Atala Foundations of Regenerative Medicine

Clinical and Therapeutic Applications
1. Auflage 2009
ISBN: 978-0-12-378562-6
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 823 Seiten

The interdisciplinary field of regenerative medicine holds the promise of repairing and replacing tissues and organs damaged by disease and of developing therapies for previously untreatable conditions, such as diabetes, heart disease, liver disease, and renal failure. Derived from the fields of tissue engineering, cell and developmental biology, biomaterials science, nanotechnology, physics, chemistry, physiology, molecular biology, biochemistry, bioengineering, and surgery, regenerative medicine is one of the most influential topics of biological research today. Derived from the successful Principles of Regenerative Medicine, this volume brings together the latest information on the advances in technology and medicine and the replacement of tissues and organs damaged by disease. Chapters focus on the fundamental principles of regenerative therapies that have crossover with a broad range of disciplines. From the molecular basis to therapeutic applications, this volume is an essential source for students, researchers, and technicians in tissue engineering, stem cells, nuclear transfer (therapeutic cloning), cell, tissue, and organ transplantation, nanotechnology, bioengineering, and medicine to gain a comprehensive understanding of the nature and prospects for this important field.
Highlights the fundamentals of regenerative medicine to relate to a variety of related science and technology fields Introductory chapter directly addresses why regenerative medicine is important to a variety of researchers by providing practical examples and references to primary literature Includes new discoveries from leading researchers on restoration of diseased tissues and organs

Autoren/Hrsg.

Atala, Anthony

Inhaltsverzeichnis

1;Front Cover;1
2;Foundations of Regenerative Medicine;4
3;Copyright Page;5
4;Contents;8
5;Preface;12
6;List of Contributors;24
7;Part I: Introduction to Regenerative Medicine;30
7.1;Chapter 1. Current and Future Perspectives of Regenerative Medicine;31
7.1.1;REGENERATIVE MEDICINE: CURRENT AND FUTURE PERSPECTIVES;31
7.1.2;CONCLUSIONS;39
7.1.3;REFERENCES;39
7.2;Chapter 2. Fundamentals of Cell-Based Therapies;45
7.2.1;INTRODUCTION;45
7.2.2;RATIONALE FOR CELL-BASED THERAPIES;45
7.2.3;CONCLUSIONS;52
7.2.4;ACKNOWLEDGMENTS;53
7.2.5;REFERENCES;53
7.3;Chapter 3. Stem Cell Research;57
7.3.1;INTRODUCTION;57
7.3.2;STEM CELLS;58
7.3.3;STEM CELL MODULATION IN VITRO;64
7.3.4;REGENERATIVE MEDICINE;67
7.3.5;CONCLUSION;71
7.3.6;ACKNOWLEDGMENTS;71
7.3.7;INTERNET RESOURCES;71
7.3.8;REFERENCES;71
8;Part II: Biologic and Molecular Basis for Regenerative Medicine;78
8.1;Chapter 4. Molecular Organization of Cells;79
8.1.1;INTRODUCTION;79
8.1.2;CELLULAR MECHANISMS OF THE EMT;79
8.1.3;MOLECULAR CONTROL OF THE EMT;82
8.1.4;CONCLUSION;88
8.1.5;REFERENCES;88
8.2;Chapter 5. Cell–ECM Interactions in Repair and Regeneration;95
8.2.1;INTRODUCTION;95
8.2.2;COMPOSITION AND DIVERSITY OF THE ECM;95
8.2.3;RECEPTORS FOR ECM MOLECULES;97
8.2.4;SIGNAL TRANSDUCTION EVENTS DURING CELL–ECM INTERACTIONS;99
8.2.5;CELL–ECM INTERACTIONS DURING HEALING OF SKIN WOUNDS;102
8.2.6;CELL–ECM INTERACTIONS DURING REGENERATION;107
8.2.7;IMPLICATIONS FOR REGENERATIVE MEDICINE;112
8.2.8;REFERENCES;113
8.3;Chapter 6. Developmental Mechanisms of Regeneration;129
8.3.1;INTRODUCTION;129
8.3.2;MECHANISMS OF REGENERATION;130
8.3.3;STRATEGIES OF REGENERATIVE MEDICINE;138
8.3.4;CONCLUSION;146
8.3.5;ACKNOWLEDGMENT;147
8.3.6;REFERENCES;147
8.4;Chapter 7. The Molecular Basis of Pluripotency in Principles of Regenerative Medicine;155
8.4.1;INTRODUCTION TO PLURIPOTENCY;155
8.4.2;EXTRACELLULAR SIGNALING FACTORS AND SIGNAL TRANSDUCTION;156
8.4.3;TRANSCRIPTIONAL NETWORKS;160
8.4.4;EPIGENETIC AND ENVIRONMENTAL REGULATION;160
8.4.5;SUMMARY AND PERSPECTIVES;161
8.4.6;REFERENCES;162
9;Part III: Cells and Tissue Development;166
9.1;Chapter 8. Embryonic Stem Cells: Derivation and Properties;167
9.1.1;INTRODUCTION;167
9.1.2;DERIVATION OF ES CELLS;167
9.1.3;CULTURE OF ES CELLS;169
9.1.4;DEVELOPMENTAL POTENTIAL OF ES CELLS;172
9.1.5;CONCLUSION;174
9.1.6;ACKNOWLEDGMENT;175
9.1.7;REFERENCES;175
9.2;Chapter 9. Stem Cells Derived from Amniotic Fluid and Placenta;183
9.2.1;INTRODUCTION;183
9.2.2;CVS AND AMNIOCENTESIS;183
9.2.3;DIFFERENTIATED CELLS FROM AMNIOTIC FLUID AND PLACENTA;184
9.2.4;MESENCHYMAL CELL FROM PLACENTA AND AMNIOTIC FLUID;184
9.2.5;PLURIPOTENT STEM CELLS FROM PLACENTA AND AMNIOTIC FLUID;187
9.2.6;FUTURE DIRECTION;192
9.2.7;SUMMARY;192
9.2.8;REFERENCES;192
9.3;Chapter 10. Bone Marrow Stem Cells: Properties and Pluripotency;195
9.3.1;INTRODUCTION;195
9.3.2;BONE MARROW STEM CELLs;195
9.3.3;BMSCS AND TISSUE REGENERATION;199
9.3.4;IMPORTANT FACTORS REGULATING BMSC HOMING AND DIFFERENTIATION;202
9.3.5;CLINICAL APPLICATIONS OF BMSCS FOR CARDIAC REGENERATION;205
9.3.6;CONCLUSION;205
9.3.7;REFERENCES;206
9.4;Chapter 11. Mesenchymal Stem Cells;211
9.4.1;INTRODUCTION;211
9.4.2;THE DEFINITION OF MSCs;212
9.4.3;THE STEM CELL NATURE OF MSCs;213
9.4.4;SOURCE OF MSCs AND ISOLATION TECHNIQUES;214
9.4.5;WHICH TISSUES CONTAIN MSCs?;215
9.4.6;SKELETAL TISSUE REGENERATION BY MSCs;215
9.4.7;IMMUNOMODULATORY EFFECTS OF MSCs;221
9.4.8;NONSKELETAL TISSUE REGENERATION BY MSCs;223
9.4.9;CONCLUSIONS;225
9.4.10;REFERENCES;226
9.5;Chapter 12. Islet Cell Therapy and Pancreatic Stem Cells;237
9.5.1;INTRODUCTION;237
9.5.2;BENEFITS OF ß-CELL REPLACEMENT THERAPY;238
9.5.3;CURRENT LIMITATIONS TO ß-CELL REPLACEMENT THERAPY;240
9.5.4;ALTERNATIVE SOURCES OF INSULIN-PRODUCING CELLS: STEM CELLS AND ß-CELL REGENERATION;241
9.5.5;PANCREATIC DEVELOPMENT;242
9.5.6;ISLET NEOGENESIS FROM ES CELLS;243
9.5.7;ISLET NEOGENESIS FROM ADULT STEM CELLS;244
9.5.8;TRANSDIFFERENTIATION;246
9.5.9;WHAT THE FUTURE MAY HOLD;247
9.5.10;ACKNOWLEDGMENTS;248
9.5.11;REFERENCES;248
9.6;Chapter 13. Mechanical Determinants of Tissue Development;257
9.6.1;INTRODUCTION;257
9.6.2;MECHANICAL FORCES EXPERIENCED BY TISSUES;258
9.6.3;THE CELL AS A SIGNAL RECEIVER AND PROCESSOR;260
9.6.4;OVERVIEW OF BIOREACTORS;267
9.6.5;PRACTICAL EXAMPLES OF MECHANICAL DETERMINANTS;268
9.6.6;CONCLUSION;272
9.6.7;REFERENCES;272
9.7;Chapter 14. Morphogenesis and Morphogenetic Proteins;275
9.7.1;INTRODUCTION;275
9.7.2;BMPs;276
9.7.3;STEM CELLS;280
9.7.4;SCAFFOLDS OF BIOMIMETIC BIOMATERIALS;282
9.7.5;CARTILAGE-DERIVED MORPHOGENETIC PROTEINS;283
9.7.6;REGENERATIVE MEDICINE AND SURGERY;283
9.7.7;ACKNOWLEDGMENTS;285
9.7.8;REFERENCES;285
9.8;Chapter 15. Physical Stress as a Factor in Tissue Growth and Remodeling;289
9.8.1;INTRODUCTION;289
9.8.2;STRUCTURAL HIERARCHY AND THE CONTINUUM CONCEPT;290
9.8.3;STRAIN AND STRESS DEFINITIONS;290
9.8.4;TISSUE GROWTH, REPAIR, AND REMODELING;296
9.8.5;MECHANOTRANSDUCTION MECHANISMS;298
9.8.6;IN VITRO MECHANICAL CONDITIONING;302
9.8.7;CONCLUSIONS;307
9.8.8;REFERENCES;307
9.9;Chapter 16. Engineering Cellular Microenvironments;313
9.9.1;INTRODUCTION;313
9.9.2;DEFINING THE CELLULAR MICROENVIRONMENT;314
9.9.3;DEFINING THE ORGANIZATION OF MULTICELLULAR CONSTRUCTS;321
9.9.4;DYNAMICALLY CHANGING THE MICROENVIRONMENT;325
9.9.5;CONCLUSIONS AND FUTURE DIRECTIONS;326
9.9.6;ACKNOWLEDGMENTS;327
9.9.7;REFERENCES;327
9.10;Chapter 17. Applications of Nanotechnology;331
9.10.1;INTRODUCTION;331
9.10.2;NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR CELL-BASED THERAPIES;333
9.10.3;NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR BIOMATERIAL CONTROL;335
9.10.4;CONCLUSION;336
9.10.5;REFERENCES;337
10;Part IV: Biomaterials for Regenerative Medicine;340
10.1;Chapter 18. Design Principles in Biomaterials and Scaffolds;341
10.1.1;INTRODUCTION;341
10.1.2;SELECTION OF BIOMATERIALS;342
10.1.3;BIODEGRADABLE SYNTHETIC POLYMERS;342
10.1.4;DESIGN PRINCIPLES OF BIOLOGICAL SCAFFOLDS;343
10.1.5;SUMMARY AND CONCLUSION;351
10.1.6;REFERENCES;352
10.2;Chapter 19. Naturally Occurring Scaffold Materials;355
10.2.1;INTRODUCTION;355
10.2.2;COLLAGEN;355
10.2.3;CHITOSAN;356
10.2.4;INTACT EXTRACELLULAR MATRIX AS A SCAFFOLD MATERIAL;358
10.2.5;REFERENCES;359
10.3;Chapter 20. Synthetic Polymers;365
10.3.1;INTRODUCTION;365
10.3.2;NON-DEGRADABLE SYNTHETIC POLYMERS;367
10.3.3;BIODEGRADABLE SYNTHETIC POLYMERS FOR REGENERATIVE MEDICINE;374
10.3.4;APPLICATIONS OF SYNTHETIC POLYMERS;386
10.3.5;CONCLUSION/ SUMMARY;387
10.3.6;REFERENCES;387
10.4;Chapter 21. Surface Modification of Biomaterials;397
10.4.1;INTRODUCTION;397
10.4.2;PHYSICOCHEMICAL SURFACE MODIFICATIONS;398
10.4.3;OVERCOATING TECHNOLOGIES;401
10.4.4;BIOLOGICAL MODIFICATION OF SURFACES;403
10.4.5;SURFACE CHEMICAL PATTERNING;405
10.4.6;CONCLUSION AND FUTURE PROSPECTS;405
10.4.7;REFERENCES;406
10.5;Chapter 22. Biocompatibility and Bioresponse to Biomaterials;407
10.5.1;INTRODUCTION;407
10.5.2;INFLAMMATION (INNATE IMMUNITY) AND WOUND HEALING;408
10.5.3;FIBROSIS AND FIBROUS ENCAPSULATION;416
10.5.4;IMMUNOTOXICITY (ACQUIRED IMMUNITY);417
10.5.5;SUMMARY;423
10.5.6;REFERENCES;424
11;Part V: Therapeutic Applications: Cell Therapy;428
11.1;Chapter 23. Islet Cell Transplantation;429
11.1.1;INTRODUCTION;429
11.1.2;CLINICAL ISLET TRANSPLANTATION;433
11.1.3;RISKS TO THE RECIPIENT;435
11.1.4;FUTURE CHALLENGES;436
11.1.5;SUMMARY AND CONCLUSIONS;441
11.1.6;REFERENCES;442
11.2;Chapter 24. Cell-Based Repair for Cardiovascular Regeneration and Neovascularization: What, Why, How, and Where Are We Going in the Next 5–10 Years?;447
11.2.1;INTRODUCTION;447
11.2.2;THE STATE OF CELL THERAPY;448
11.2.3;CELL-BASED REPAIR AS A MEANS OF REGENERATION IN CVD;449
11.2.4;VASCULAR INTEGRITY IS A BALANCING ACT IN WHICH INFLAMMATION IS KEY: INJURY VERSUS REPAIR;450
11.2.5;REPARATIVE POTENTIAL OF CELL THERAPY;455
11.2.6;CLINICAL STUDIES;466
11.2.7;WHAT IS REQUIRED FOR SUCCESSFUL REPAIR IN 2007 AND BEYOND?;469
11.2.8;SUMMARY;474
11.2.9;ACKNOWLEDGMENTS;475
11.2.10;REFERENCES;475
11.3;Chapter 25. Cell Therapies for Bone Regeneration;487
11.3.1;INTRODUCTION;487
11.3.2;CURRENT SOURCES OF OSTEOGENIC CELLS AND CELL ISOLATION TECHNIQUES;491
11.3.3;PRECLINICAL AND CLINICAL RESULTS;495
11.3.4;CONCLUSION: FUTURE DEVELOPMENTS AND CHALLENGES;502
11.3.5;REFERENCES;503
11.4;Chapter 26. Cell-Based Therapies for Musculoskeletal Repair;507
11.4.1;INTRODUCTION;507
11.4.2;BIOLOGY OF CELLS IN MUSCULOSKELETAL TISSUES;507
11.4.3;EMBRYONIC AND ADULT STEM CELLS;509
11.4.4;CELL-BASED THERAPIES AND TISSUE ENGINEERING;515
11.4.5;CONCLUSIONS AND PROSPECTS;524
11.4.6;ACKNOWLEDGMENTS;525
11.4.7;REFERENCES;525
11.5;Chapter 27. Hepatocyte Transplantation;531
11.5.1;INTRODUCTION;531
11.5.2;BACKGROUND STUDIES;533
11.5.3;CLINICAL HEPATOCYTE TRANSPLANTATION;535
11.5.4;HEPATOCYTE TRANSPLANTATION NOVEL USES, CHALLENGES, AND FUTURE DIRECTIONS;540
11.5.5;SUMMARY;541
11.5.6;REFERENCES;542
11.6;Chapter 28. Cell-Based Drug Delivery;547
11.6.1;INTRODUCTION;547
11.6.2;CELLS AND CELL PRODUCTS AS DRUG SOURCES;547
11.6.3;CELL ENCAPSULATION FOR THERAPEUTIC DELIVERY MACHINERY;548
11.6.4;CELL-BASED PROTEIN FACTORY;553
11.6.5;DRUG-LOADED TUMOR CELL SYSTEM;554
11.6.6;SUMMARY;556
11.6.7;REFERENCES;556
12;Part VI: Therapeutic Applications: Tissue Therapy;560
12.1;Chapter 29. Engineering of Large Diameter Vessels;561
12.1.1;INTRODUCTION;561
12.1.2;PREVALENCE AND IMPACT OF VASCULAR DISEASE;561
12.1.3;THE NEED FOR IMPROVED DIALYSIS VASCULAR ACCESS;562
12.1.4;VASCULAR PHYSIOLOGY RELEVANT TO TEBVs;563
12.1.5;TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE LITERATURE;567
12.1.6;TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE PROCESS;568
12.1.7;REFERENCES;578
12.2;Chapter 30. Cardiac Tissue;583
12.2.1;INTRODUCTION: FROM TISSUES TO ORGANS: KEY GOALS AND ISSUES;583
12.2.2;CELL AND GENE THERAPY;584
12.2.3;SCAFFOLD-BASED APPROACHES;587
12.2.4;TISSUE AND ORGAN FUNCTION;591
12.2.5;BIOREACTORS AND CONDITIONING;595
12.2.6;IMPLANTATION OF CARDIAC PATCHES;597
12.2.7;SUMMARY;598
12.2.8;REFERENCES;598
12.3;Chapter 31. Intracorporeal Kidney Support;605
12.3.1;INTRODUCTION;605
12.3.2;BASIC PRINCIPLES OF KIDNEY TISSUE REGENERATION;605
12.3.3;CREATION OF RENAL STRUCTURES IN VIVO;607
12.3.4;REGENERATION OF FUNCTIONAL RENAL TISSUE IN VIVO;608
12.3.5;SUMMARY;610
12.3.6;REFERENCES;610
12.4;Chapter 32. Genitourinary System;613
12.4.1;INTRODUCTION;613
12.4.2;RECONSTITUTION STRATEGIES;613
12.4.3;THE ROLE OF BIOMATERIALS;613
12.4.4;VASCULARIZATION;614
12.4.5;PROGRESS IN TISSUE ENGINEERING OF UROLOGIC STRUCTURES;614
12.4.6;ADDITIONAL APPLICATIONS;619
12.4.7;CONCLUSION;621
12.4.8;ACKNOWLEDGMENTS;622
12.4.9;REFERENCES;622
12.5;Chapter 33. Tissue Engineering of the Reproductive System;625
12.5.1;INTRODUCTION;625
12.5.2;MALE;626
12.5.3;FEMALE;639
12.5.4;REFERENCES;646
12.6;Chapter 34. Phalanges and Small Joints;651
12.6.1;INTRODUCTION;651
12.6.2;BASIC PRINCIPLES OF ENGINEERING PHALANGES AND SMALL JOINTS;652
12.6.3;CREATION OF COMPOSITE TISSUE STRUCTURES;654
12.6.4;SUMMARY AND FUTURE PERSPECTIVES IN CLINICAL TRANSLATION;656
12.6.5;REFERENCES;657
12.7;Chapter 35. Functional Tissue Engineering of Ligament and Tendon Injuries;659
12.7.1;INTRODUCTION;659
12.7.2;NORMAL LIGAMENTS AND TENDONS;660
12.7.3;HEALING OF LIGAMENTS AND TENDONS;664
12.7.4;MCL OF THE KNEE;665
12.7.5;APPLICATION OF FTE;667
12.7.6;SUMMARY AND FUTURE DIRECTIONS;674
12.7.7;ACKNOWLEDGMENT;675
12.7.8;REFERENCES;675
12.8;Chapter 36. Tissue Therapy: Implications of Regenerative Medicine for Skeletal Muscle;685
12.8.1;INTRODUCTION;685
12.8.2;THE NATURAL HEALING PROCESS OF SKELETAL MUSCLE;685
12.8.3;THE ROLE OF INFLAMMATION IN SKELETAL MUSCLE HEALING;688
12.8.4;PROMOTING REGENERATION AFTER SKELETAL MUSCLE INJURY;691
12.8.5;FIBROSIS PREVENTION: ANOTHER APPROACH TO IMPROVING SKELETAL MUSCLE HEALING;693
12.8.6;CONCLUSION;694
12.8.7;REFERENCES;695
12.9;Chapter 37. Peripheral Nerve Regeneration;701
12.9.1;INTRODUCTION;701
12.9.2;ISOTROPIC NERVE GRAFTS FOR REGENERATION;703
12.9.3;ANISOTROPIC NERVE GRAFTS;709
12.9.4;NATURAL NERVE GRAFTS;710
12.9.5;ANIMAL MODELS;711
12.9.6;SUMMARY;712
12.9.7;REFERENCES;712
12.10;Chapter 38. Innovative Regenerative Medicine Approaches to Skin Cell-Based Therapy for Patients with Burn Injuries;717
12.10.1;INTRODUCTION;717
12.10.2;CONVENTIONAL THERAPY AND CURRENT COMMERCIAL PRODUCTS;717
12.10.3;PROBLEMS IN THE FIELD;720
12.10.4;CELL APPLICATION INTO THE WOUND BY SPRAYING;721
12.10.5;PATIENT GROUPS AND SELECTION CRITERIA FOR CLINICAL STUDIES IN THE FIELD OF SKIN CELL-BASED THERAPY DEVELOPMENT IN BURN DISEASE PATIENTS;722
12.10.6;INITIAL OWN CASE REPORTS SHOW THAT THE SPRAY TRANSPLANTATION METHOD WITH IN VITRO EXPANDED KERATINOCYTES YIELDS AN IMPROVED OUTCOME OF DEEP DERMAL BURN INJURIES ON…;724
12.10.7;SKIN PROGENITOR CELLS;726
12.10.8;REGULATORY ISSUES;728
12.10.9;DISCUSSION;733
12.10.10;ACKNOWLEDGMENT;735
12.10.11;REFERENCES;735
13;Part VII: Regulations and Ethics;742
13.1;Chapter 39. Ethical Considerations;743
13.1.1;ARGUMENTS THAT DO NOT WORK;743
13.1.2;ARGUMENTS THAT WORK;747
13.1.3;MORALITY AND THE SCOPE OF FUNDED RESEARCH;751
13.1.4;ETHICAL CONSTRAINTS;751
13.1.5;ACKNOWLEDGMENT;752
13.1.6;REFERENCES;753
13.2;Chapter 40. To Make is to Know: The Ethical Issues in Human Tissue Engineering;755
13.2.1;CASE STUDY;755
13.2.2;ARE THERE REASONS IN PRINCIPLE WHY PERFORMING THE BASIC RESEARCH SHOULD BE IMPERMISSIBLE?;756
13.2.3;DUTY AND HEALING: NATURAL MAKERS IN A BROKEN WORLD;757
13.2.4;TO MAKE IS TO KNOW: NOTES ON AN OLD PROBLEM ABOUT KNOWLEDGE;758
13.2.5;WHAT IS A THING: THE PERILS OF DECONSTRUCTION?;759
13.2.6;WHAT CONTEXTUAL FACTORS SURROUNDING THE TECHNOLOGY HAVE TO BE TAKEN INTO ACCOUNT AND DO ANY OF THESE PREVENT THE DEVELOPMENT AND USE OF THE TECHNOLOGY?;759
13.2.7;WHAT PURPOSES, TECHNIQUES, OR APPLICATIONS WOULD BE PERMISSIBLE AND UNDER WHAT CIRCUMSTANCES?;760
13.2.8;WHAT PROCEDURES, STRUCTURES, INVOLVING WHAT POLICIES, SHOULD BE USED TO DECIDE ON APPROPRIATE TECHNIQUES AND USES?;761
13.2.9;CONCLUSION;762
13.3;Chapter 41. Overview of FDA Regulatory Process;763
13.3.1;INTRODUCTION AND CHAPTER OVERVIEW;763
13.3.2;BRIEF LEGISLATIVE HISTORY OF FDA;763
13.3.3;LAWS, REGULATIONS, AND GUIDANCE;764
13.3.4;FDA ORGANIZATION AND JURISDICTIONAL ISSUES;766
13.3.5;APPROVAL MECHANISMS AND CLINICAL STUDIES;767
13.3.6;MEETINGS WITH INDUSTRY, PROFESSIONAL GROUPS, AND SPONSORS;768
13.3.7;REGULATIONS AND GUIDANCE OF SPECIAL INTEREST FOR REGENERATIVE MEDICINE;769
13.3.8;ADVISORY COMMITTEE MEETINGS;776
13.3.9;FDA AND CRITICAL PATH SCIENCE;777
13.3.10;CONCLUSION;778
13.3.11;REFERENCES;778
13.4;Chapter 42. Current Issues in US Patent Law;783
13.4.1;WHAT ARE INTELLECTUAL PROPERTY RIGHTS?;783
13.4.2;WHY ARE INTELLECTUAL PROPERTY RIGHTS IMPORTANT?;793
13.4.3;HOW DO YOU VALUE INTELLECTUAL PROPERTY?;795
14;Index;799
14.1;A;799
14.2;B;800
14.3;C;802
14.4;D;805
14.5;E;806
14.6;F;807
14.7;G;808
14.8;H;808
14.9;I;809
14.10;J;811
14.11;K;811
14.12;L;811
14.13;M;812
14.14;N;814
14.15;O;815
14.16;P;816
14.17;Q;818
14.18;R;818
14.19;S;818
14.20;T;821
14.21;U;822
14.22;V;823
14.23;W;823
14.24;X;823
14.25;Z;823