Suchen und Finden
Service
Foundations of Regenerative Medicine - Clinical and Therapeutic Applications
Anthony Atala
Verlag Elsevier Reference Monographs, 2009
ISBN 9780123785626 , 823 Seiten
Format PDF, ePUB, OL
Kopierschutz DRM
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 β-CELL REPLACEMENT THERAPY
238
CURRENT LIMITATIONS TO β-CELL REPLACEMENT THERAPY
240
ALTERNATIVE SOURCES OF INSULIN-PRODUCING CELLS: STEM CELLS AND β-CELL REGENERATION
241
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