433
8.5.7;References;433
8.6;Induced Pluripotent Stem Cells: On the Road Toward Clinical Applications;436
8.6.1;1 Introduction;436
8.6.2;2 Induced Pluripotent Stem Cells Offer Great Therapeutic Potential;437
8.6.3;3 Induced Pluripotent Stem Cells May Bypass Some of the Ethical Obstacles Presented by Embryonic Stem Cells;437
8.6.4;4 Induced Pluripotent Stem Cell–Derived Cell Types Have Promising Therapeutic Potential;438
8.6.5;5 Induced Pluripotent Stem Cells Offer Good Models for Personalized Medicine;438
8.6.6;6 Characteristics of Induced Pluripotent Stem Cells;439
8.6.6.1;6.1 In Vitro Studies of Induced Pluripotent Stem Cells;439
8.6.7;7 Genetic and Epigenetic Properties of Induced Pluripotent Stem Cells;439
8.6.8;8 In Vivo Functional Studies of Induced Pluripotent Stem Cells;440
8.6.8.1;8.1 The First Step: Teratoma Formation and Chimera Generation;440
8.6.9;9 True Pluripotency: Tetraploid Complementation;440
8.6.10;10 Induced Pluripotent Stem Cells: From Bench to Bedside;442
8.6.11;11 Summary and Prospects;444
8.6.12;References;445
8.7;Direct Reprogramming of Human Neural Stem Cells by the Single Transcription Factor OCT4;448
8.7.1;1 Introduction;448
8.7.2;2 Background;449
8.7.2.1;2.1 Generation of Induced Pluripotent Stem Cells from Human Neural Stem Cells by OCT4 Alone;449
8.7.2.2;2.2 Endogenous Expression of Pluripotency Markers;452
8.7.2.3;2.3 Comparison of the Transcriptional Profiles;453
8.7.3;3 Conclusions;454
8.7.4;References;455
9;Part V Tissue Engineering;457
9.1;Stem Cells and Biomaterials: The Tissue Engineering Approach;458
9.2;Microtechnology for Stem Cell Culture;472
9.2.1;1 Introduction;472
9.2.2;2 Microstructured Substrate and Cell Topology;476
9.2.3;3 Soluble Environment Control;478
9.2.4;4 Electrical Stimulation and Recording;482
9.2.5;5 Overview of Microtechnology;482
9.2.6;References;484
9.3;Using Lab-on-a-Chip Technologies for Stem Cell Biology;490
9.3.1;1 Introduction;490
9.3.2;2 Microfluidic Lab-on-a-Chip Meets Stem Cell Biology;491
9.3.2.1;2.1 Physics of the Microscale;492
9.3.2.2;2.2 Fabrication and Working with Microfluidic Devices;493
9.3.3;3 Lab-on-a-Chip Technology for Investigating Stem Cell Biology;494
9.3.3.1;3.1 Engineering Stem Cell Microenvironment in Microfluidic Devices;494
9.3.4;4 Generation of Soluble Gradients;495
9.3.5;5 Generation of Insoluble Gradients;495
9.3.6;6 Generation of Gaseous Gradients;496
9.3.7;7 Control of Substratum Rigidity;497
9.3.8;8 Three-Dimensional Stem Cell Culture;497
9.3.9;9 Control of Shear Stress;497
9.3.9.1;9.1 High-Throughput Screening of Differentiating and Other Factors in Stem Cells;499
9.3.9.2;9.2 Deducing Signal Transduction Pathways in Microfluidic Devices;499
9.3.9.3;9.3 Control of Spatial Arrangement and Topography of Stem Cells;500
9.3.10;10 Conclusions and Outlook;501
9.3.11;References;503
9.4;The Development of Small Molecules and Growth Supplements to Control the Differentiation of Stem Cells and the Formation of Neural Tissues;506
9.4.1;1 Introduction;507
9.4.2;2 Neural Development in the Mammalian Embryo;507
9.4.3;3 In Vitro Models of Neural Differentiation;508
9.4.4;4 Embryonal Carcinoma Cells as Robust Models of Embryonic Stem Cell Neural Differentiation;509
9.4.5;5 Adult Neural Progenitor Cells;510
9.4.6;6 Induced Pluripotent Stem Cells;510
9.4.7;7 Inclusion of Small Molecules in Protocols for Neural Differentiation in Vitro;511
9.4.8;8 Natural Small Molecules;511
9.4.9;9 Limitations Associated with All-trans-Retinoic Acid Use in Vitro;512
9.4.10;10 Synthetic Small Molecules;513
9.4.11;11 Neural Supplements;516
9.4.12;12 Use of Small Molecules for the Treatment of Neurological Disorders;516
9.4.13;13 Conclusions and Future Perspectives;517
9.4.14;References;518
9.5;Long-Term Propagation of Neural Stem Cells: Focus on Three-Dimensional Culture Systems and Mitogenic Factors;521
9.5.1;1 Introduction;521
9.5.2;2 Neural Stem Cells and Their Differentiation Potential;522
9.5.3;3 Central Nervous Areas Used for Isolation of Neural Precursor Cells;522
9.5.4;4 Three-Dimensional Culture Systems for Propagation of Neural Stem Cells;523
9.5.5;5 Neurospheres;523
9.5.6;6 Neural Tissue-Spheres;524
9.5.7;7 Long-Term Propagation of Neural Stem Cells in Three-Dimensional Culture;526
9.5.8;8 Mitogens Used for Propagation of Neural Stem Cells;526
9.5.9;9 Epidermal Growth Factor and Fibroblast Growth Factor 2;526
9.5.10;10 Fibroblast Growth Factor 2;532
9.5.11;11 Leukemia Inhibitory Factor;532
9.5.12;12 Neurogenesis in Vitro: Regional and Developmental Differences;533
9.5.13;13 Neurogenic Priming During Propagation: Influence of Leukemia Inhibitory Factor;535
9.5.14;14 Conclusion;536
9.5.15;References;537
10;Part VI Regenerative Medicine;545
10.1;Stem Cells and Regenerative Medicine in Urology;546
10.1.1;1 Introduction;546
10.1.2;2 Components of Regenerative Medicine and Techniques for Urologic Applications;547
10.1.2.1;2.1 Biomaterials;547
10.1.2.2;2.2 Native Targeted Progenitor Cells;549
10.1.2.3;2.3 Stem Cells and Other Pluripotent Cell Types;550
10.1.3;3 Regenerative Medicine for Major Urologic Structures;553
10.1.3.1;3.1 Urethra;553
10.1.3.2;3.2 Bladder;555
10.1.3.3;3.3 Kidney;559
10.1.4;4 Conclusions;563
10.1.5;Acknowledgments;563
10.1.6;References;563
10.2;Muscle-Derived Stem Cells: A Model for Stem Cell Therapy in Regenerative Medicine;570
10.2.1;1 Background;571
10.2.2;2 Isolation of Murine Muscle-Derived Stem Cells;571
10.2.3;3 Characteristics and Origin of Muscle-Derived Stem Cells;572
10.2.4;4 Differentiation Capabilities of Muscle-Derived Stem Cells;574
10.2.5;5 Cellular Therapy Using Muscle-Derived Stem Cells;574
10.2.6;6 Gene Delivery Using Muscle-Derived Stem Cells;574
10.2.7;7 Role of Muscle-Derived Stem Cells in Muscle Regeneration;575
10.2.8;8 Role of Muscle-Derived Stem Cells in Bone and Cartilage Regeneration;577
10.2.9;9 Role of Muscle-Derived Stem Cells in Cardiac Muscle Regeneration After Infarction;577
10.2.10;10 Factors That Could Influence Stem Cell Performance;578
10.2.11;11 Translational Clinical Applications Based on Muscle-Derived Stem Cells;579
10.2.12;12 Future Directions;580
10.2.13;13 Conclusion;580
10.2.14;Acknowledgments;581
10.2.15;References;581
10.3;Regenerative Strategies for Cardiac Disease;584
10.3.1;1 Introduction;584
10.3.2;2 Autologous Noncardiac Stem Cells and Progenitor Cells;585
10.3.3;3 Embryonic Stem Cells;587
10.3.4;4 Patient-Derived Induced Pluripotent Stem Cells;588
10.3.5;5 Direct Reprogramming of Other Cell Types to the Cardiac Phenotype;589
10.3.6;6 Expansion of Native Cardiomyocyte, Cardiac Stem Cell, or Cardiac Progenitor Cell Populations;592
10.3.7;7 Conclusion: Standards of Evaluation and Prospects for the Future;593
10.3.8;References;595
10.4;Collecting, Processing, Banking, and Using Cord Blood Stem Cells for Regenerative Medicine;599
10.4.1;1 Introduction;599
10.4.2;2 Collection and Processing of Cord Blood Samples;603
10.4.3;3 Cryopreservation and Banking and Banking of Cord Blood Samples;604
10.4.4;4 Cord Blood Stem Cells and Clinical Applications;605
10.4.5;5 Cardiovascular Disease;605
10.4.6;6 Diabetes;607
10.4.7;7 Neurologic Damage;608
10.4.8;8 Stroke;608
10.4.9;9 Orthopedic Applications;610
10.4.10;10 Epithelial Tissue Applications;611
10.4.11;11 Conclusions;612
10.4.12;References;613
11;Index;619