Foundations of Regenerative Medicine (eBook)

Front Cover 1
Foundations of Regenerative Medicine 4
Copyright Page 5
Contents 8
Preface 12
List of Contributors 24
Part I: Introduction to Regenerative Medicine 30
Chapter 1. Current and Future Perspectives of Regenerative Medicine 31
REGENERATIVE MEDICINE: CURRENT AND FUTURE PERSPECTIVES 31
CONCLUSIONS 39
REFERENCES 39
Chapter 2. Fundamentals of Cell-Based Therapies 45
INTRODUCTION 45
RATIONALE FOR CELL-BASED THERAPIES 45
CONCLUSIONS 52
ACKNOWLEDGMENTS 53
REFERENCES 53
Chapter 3. Stem Cell Research 57
INTRODUCTION 57
STEM CELLS 58
STEM CELL MODULATION IN VITRO 64
REGENERATIVE MEDICINE 67
CONCLUSION 71
ACKNOWLEDGMENTS 71
INTERNET RESOURCES 71
REFERENCES 71
Part II: Biologic and Molecular Basis for Regenerative Medicine 78
Chapter 4. Molecular Organization of Cells 79
INTRODUCTION 79
CELLULAR MECHANISMS OF THE EMT 79
MOLECULAR CONTROL OF THE EMT 82
CONCLUSION 88
REFERENCES 88
Chapter 5. Cell–ECM Interactions in Repair and Regeneration 95
INTRODUCTION 95
COMPOSITION AND DIVERSITY OF THE ECM 95
RECEPTORS FOR ECM MOLECULES 97
SIGNAL TRANSDUCTION EVENTS DURING CELL–ECM INTERACTIONS 99
CELL–ECM INTERACTIONS DURING HEALING OF SKIN WOUNDS 102
CELL–ECM INTERACTIONS DURING REGENERATION 107
IMPLICATIONS FOR REGENERATIVE MEDICINE 112
REFERENCES 113
Chapter 6. Developmental Mechanisms of Regeneration 129
INTRODUCTION 129
MECHANISMS OF REGENERATION 130
STRATEGIES OF REGENERATIVE MEDICINE 138
CONCLUSION 146
ACKNOWLEDGMENT 147
REFERENCES 147
Chapter 7. The Molecular Basis of Pluripotency in Principles of Regenerative Medicine 155
INTRODUCTION TO PLURIPOTENCY 155
EXTRACELLULAR SIGNALING FACTORS AND SIGNAL TRANSDUCTION 156
TRANSCRIPTIONAL NETWORKS 160
EPIGENETIC AND ENVIRONMENTAL REGULATION 160
SUMMARY AND PERSPECTIVES 161
REFERENCES 162
Part III: Cells and Tissue Development 166
Chapter 8. Embryonic Stem Cells: Derivation and Properties 167
INTRODUCTION 167
DERIVATION OF ES CELLS 167
CULTURE OF ES CELLS 169
DEVELOPMENTAL POTENTIAL OF ES CELLS 172
CONCLUSION 174
ACKNOWLEDGMENT 175
REFERENCES 175
Chapter 9. Stem Cells Derived from Amniotic Fluid and Placenta 183
INTRODUCTION 183
CVS AND AMNIOCENTESIS 183
DIFFERENTIATED CELLS FROM AMNIOTIC FLUID AND PLACENTA 184
MESENCHYMAL CELL FROM PLACENTA AND AMNIOTIC FLUID 184
PLURIPOTENT STEM CELLS FROM PLACENTA AND AMNIOTIC FLUID 187
FUTURE DIRECTION 192
SUMMARY 192
REFERENCES 192
Chapter 10. Bone Marrow Stem Cells: Properties and Pluripotency 195
INTRODUCTION 195
BONE MARROW STEM CELLs 195
BMSCS AND TISSUE REGENERATION 199
IMPORTANT FACTORS REGULATING BMSC HOMING AND DIFFERENTIATION 202
CLINICAL APPLICATIONS OF BMSCS FOR CARDIAC REGENERATION 205
CONCLUSION 205
REFERENCES 206
Chapter 11. Mesenchymal Stem Cells 211
INTRODUCTION 211
THE DEFINITION OF MSCs 212
THE STEM CELL NATURE OF MSCs 213
SOURCE OF MSCs AND ISOLATION TECHNIQUES 214
WHICH TISSUES CONTAIN MSCs? 215
SKELETAL TISSUE REGENERATION BY MSCs 215
IMMUNOMODULATORY EFFECTS OF MSCs 221
NONSKELETAL TISSUE REGENERATION BY MSCs 223
CONCLUSIONS 225
REFERENCES 226
Chapter 12. Islet Cell Therapy and Pancreatic Stem Cells 237
INTRODUCTION 237
BENEFITS OF & #946
CURRENT LIMITATIONS TO & #946
ALTERNATIVE SOURCES OF INSULIN-PRODUCING CELLS: STEM CELLS AND & #946
PANCREATIC DEVELOPMENT 242
ISLET NEOGENESIS FROM ES CELLS 243
ISLET NEOGENESIS FROM ADULT STEM CELLS 244
TRANSDIFFERENTIATION 246
WHAT THE FUTURE MAY HOLD 247
ACKNOWLEDGMENTS 248
REFERENCES 248
Chapter 13. Mechanical Determinants of Tissue Development 257
INTRODUCTION 257
MECHANICAL FORCES EXPERIENCED BY TISSUES 258
THE CELL AS A SIGNAL RECEIVER AND PROCESSOR 260
OVERVIEW OF BIOREACTORS 267
PRACTICAL EXAMPLES OF MECHANICAL DETERMINANTS 268
CONCLUSION 272
REFERENCES 272
Chapter 14. Morphogenesis and Morphogenetic Proteins 275
INTRODUCTION 275
BMPs 276
STEM CELLS 280
SCAFFOLDS OF BIOMIMETIC BIOMATERIALS 282
CARTILAGE-DERIVED MORPHOGENETIC PROTEINS 283
REGENERATIVE MEDICINE AND SURGERY 283
ACKNOWLEDGMENTS 285
REFERENCES 285
Chapter 15. Physical Stress as a Factor in Tissue Growth and Remodeling 289
INTRODUCTION 289
STRUCTURAL HIERARCHY AND THE CONTINUUM CONCEPT 290
STRAIN AND STRESS DEFINITIONS 290
TISSUE GROWTH, REPAIR, AND REMODELING 296
MECHANOTRANSDUCTION MECHANISMS 298
IN VITRO MECHANICAL CONDITIONING 302
CONCLUSIONS 307
REFERENCES 307
Chapter 16. Engineering Cellular Microenvironments 313
INTRODUCTION 313
DEFINING THE CELLULAR MICROENVIRONMENT 314
DEFINING THE ORGANIZATION OF MULTICELLULAR CONSTRUCTS 321
DYNAMICALLY CHANGING THE MICROENVIRONMENT 325
CONCLUSIONS AND FUTURE DIRECTIONS 326
ACKNOWLEDGMENTS 327
REFERENCES 327
Chapter 17. Applications of Nanotechnology 331
INTRODUCTION 331
NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR CELL-BASED THERAPIES 333
NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR BIOMATERIAL CONTROL 335
CONCLUSION 336
REFERENCES 337
Part IV: Biomaterials for Regenerative Medicine 340
Chapter 18. Design Principles in Biomaterials and Scaffolds 341
INTRODUCTION 341
SELECTION OF BIOMATERIALS 342
BIODEGRADABLE SYNTHETIC POLYMERS 342
DESIGN PRINCIPLES OF BIOLOGICAL SCAFFOLDS 343
SUMMARY AND CONCLUSION 351
REFERENCES 352
Chapter 19. Naturally Occurring Scaffold Materials 355
INTRODUCTION 355
COLLAGEN 355
CHITOSAN 356
INTACT EXTRACELLULAR MATRIX AS A SCAFFOLD MATERIAL 358
REFERENCES 359
Chapter 20. Synthetic Polymers 365
INTRODUCTION 365
NON-DEGRADABLE SYNTHETIC POLYMERS 367
BIODEGRADABLE SYNTHETIC POLYMERS FOR REGENERATIVE MEDICINE 374
APPLICATIONS OF SYNTHETIC POLYMERS 386
CONCLUSION/ SUMMARY 387
REFERENCES 387
Chapter 21. Surface Modification of Biomaterials 397
INTRODUCTION 397
PHYSICOCHEMICAL SURFACE MODIFICATIONS 398
OVERCOATING TECHNOLOGIES 401
BIOLOGICAL MODIFICATION OF SURFACES 403
SURFACE CHEMICAL PATTERNING 405
CONCLUSION AND FUTURE PROSPECTS 405
REFERENCES 406
Chapter 22. Biocompatibility and Bioresponse to Biomaterials 407
INTRODUCTION 407
INFLAMMATION (INNATE IMMUNITY) AND WOUND HEALING 408
FIBROSIS AND FIBROUS ENCAPSULATION 416
IMMUNOTOXICITY (ACQUIRED IMMUNITY) 417
SUMMARY 423
REFERENCES 424
Part V: Therapeutic Applications: Cell Therapy 428
Chapter 23. Islet Cell Transplantation 429
INTRODUCTION 429
CLINICAL ISLET TRANSPLANTATION 433
RISKS TO THE RECIPIENT 435
FUTURE CHALLENGES 436
SUMMARY AND CONCLUSIONS 441
REFERENCES 442
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
INTRODUCTION 447
THE STATE OF CELL THERAPY 448
CELL-BASED REPAIR AS A MEANS OF REGENERATION IN CVD 449
VASCULAR INTEGRITY IS A BALANCING ACT IN WHICH INFLAMMATION IS KEY: INJURY VERSUS REPAIR 450
REPARATIVE POTENTIAL OF CELL THERAPY 455
CLINICAL STUDIES 466
WHAT IS REQUIRED FOR SUCCESSFUL REPAIR IN 2007 AND BEYOND? 469
SUMMARY 474
ACKNOWLEDGMENTS 475
REFERENCES 475
Chapter 25. Cell Therapies for Bone Regeneration 487
INTRODUCTION 487
CURRENT SOURCES OF OSTEOGENIC CELLS AND CELL ISOLATION TECHNIQUES 491
PRECLINICAL AND CLINICAL RESULTS 495
CONCLUSION: FUTURE DEVELOPMENTS AND CHALLENGES 502
REFERENCES 503
Chapter 26. Cell-Based Therapies for Musculoskeletal Repair 507
INTRODUCTION 507
BIOLOGY OF CELLS IN MUSCULOSKELETAL TISSUES 507
EMBRYONIC AND ADULT STEM CELLS 509
CELL-BASED THERAPIES AND TISSUE ENGINEERING 515
CONCLUSIONS AND PROSPECTS 524
ACKNOWLEDGMENTS 525
REFERENCES 525
Chapter 27. Hepatocyte Transplantation 531
INTRODUCTION 531
BACKGROUND STUDIES 533
CLINICAL HEPATOCYTE TRANSPLANTATION 535
HEPATOCYTE TRANSPLANTATION NOVEL USES, CHALLENGES, AND FUTURE DIRECTIONS 540
SUMMARY 541
REFERENCES 542
Chapter 28. Cell-Based Drug Delivery 547
INTRODUCTION 547
CELLS AND CELL PRODUCTS AS DRUG SOURCES 547
CELL ENCAPSULATION FOR THERAPEUTIC DELIVERY MACHINERY 548
CELL-BASED PROTEIN FACTORY 553
DRUG-LOADED TUMOR CELL SYSTEM 554
SUMMARY 556
REFERENCES 556
Part VI: Therapeutic Applications: Tissue Therapy 560
Chapter 29. Engineering of Large Diameter Vessels 561
INTRODUCTION 561
PREVALENCE AND IMPACT OF VASCULAR DISEASE 561
THE NEED FOR IMPROVED DIALYSIS VASCULAR ACCESS 562
VASCULAR PHYSIOLOGY RELEVANT TO TEBVs 563
TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE LITERATURE 567
TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE PROCESS 568
REFERENCES 578
Chapter 30. Cardiac Tissue 583
INTRODUCTION: FROM TISSUES TO ORGANS: KEY GOALS AND ISSUES 583
CELL AND GENE THERAPY 584
SCAFFOLD-BASED APPROACHES 587
TISSUE AND ORGAN FUNCTION 591
BIOREACTORS AND CONDITIONING 595
IMPLANTATION OF CARDIAC PATCHES 597
SUMMARY 598
REFERENCES 598
Chapter 31. Intracorporeal Kidney Support 605
INTRODUCTION 605
BASIC PRINCIPLES OF KIDNEY TISSUE REGENERATION 605
CREATION OF RENAL STRUCTURES IN VIVO 607
REGENERATION OF FUNCTIONAL RENAL TISSUE IN VIVO 608
SUMMARY 610
REFERENCES 610
Chapter 32. Genitourinary System 613
INTRODUCTION 613
RECONSTITUTION STRATEGIES 613
THE ROLE OF BIOMATERIALS 613
VASCULARIZATION 614
PROGRESS IN TISSUE ENGINEERING OF UROLOGIC STRUCTURES 614
ADDITIONAL APPLICATIONS 619
CONCLUSION 621
ACKNOWLEDGMENTS 622
REFERENCES 622
Chapter 33. Tissue Engineering of the Reproductive System 625
INTRODUCTION 625
MALE 626
FEMALE 639
REFERENCES 646
Chapter 34. Phalanges and Small Joints 651
INTRODUCTION 651
BASIC PRINCIPLES OF ENGINEERING PHALANGES AND SMALL JOINTS 652
CREATION OF COMPOSITE TISSUE STRUCTURES 654
SUMMARY AND FUTURE PERSPECTIVES IN CLINICAL TRANSLATION 656
REFERENCES 657
Chapter 35. Functional Tissue Engineering of Ligament and Tendon Injuries 659
INTRODUCTION 659
NORMAL LIGAMENTS AND TENDONS 660
HEALING OF LIGAMENTS AND TENDONS 664
MCL OF THE KNEE 665
APPLICATION OF FTE 667
SUMMARY AND FUTURE DIRECTIONS 674
ACKNOWLEDGMENT 675
REFERENCES 675
Chapter 36. Tissue Therapy: Implications of Regenerative Medicine for Skeletal Muscle 685
INTRODUCTION 685
THE NATURAL HEALING PROCESS OF SKELETAL MUSCLE 685
THE ROLE OF INFLAMMATION IN SKELETAL MUSCLE HEALING 688
PROMOTING REGENERATION AFTER SKELETAL MUSCLE INJURY 691
FIBROSIS PREVENTION: ANOTHER APPROACH TO IMPROVING SKELETAL MUSCLE HEALING 693
CONCLUSION 694
REFERENCES 695
Chapter 37. Peripheral Nerve Regeneration 701
INTRODUCTION 701
ISOTROPIC NERVE GRAFTS FOR REGENERATION 703
ANISOTROPIC NERVE GRAFTS 709
NATURAL NERVE GRAFTS 710
ANIMAL MODELS 711
SUMMARY 712
REFERENCES 712
Chapter 38. Innovative Regenerative Medicine Approaches to Skin Cell-Based Therapy for Patients with Burn Injuries 717
INTRODUCTION 717
CONVENTIONAL THERAPY AND CURRENT COMMERCIAL PRODUCTS 717
PROBLEMS IN THE FIELD 720
CELL APPLICATION INTO THE WOUND BY SPRAYING 721
PATIENT GROUPS AND SELECTION CRITERIA FOR CLINICAL STUDIES IN THE FIELD OF SKIN CELL-BASED THERAPY DEVELOPMENT IN BURN DISEASE PATIENTS 722
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
SKIN PROGENITOR CELLS 726
REGULATORY ISSUES 728
DISCUSSION 733
ACKNOWLEDGMENT 735
REFERENCES 735
Part VII: Regulations and Ethics 742
Chapter 39. Ethical Considerations 743
ARGUMENTS THAT DO NOT WORK 743
ARGUMENTS THAT WORK 747
MORALITY AND THE SCOPE OF FUNDED RESEARCH 751
ETHICAL CONSTRAINTS 751
ACKNOWLEDGMENT 752
REFERENCES 753
Chapter 40. To Make is to Know: The Ethical Issues in Human Tissue Engineering 755
CASE STUDY 755
ARE THERE REASONS IN PRINCIPLE WHY PERFORMING THE BASIC RESEARCH SHOULD BE IMPERMISSIBLE? 756
DUTY AND HEALING: NATURAL MAKERS IN A BROKEN WORLD 757
TO MAKE IS TO KNOW: NOTES ON AN OLD PROBLEM ABOUT KNOWLEDGE 758
WHAT IS A THING: THE PERILS OF DECONSTRUCTION? 759
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
WHAT PURPOSES, TECHNIQUES, OR APPLICATIONS WOULD BE PERMISSIBLE AND UNDER WHAT CIRCUMSTANCES? 760
WHAT PROCEDURES, STRUCTURES, INVOLVING WHAT POLICIES, SHOULD BE USED TO DECIDE ON APPROPRIATE TECHNIQUES AND USES? 761
CONCLUSION 762
Chapter 41. Overview of FDA Regulatory Process 763
INTRODUCTION AND CHAPTER OVERVIEW 763
BRIEF LEGISLATIVE HISTORY OF FDA 763
LAWS, REGULATIONS, AND GUIDANCE 764
FDA ORGANIZATION AND JURISDICTIONAL ISSUES 766
APPROVAL MECHANISMS AND CLINICAL STUDIES 767
MEETINGS WITH INDUSTRY, PROFESSIONAL GROUPS, AND SPONSORS 768
REGULATIONS AND GUIDANCE OF SPECIAL INTEREST FOR REGENERATIVE MEDICINE 769
ADVISORY COMMITTEE MEETINGS 776
FDA AND CRITICAL PATH SCIENCE 777
CONCLUSION 778
REFERENCES 778
Chapter 42. Current Issues in US Patent Law 783
WHAT ARE INTELLECTUAL PROPERTY RIGHTS? 783
WHY ARE INTELLECTUAL PROPERTY RIGHTS IMPORTANT? 793
HOW DO YOU VALUE INTELLECTUAL PROPERTY? 795
Index 799
A 799
B 800
C 802
D 805
E 806
F 807
G 808
H 808
I 809
J 811
K 811
L 811
M 812
N 814
O 815
P 816
Q 818
R 818
S 818
T 821
U 822
V 823
W 823
X 823
Z 823