Elsevier S & T

Principles of Regenerative Medicine

Atala, Anthony; Lanza, Robert; Nerem, Robert; Thomson, James A.

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Table of contents

Contentsvii
Prefacexiii
List of Contributorsxv
Part I: Introduction to Regenerative Medicine1
Chapter 1. Current and Future Perspectives of Regenerative Medicine2
REGENERATIVE MEDICINE: CURRENT AND FUTURE PERSPECTIVES2
CONCLUSIONS10
REFERENCES10
Chapter 2. Fundamentals of Cell-Based Therapies16
INTRODUCTION16
RATIONALE FOR CELL-BASED THERAPIES16
CONCLUSIONS23
ACKNOWLEDGMENTS24
REFERENCES24
Chapter 3. Stem Cell Research28
INTRODUCTION28
STEM CELLS29
STEM CELL MODULATION IN VITRO35
REGENERATIVE MEDICINE38
CONCLUSION42
ACKNOWLEDGMENTS42
INTERNET RESOURCES42
REFERENCES42
Part II: Biologic and Molecular Basis of Regenerative Medicine49
Chapter 4. Molecular Organization of Cells50
INTRODUCTION50
CELLULAR MECHANISMS OF THE EMT50
MOLECULAR CONTROL OF THE EMT53
CONCLUSION59
REFERENCES59
Chapter 5. Cell-ECM Interactions in Repair and Regeneration66
INTRODUCTION66
COMPOSITION AND DIVERSITY OF THE ECM66
RECEPTORS FOR ECM MOLECULES68
SIGNAL TRANSDUCTION EVENTS DURING CELL–ECM INTERACTIONS70
CELL–ECM INTERACTIONS DURING HEALING OF SKIN WOUNDS73
CELL–ECM INTERACTIONS DURING REGENERATION78
IMPLICATIONS FOR REGENERATIVE MEDICINE83
REFERENCES84
Chapter 6. Developmental Mechanisms of Regeneration100
INTRODUCTION100
MECHANISMS OF REGENERATION101
STRATEGIES OF REGENERATIVE MEDICINE109
CONCLUSION117
ACKNOWLEDGMENT118
REFERENCES118
Chapter 7. The Molecular Basis of Pluripotency in Principles of Regenerative Medicine126
INTRODUCTION TO PLURIPOTENCY126
EXTRACELLULAR SIGNALING FACTORS AND SIGNAL TRANSDUCTION127
TRANSCRIPTIONAL NETWORKS131
EPIGENETIC AND ENVIRONMENTAL REGULATION131
SUMMARY AND PERSPECTIVES132
REFERENCES133
Chapter 8. How Do Cells Change Their Phenotype136
INTRODUCTION136
STEM CELLS136
PLASTICITY – TRANSDIFFERENTIATION AND TRANSDETERMINATION137
CELL FUSION138
CELL PHENOTYPE139
CONTROL OF GENE ACTIVITY140
EXTRINSIC CONTROLS141
CONCLUSIONS142
ACKNOWLEDGMENTS143
REFERENCES143
Chapter 9. Somatic Cloning and Epigenetic Reprogramming in Mammals148
INTRODUCTION: SHORT HISTORY OF CLONING148
TECHNICAL ASPECTS OF SOMATIC NT149
SUCCESS RATES OF SOMATIC CLONING AND THE QUESTION OF NORMALITY OF CLONED OFFSPRING151
EPIGENETIC REPROGRAMMING152
APPLICATION OF SOMATIC NT158
CONCLUSIONS160
ACKNOWLEDGMENTS161
REFERENCES161
Chapter 10. Transgenic Cloned Goats and Cows for the Production of Therapeutic Proteins168
INTRODUCTION168
GENERATION OF TRANSGENIC ANIMALS169
SCNT: DONOR CELL LINE DEVELOPMENT AND CHARACTERIZATION170
CAPRINE SCNT173
CONCLUSION184
ACKNOWLEDGMENTS185
REFERENCES185
Part III: Cells and Tissue Development189
Chapter 11. Genetic Approaches in Human Embryonic Stem Cells and Their Derivatives190
INTRODUCTION190
MAINTAINING UNDIFFERENTIATED HESCS191
GENETIC APPROACHES TO MANIPULATING HESCS192
DIFFERENTIATION OF HESCS INTO TISSUE-SPECIFIC LINEAGES AND TRANSPLANTATION OF HESC-DERIVED CELLS198
GENETIC MODIFICATIONS OF HESC-DERIVED PROGENIES201
POTENTIAL APPLICATIONS OF GENETICALLY MANIPULATED HESCS AND THEIR DERIVATIVES201
CONCLUSION203
ACKNOWLEDGMENT203
REFERENCES203
Chapter 12. Embryonic Stem Cells: Derivation and Properties210
INTRODUCTION210
DERIVATION OF ES CELLS210
CULTURE OF ES CELLS212
DEVELOPMENTAL POTENTIAL OF ES CELLS215
CONCLUSION217
ACKNOWLEDGMENT218
REFERENCES218
Chapter 13. Stem Cells Derived from Amniotic Fluid and Placenta226
INTRODUCTION226
CVS AND AMNIOCENTESIS226
DIFFERENTIATED CELLS FROM AMNIOTIC FLUID AND PLACENTA227
MESENCHYMAL CELL FROM PLACENTA AND AMNIOTIC FLUID227
PLURIPOTENT STEM CELLS FROM PLACENTA AND AMNIOTIC FLUID230
FUTURE DIRECTION235
SUMMARY235
REFERENCES235
Chapter 14. Stem Cells Derived from Cord Blood238
INTRODUCTION238
PROCUREMENT AND PROCESSING OF CORD BLOOD239
CORD BLOOD STORAGE240
HEMATOPOIETIC AND TISSUE REGENERATION240
PLURIPOTENT CELLS FROM UMBILICAL CORD BLOOD CELLS241
NEUROLOGICAL REGENERATION241
CONCLUSION251
FUTURE DEVELOPMENTS251
REFERENCES252
Chapter 15. Multipotent Adult Progenitor Cells258
PLURIPOTENT STEM CELLS: EMBRYONIC STEM CELLS258
POSTNATAL TISSUE-SPECIFIC STEM CELLS: ARE SOME MORE THAN MULTIPOTENT?258
ISOLATION OF MAPCs260
DIFFERENTIATION ABILITY OF MAPC IN VITRO261
ENGRAFTMENT OF MAPC IN VIVO261
CONTRIBUTION OF MAPC TO CHIMERAS262
MECHANISM UNDERLYING GREATER POTENCY OF MAPC AND SIMILAR ADULT STEM CELLS WITH GREATER POTENCY262
ACKNOWLEDGMENTS263
REFERENCES263
Chapter 16. Bone Marrow Stem Cells: Properties and Pluripotency268
INTRODUCTION268
BONE MARROW STEM CELLs268
BMSCS AND TISSUE REGENERATION272
IMPORTANT FACTORS REGULATING BMSC HOMING AND DIFFERENTIATION275
CLINICAL APPLICATIONS OF BMSCS FOR CARDIAC REGENERATION278
CONCLUSION278
REFERENCES279
Chapter 17. Hematopoietic Stem Cell Properties, Markers, and Therapeutics284
INTRODUCTION284
DEVELOPMENTAL ORIGIN OF HEMATOPOIESIS285
INTRINSIC REGULATORS OF SELF-RENEWAL285
MULTI-LINEAGE REPOPULATION288
PLAYERS IN HEMATOPOIESIS289
IN VITRO DIFFERENTIATION OF HEMATOPOIETIC LINEAGES290
IN VITRO EXPANSION OF SELF-RENEWING HSCs290
HSC NICHE291
PURIFICATION AND MOLECULAR SIGNATURE OF HSC292
PLASTICITY AND THERAPEUTICS294
CONCLUSIONS295
REFERENCES295
Chapter 18. Neural Stem Cells300
INTRODUCTION – HISTORICAL BACKGROUND300
THE NEURAL STEM CELL301
ANALYSIS OF NEUROGENESIS302
THERAPEUTICS AND CLINICAL APPROACHES305
CONCLUSION311
REFERENCES312
Chapter 19. Mesenchymal Stem Cells318
INTRODUCTION318
THE DEFINITION OF MSCS319
The Stem Cell Nature of MSCs320
SOURCE OF MSCS AND ISOLATION TECHNIQUES321
WHICH TISSUES CONTAIN MSCS?322
SKELETAL TISSUE REGENERATION BY MSCS322
IMMUNOMODULATORY EFFECTS OF MSCS328
NONSKELETAL TISSUE REGENERATION BY MSCS330
CONCLUSIONS332
REFERENCES333
Chapter 20. Hepatic Stem Cells: Lineage Biology and Pluripotency344
INTRODUCTION344
GENERAL ISSUES WITH RESPECT TO STEM CELLS AND MATURATIONAL LINEAGE BIOLOGY344
SOURCING OF HUMAN TISSUE352
THE LIVER AS A STEM CELL AND MATURATIONAL LINEAGE SYSTEM354
CLINICAL, COMMERCIAL, AND RESEARCH APPLICATIONS OF STEM CELLS (WITH A FOCUS ON LIVER)362
ETHICS AND LEGAL ISSUES IN THE USE OF STEM CELLS367
SUMMARY374
ACKNOWLEDGMENTS374
REFERENCES375
Chapter 21. Skeletal Muscle Stem Cells386
INTRODUCTION386
SKELETAL MUSCLE REQUIRES STEM CELL FUNCTION AFTER INJURY OR IN DISEASE387
MUSCLE STEM CELL CRITERIA387
HISTORICAL PERSPECTIVE ON MUSCLE STEM CELL BIOLOGY388
PUTATIVE MUSCLE STEM CELLS AND THEIR DEFINED CHARACTERISTICS390
MUSCLE STEM CELLS IN THEIR NATURAL ENVIRONMENTS IN VIVO391
THE MUSCLE STEM CELL NICHE392
CHALLENGES FACING THE POTENTIAL THERAPEUTIC USE OF MUSCLE STEM CELLS392
CONCLUSION393
REFERENCES394
Chapter 22. Islet Cell Therapy and Pancreatic Stem Cells398
INTRODUCTION398
BENEFITS OF β-CELL REPLACEMENT THERAPY399
CURRENT LIMITATIONS TO β-CELL REPLACEMENT THERAPY401
ALTERNATIVE SOURCES OF INSULIN-PRODUCING CELLS: STEM CELLS AND β-CELL REGENERATION402
PANCREATIC DEVELOPMENT403
ISLET NEOGENESIS FROM ES CELLS404
ISLET NEOGENESIS FROM ADULT STEM CELLS405
TRANSDIFFERENTIATION407
WHAT THE FUTURE MAY HOLD408
ACKNOWLEDGMENTS409
REFERENCES409
Chapter 23. Regenerative Medicine for Diseases of the Retina418
INTRODUCTION418
EFTFs: SPECIFICATION OF THE EYE418
RETINAL PROGENITORS: FROM OPTIC CUP TO RETINA421
RETINAL STEM CELLS AND PERSISTENT PROGENITORS IN ADULT VERTEBRATES: THE CILIARY MARGINAL ZONE424
TRANSDIFFERENTIATION AND RETINAL REGENERATION425
CONCLUSION430
REFERENCES431
Chapter 24. Peripheral Blood Stem Cells438
INTRODUCTION438
TYPES AND SOURCE OF STEM CELLS IN THE PERIPHERAL BLOOD438
EPC439
MSC444
HSC445
THERAPEUTIC APPLICATIONS OF PERIPHERAL BLOOD STEM CELLS445
CONCLUSIONS AND FUTURE DIRECTIONS449
REFERENCES450
Chapter 25. Prospects of Somatic Cell Nuclear Transfer-derived Embryonic Stem Cells in Regenerative456
INTRODUCTION456
BRIEF HISTORY457
STATE OF THE ART459
PROSPECTS AND CHALLENGES461
CONCLUSIONS AND FUTURE DIRECTIONS463
REFERENCES463
Chapter 26. Somatic Cells: Growth and Expansion Potential of T Lymphocytes468
INTRODUCTION468
T CELLS ARE KEY TO IMMUNITY TO INFECTIONS AND CANCER469
GROWTH AND EXPANSION POTENTIAL OF T CELLS469
CELL CULTURE MODELING OF T CELL REPLICATIVE SENESCENCE470
REPLICATIVE SENESCENCE ALSO AFFECTS GENE EXPRESSION AND FUNCTION471
SENESCENT CELLS ARE PRESENT IN VIVO472
SENESCENT CD8 T CELLS ARE ASSOCIATED WITH A VARIETY OF NEGATIVE HEALTH OUTCOMES473
RETARDING OR PREVENTING REPLICATIVE SENESCENCE IN AGING AND HIV DISEASE474
CONCLUDING REMARKS476
ACKNOWLEDGMENTS476
REFERENCES476
Chapter 27. Mechanical Determinants of Tissue Development480
INTRODUCTION480
MECHANICAL FORCES EXPERIENCED BY TISSUES481
THE CELL AS A SIGNAL RECEIVER AND PROCESSOR483
OVERVIEW OF BIOREACTORS490
PRACTICAL EXAMPLES OF MECHANICAL DETERMINANTS491
CONCLUSION495
REFERENCES495
Chapter 28. Morphogenesis and Morphogenetic Proteins498
INTRODUCTION498
BMPS499
STEM CELLS503
SCAFFOLDS OF BIOMIMETIC BIOMATERIALS505
CARTILAGE-DERIVED MORPHOGENETIC PROTEINS506
REGENERATIVE MEDICINE AND SURGERY506
ACKNOWLEDGEMENTS508
REFERENCES508
Chapter 29. Physical Stress as a Factor in Tissue Growth and Remodeling512
INTRODUCTION512
STRUCTURAL HIERARCHY AND THE CONTINUUM CONCEPT513
STRAIN AND STRESS DEFINITIONS513
TISSUE GROWTH, REPAIR, AND REMODELING519
MECHANOTRANSDUCTION MECHANISMS521
IN VITRO MECHANICAL CONDITIONING525
CONCLUSIONS530
REFERENCES530
Chapter 30. Engineering Cellular Microenvironments536
INTRODUCTION536
DEFINING THE CELLULAR MICROENVIRONMENT537
DEFINING THE ORGANIZATION OF MULTICELLULAR CONSTRUCTS544
DYNAMICALLY CHANGING THE MICROENVIRONMENT548
CONCLUSIONS AND FUTURE DIRECTIONS549
ACKNOWLEDGMENTS550
REFERENCES550
Chapter 31. Applications of Nanotechnology554
INTRODUCTION554
NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR CELL-BASED THERAPIES556
NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR BIOMATERIAL CONTROL558
CONCLUSION559
REFERENCES560
Chapter 32. GeneChips in Regenerative Medicine562
INTRODUCTION562
PROTOCOL563
STEM CELL DIFFERENTIATION569
CELL SCREENING573
RE-ENGINEERING HEALTHY FROM DISEASED TISSUE574
APPLICATIONS TO CANCER574
CONCLUSION576
SUMMARY576
REFERENCES576
Part IV: Biomaterials for Regenerative Medicine579
Chapter 33. Design Principles in Biomaterials and Scaffolds580
INTRODUCTION580
SELECTION OF BIOMATERIALS581
BIODEGRADABLE SYNTHETIC POLYMERS581
DESIGN PRINCIPLES OF BIOLOGICAL SCAFFOLDS582
SUMMARY AND CONCLUSION590
REFERENCES591
Chapter 34. Naturally Occurring Scaffold Materials594
INTRODUCTION594
COLLAGEN594
CHITOSAN595
INTACT EXTRACELLULAR MATRIX AS A SCAFFOLD MATERIAL597
REFERENCES598
Chapter 35. Synthetic Polymers604
INTRODUCTION604
NON-DEGRADABLE SYNTHETIC POLYMERS606
BIODEGRADABLE SYNTHETIC POLYMERS FOR REGENERATIVE MEDICINE613
APPLICATIONS OF SYNTHETIC POLYMERS625
CONCLUSION/SUMMARY626
REFERENCES626
Chapter 36. Hybrid, Composite, and Complex Biomaterials for Scaffolds636
INTRODUCTION636
BIOMATERIALS FOR TISSUE ENGINEERING636
HYBRID AND COMPOSITE SCAFFOLDS BIOMATERIALS FOR TISSUE ENGINEERING639
SYNTHETIC/NATURAL HYBRID SCAFFOLD FOR TISSUE ENGINEERED INTERVERTEVERAL DISK648
CONCLUSIONS651
ACKNOWLEDGMENTS651
REFERENCES651
Chapter 37. Surface Modification of Biomaterials656
INTRODUCTION656
PHYSICOCHEMICAL SURFACE MODIFICATIONS657
OVERCOATING TECHNOLOGIES660
BIOLOGICAL MODIFICATION OF SURFACES662
SURFACE CHEMICAL PATTERNING664
CONCLUSION AND FUTURE PROSPECTS664
REFERENCES665
Chapter 38. Cell–Substrate Interactions666
INTRODUCTION666
CELL-ECM INTERACTIONS666
CELL-SUBSTRATE INTERACTIONS667
CONCLUSION680
ACKNOWLEDGMENT681
REFERENCES681
Chapter 39. Histogenesis in Three-Dimensional Scaffolds686
REPLACING DISEASED TISSUES686
CONCLUSIONS699
REFERENCES699
Chapter 40. Biocompatibility and Bioresponse to Biomaterials704
INTRODUCTION704
INFLAMMATION (INNATE IMMUNITY) AND WOUND HEALING705
FIBROSIS AND FIBROUS ENCAPSULATION713
IMMUNOTOXICITY (ACQUIRED IMMUNITY)714
SUMMARY720
REFERENCES721
Chapter 41. Essential Elements of Wound Healing724
INTRODUCTION724
REGULATION OF TISSUE HEALING724
INFLAMMATION725
FIBROPLASIA726
NEOVASCULARIZATION728
RE-EPITHELIALIZATION729
WOUND CONTRACTION729
REGENERATIVE DERMAL HEALING: FETAL HEALING730
CONCLUSIONS730
REFERENCES731
Chapter 42. Proteins Controlled with Precision at Organic, Polymeric, and Biopolymer Interfaces for734
INTRODUCTION734
NON-SPECIFIC PROTEIN ADSORPTION735
INHIBITION OF NON-SPECIFIC PROTEIN ADSORPTION736
CONTROLLING PROTEINS AT INTERFACES WITH PRECISION737
IMPLICATIONS AND PERSPECTIVES740
ACKNOWLEDGMENTS740
REFERENCES740
Part V: Therapeutic Applications: Cell Therapy743
Chapter 43. Biomineralization and Bone Regeneration744
DEVELOPMENT AND FRACTURE HEALING OF BONE744
PRINCIPLE OF BONE TISSUE ENGINEERING745
STEM CELLS IN BONE TISSUE ENGINEERING745
GROWTH/DIFFERENTIATION FACTORS IN BONE TISSUE ENGINEERING747
SCAFFOLDS FOR BONE TISSUE ENGINEERING748
CONCLUSIONS752
REFERENCES753
Chapter 44. Blood Substitutes: Reverse Evolution from Oxygen Carrying to Non-Oxygen Carrying Plasma756
INDICATIONS FOR BLOOD TRANSFUSION756
BIOMATERIAL-BASED BLOOD SUBSTITUTES757
CARDIOVASCULAR BIOMECHANICS (FUNCTIONAL CAPILLARY DENSITY MODEL)759
CELLULAR-BASED BLOOD SUBSTITUTES761
CLINICAL TRIALS – ETHICAL CONSIDERATIONS762
REFERENCES763
Chapter 45. Articular Cartilage766
INTRODUCTION766
CELL THERAPIES768
CELL–SCAFFOLD IMPLANTS774
SCAFFOLD-FREE CONSTRUCTS776
CURRENT CLINICAL OUTCOMES776
SUMMARY777
ACKNOWLEDGMENT777
REFERENCES778
Chapter 46. Implantation of Myogenic Cells in Skeletal Muscles782
INTRODUCTION782
CELLS TO GRAFT782
CELL IMPLANTATION785
CELL SURVIVAL IN THE RECIPIENT788
CONCLUSIONS790
REFERENCES790
Chapter 47. Islet Cell Transplantation794
INTRODUCTION794
CLINICAL ISLET TRANSPLANTATION798
RISKS TO THE RECIPIENT800
FUTURE CHALLENGES801
SUMMARY AND CONCLUSIONS806
REFERENCES807
Chapter 48. Cell-Based Repair for Cardiovascular Regeneration and Neovascularization: What, Why, How812
INTRODUCTION812
THE STATE OF CELL THERAPY813
CELL-BASED REPAIR AS A MEANS OF REGENERATION IN CVD814
VASCULAR INTEGRITY IS A BALANCING ACT IN WHICH INFLAMMATION IS KEY: INJURY VERSUS REPAIR815
REPARATIVE POTENTIAL OF CELL THERAPY820
CLINICAL STUDIES831
WHAT IS REQUIRED FOR SUCCESSFUL REPAIR IN 2007 AND BEYOND?834
SUMMARY839
ACKNOWLEDGMENTS840
REFERENCES840
Chapter 49. Retinal Pigment Epithelium Derived from Embryonic Stem Cells852
DEVELOPMENT OF RPE852
CHARACTERISTICS OF RPE853
TRANSDIFFERENTIATION OF RPE IN CULTURE853
TRANSPLANTATION OF RPE854
GENERATION OF RPE FROM ES CELL855
CULTURE AND PROPERTIES OF HES-DERIVED RPE859
ACKNOWLEDGMENTS861
REFERENCES861
Chapter 50. Cell Therapies for Bone Regeneration868
INTRODUCTION868
CURRENT SOURCES OF OSTEOGENIC CELLS AND CELL ISOLATION TECHNIQUES872
PRECLINICAL AND CLINICAL RESULTS876
CONCLUSION: FUTURE DEVELOPMENTS AND CHALLENGES883
REFERENCES884
Chapter 51. Cell-Based Therapies for Musculoskeletal Repair888
INTRODUCTION888
BIOLOGY OF CELLS IN MUSCULOSKELETAL TISSUES888
EMBRYONIC AND ADULT STEM CELLS890
CELL-BASED THERAPIES AND TISSUE ENGINEERING896
CONCLUSIONS AND PROSPECTS905
ACKNOWLEDGEMENTS906
REFERENCES906
Chapter 52. Hepatocyte Transplantation912
INTRODUCTION912
BACKGROUND STUDIES914
CLINICAL HEPATOCYTE TRANSPLANTATION916
HEPATOCYTE TRANSPLANTATION NOVEL USES, CHALLENGES, AND FUTURE DIRECTIONS921
SUMMARY922
REFERENCES923
Chapter 53. Bioartificial Livers928
INTRODUCTION928
STRATEGIES FOR EX VIVO MAINTENANCE OF CELLS928
BIOARTIFICIAL LIVER DESIGNS930
HF BIOREACTORS SUCCESSFUL WITH LIVER933
METHODS OF INTRODUCTION OF CELLS TO THE CELL COMPARTMENT934
COMPUTER-REGULATED BIOREACTORS934
MODELING FOR FUTURE DESIGN IMPROVEMENTS935
BIOLOGICAL AND CELL SOURCING ISSUES936
FUNCTIONAL ANALYSIS937
STATIC VERSUS DYNAMIC NUTRIENT INPUTS938
MRI AND NMRS ANALYSES OF BIOARTIFICIAL LIVERS938
CRYOSECTIONING939
DISCUSSION940
SUMMARY941
ACKNOWLEDGEMENTS941
REFERENCES942
Chapter 54. Neuronal Transplantation for Stroke946
INTRODUCTION946
THE BASIS OF CELLULAR TRANSPLANTATION946
POTENTIAL MECHANISMS OF CELL TRANSPLANTATION947
PRODUCTION OF NEURONAL CELLS FOR HUMAN USE948
INSTITUTIONAL PREPARATION OF NEURONAL CELLS948
CLINICAL TRIAL DESIGN948
NEURONAL TRANSPLANTATION TECHNIQUE949
FUNCTIONAL OUTCOMES950
ACTION RESEARCH ARM TEST951
COGNITIVE TESTING951
IMAGING951
SAFETY AND FEASIBILITY IN STROKE PATIENTS951
GOING FORWARD952
REFERENCES952
Chapter 55. Cell-Based Drug Delivery954
INTRODUCTION954
CELLS AND CELL PRODUCTS AS DRUG SOURCES954
CELL ENCAPSULATION FOR THERAPEUTIC DELIVERY MACHINERY955
CELL-BASED PROTEIN FACTORY960
DRUG-LOADED TUMOR CELL SYSTEM961
SUMMARY963
REFERENCES963
Part VI: Therapeutic Applications: Tissue Therapy967
Chapter 56. Fetal Tissues968
INTRODUCTION968
STEM CELLS DERIVED FROM FETAL TISSUES969
IMMUNOLOGICAL CONSIDERATIONS969
ETHICAL CONSIDERATIONS: FETUS AND OOCYTES969
REGENERATIVE MEDICINE APPLICATIONS OF FETAL TISSUES970
CONCLUSIONS975
REFERENCES975
Chapter 57. Engineering of Large Diameter Vessels978
INTRODUCTION978
PREVALENCE AND IMPACT OF VASCULAR DISEASE978
THE NEED FOR IMPROVED DIALYSIS VASCULAR ACCESS979
VASCULAR PHYSIOLOGY RELEVANT TO TEBVs980
TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE LITERATURE984
TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE PROCESS985
REFERENCES995
Chapter 58. Engineering of Small Diameter Vessels1000
INTRODUCTION1000
CELL SOURCING CONSIDERATIONS1003
SCAFFOLDS FOR SMALL DIAMETER TISSUE-ENGINEERED VESSELS1005
CELLULAR INTERACTIONS1010
BIOREACTOR CULTURES1011
IN VIVO CONSTRUCT FABRICATION1012
CONCLUSION1012
REFERENCES1013
Chapter 59. Vascular Assembly in Engineered and Natural Tissues1020
INTRODUCTION1020
VASCULAR ASSEMBLY: BASIC MECHANISMS1020
GENES AND PROTEINS1023
BIOMATERIALS1024
CELL THERAPIES1026
VASCULARIZATION IN VITRO1028
VASCULARIZATION IN VIVO1029
ANALYSIS AND ASSESSMENT1030
CONCLUSIONS1033
REFERENCES1033
Chapter 60. Cardiac Tissue1038
INTRODUCTION: FROM TISSUES TO ORGANS: KEY GOALS AND ISSUES1038
CELL AND GENE THERAPY1039
SCAFFOLD-BASED APPROACHES1042
TISSUE AND ORGAN FUNCTION1046
BIOREACTORS AND CONDITIONING1050
IMPLANTATION OF CARDIAC PATCHES1052
SUMMARY1053
REFERENCES1053
Chapter 61. Regenerative Medicine in the Cornea1060
INTRODUCTION: THE NEED FOR REGENERATIVE MEDICINE IN THE CORNEA1060
DESIGN REQUIREMENTS FOR HUMAN CORNEAL REPLACEMENTS1061
KERATOPROSTHESES1062
CELL-BASED HUMAN CORNEAL EQUIVALENTS1066
CONCLUSIONS AND FUTURE PERSPECTIVE1068
REFERENCES1069
Chapter 62. Alimentary Tract1072
INTRODUCTION1072
INTESTINAL DEVELOPMENT AND IMMUNE FUNCTION1073
THE ESOPHAGUS1074
THE SMALL BOWEL1076
THE STOMACH AND COLON1080
CONCLUSION1082
REFERENCES1082
Chapter 63. Liver Cell-Based Therapy – Bioreactors as Enabling Technology1086
NEED FOR INNOVATIVE THERAPIES IN LIVER DISEASE1086
METHODS OF LIVER SUPPORT1086
PROSPECTS OF THE USE OF HEPATIC CELLS FOR EXTRACORPOREAL LIVER SUPPORT1087
THE SOURCE OF CELLS FOR LIVER SUPPORT1091
HUMAN LIVER CELLS IN BIOREACTORS FOR LIVER SUPPORT1093
BIOREACTOR CULTURE OF LIVER CELLS AND CLINICAL APPLICATIONS OF OUR OWN DEVELOPMENT1093
THE CONCEPT OF MODULAR LIVER SUPPORT1094
LIVER PROGENITOR CELLS AND BIOREACTOR CULTURES TO STUDY CELL SOURCES FOR EXTRACORPOREAL LIVER SUPPOR1096
CHALLENGES REGARDING STEM CELL RESEARCH FOR LIVER SUPPORT DEVELOPMENT1097
BIOREACTOR TECHNOLOGY OVERVIEW FOR STEM CELL CULTURE1098
REFERENCES1099
Chapter 64. Intracorporeal Kidney Support1106
INTRODUCTION1106
BASIC PRINCIPLES OF KIDNEY TISSUE REGENERATION1106
CREATION OF RENAL STRUCTURES IN VIVO1108
REGENERATION OF FUNCTIONAL RENAL TISSUE IN VIVO1109
SUMMARY1111
REFERENCES1111
Chapter 65. The Kidney1114
INTRODUCTION1114
ISOLATION AND CULTURE OF PROXIMAL TUBULE CELLS1115
TRANSPORT AND METABOLIC CHARACTERISTICS OF HOLLOW-FIBER BIOREACTORS1115
PRECLINICAL CHARACTERIZATION OF THE RENAL TUBULE ASSIST DEVICE (RAD)1116
CELL THERAPY OF ACUTE RENAL FAILURE DUE TO SEPSIS1117
CLINICAL EXPERIENCE WITH A HUMAN RENAL TUBULE ASSIST DEVICE1118
BIOARTIFICIAL KIDNEY IN ESRD1119
CELL SOURCING1119
ULTRAFILTRATION MEMBRANE DEVELOPMENT1121
REFERENCES1123
Chapter 66. Genitourinary System1126
INTRODUCTION1126
RECONSTITUTION STRATEGIES1126
THE ROLE OF BIOMATERIALS1126
VASCULARIZATION1127
PROGRESS IN TISSUE ENGINEERING OF UROLOGIC STRUCTURES1127
ADDITIONAL APPLICATIONS1132
CONCLUSION1134
ACKNOWLEDGMENTS1135
REFERENCES1135
Chapter 67. Tissue Engineering of the Reproductive System1138
INTRODUCTION1138
MALE1139
FEMALE1152
REFERENCES1159
Chapter 68. Therapeutic Opportunities for Bone Grafting1164
INTRODUCTION1164
APPENDICULAR SKELETON1165
AXIAL SKELETON1168
CRANIOFACIAL SKELETON1170
ACKNOWLEDGMENT1173
REFERENCES1173
Chapter 69. Cartilage Tissue Engineering1176
CLINICAL NEED FOR CARTILAGE REPAIR1176
TISSUE ENGINEERING OVERVIEW1177
CELL-BASED CARTILAGE ENGINEERING IN VITRO1179
BIOMATERIALS IN CARTILAGE REPAIR1183
SUCCESSFUL IN VITRO CARTILAGE ENGINEERING1187
TRANSLATION OF CARTILAGE TISSUE ENGINEERING1189
CURRENT AND FUTURE TRENDS IN CARTILAGE ENGINEERING1190
REFERENCES1191
Chapter 70. Phalanges and Small Joints1198
INTRODUCTION1198
BASIC PRINCIPLES OF ENGINEERING PHALANGES AND SMALL JOINTS1199
CREATION OF COMPOSITE TISSUE STRUCTURES1201
SUMMARY AND FUTURE PERSPECTIVES IN CLINICAL TRANSLATION1203
REFERENCES1204
Chapter 71. Functional Tissue Engineering of Ligament and Tendon Injuries1206
INTRODUCTION1206
NORMAL LIGAMENTS AND TENDONS1207
HEALING OF LIGAMENTS AND TENDONS1211
MCL OF THE KNEE1212
APPLICATION OF FTE1214
SUMMARY AND FUTURE DIRECTIONS1221
ACKNOWLEDGMENT1222
REFERENCES1222
Chapter 72. Tissue Therapy: Implications of Regenerative Medicine for Skeletal Muscle1232
INTRODUCTION1232
THE NATURAL HEALING PROCESS OF SKELETAL MUSCLE1232
THE ROLE OF INFLAMMATION IN SKELETAL MUSCLE HEALING1235
PROMOTING REGENERATION AFTER SKELETAL MUSCLE INJURY1238
FIBROSIS PREVENTION: ANOTHER APPROACH TO IMPROVING SKELETAL MUSCLE HEALING1240
CONCLUSION1241
REFERENCES1242
Chapter 73. Tissue Therapy: Central Nervous System1248
INTRODUCTION1248
ANIMAL MODELS1250
STRATEGIES FOR REPAIR AND REGENERATION1252
CONCLUSIONS AND OUTLOOK1263
ACKNOWLEDGMENTS1263
REFERENCES1263
Chapter 74. Peripheral Nerve Regeneration1270
INTRODUCTION1270
ISOTROPIC NERVE GRAFTS FOR REGENERATION1272
ANISOTROPIC NERVE GRAFTS1278
NATURAL NERVE GRAFTS1279
ANIMAL MODELS1280
SUMMARY1281
REFERENCES1281
Chapter 75. Dental Tissue Engineering1286
INTRODUCTION1286
CONCLUSIONS1293
ACKNOWLEDGMENTS1293
REFERENCES1294
Chapter 76. Innovative Regenerative Medicine Approaches to Skin Cell-Based Therapy for Patients with1298
INTRODUCTION1298
CONVENTIONAL THERAPY AND CURRENT COMMERCIAL PRODUCTS1298
PROBLEMS IN THE FIELD1301
CELL APPLICATION INTO THE WOUND BY SPRAYING1302
PATIENT GROUPS AND SELECTION CRITERIA FOR CLINICAL STUDIES IN THE FIELD OF SKIN CELL-BASED THERAPY D1303
INITIAL OWN CASE REPORTS SHOW THAT THE SPRAY TRANSPLANTATION METHOD WITH IN VITRO EXPANDED KERATINOC1305
SKIN PROGENITOR CELLS1307
REGULATORY ISSUES1309
DISCUSSION1314
ACKNOWLEDGMENT1316
REFERENCES1316
Chapter 77. Military Needs and Solutions in Regenerative Medicine1322
INTRODUCTION1322
THE APPLICATION OF TISSUE ENGINEERING TO COMBAT CASUALTY CARE1322
CONCLUSION1329
ACKNOWLEDGMENTS1330
REFERENCES1330
Part VII: Regulations and Ethics1333
Chapter 78. Ethical Considerations1334
ARGUMENTS THAT DO NOT WORK1334
ARGUMENTS THAT WORK1338
MORALITY AND THE SCOPE OF FUNDED RESEARCH1342
ETHICAL CONSTRAINTS1342
ACKNOWLEDGMENT1343
REFERENCES1344
Chapter 79. To Make is to Know: The Ethical Issues in Human Tissue Engineering1346
CASE STUDY1346
ARE THERE REASONS IN PRINCIPLE WHY PERFORMING THE BASIC RESEARCH SHOULD BE IMPERMISSIBLE?1347
DUTY AND HEALING: NATURAL MAKERS IN A BROKEN WORLD1348
TO MAKE IS TO KNOW: NOTES ON AN OLD PROBLEM ABOUT KNOWLEDGE1349
WHAT IS A THING: THE PERILS OF DECONSTRUCTION?1350
WHAT CONTEXTUAL FACTORS SURROUNDING THE TECHNOLOGY HAVE TO BE TAKEN INTO ACCOUNT AND DO ANY OF THESE1350
WHAT PURPOSES, TECHNIQUES, OR APPLICATIONS WOULD BE PERMISSIBLE AND UNDER WHAT CIRCUMSTANCES?1351
WHAT PROCEDURES, STRUCTURES, INVOLVING WHAT POLICIES, SHOULD BE USED TO DECIDE ON APPROPRIATE TECHNI1352
CONCLUSION1353
Chapter 80. US Stem Cell Research Policy1354
INTRODUCTION1354
SOURCES OF STEM CELLS1354
EMBRYONIC STEM CELL RESEARCH: CURRENT US LAW AND POLICY1355
INTERNATIONAL COMPARISONS1357
STATE AND PRIVATE FUNDING IN THE UNITED STATES1358
POLICY AS EMBRYONIC STEM CELL RESEARCH MOVES FORWARD1359
GUIDELINES FROM THE NATIONAL ACADEMIES1359
COMPENSATING EGG DONORS: THE ARGUMENTS1361
COMMERCIALIZATION AND ACCESS1362
CONCLUSION1363
ACKNOWLEDGMENTS1363
REFERENCES1363
Chapter 81. Overview of FDA Regulatory Process1366
INTRODUCTION AND CHAPTER OVERVIEW1366
BRIEF LEGISLATIVE HISTORY OF FDA1366
LAWS, REGULATIONS, AND GUIDANCE1367
FDA ORGANIZATION AND JURISDICTIONAL ISSUES1369
APPROVAL MECHANISMS AND CLINICAL STUDIES1370
MEETINGS WITH INDUSTRY, PROFESSIONAL GROUPS, AND SPONSORS1371
REGULATIONS AND GUIDANCE OF SPECIAL INTEREST FOR REGENERATIVE MEDICINE1372
ADVISORY COMMITTEE MEETINGS1379
FDA AND CRITICAL PATH SCIENCE1380
CONCLUSION1381
REFERENCES1381
Chapter 82. Current Issues in US Patent Law1386
WHAT ARE INTELLECTUAL PROPERTY RIGHTS?1386
WHY ARE INTELLECTUAL PROPERTY RIGHTS IMPORTANT?1396
HOW DO YOU VALUE INTELLECTUAL PROPERTY?1398
Index1402
A1402
B1405
C1408
D1413
E1414
F1416
G1418
H1419
I1422
J1424
K1425
L1425
M1426
N1430
O1432
P1433
Q1437
R1437
S1438
T1443
U1445
V1446
W1447
X1448
Y1448
Z1448

Book details

Vendor Elsevier S & T
SKU 9780123694102
ISBN-13 9780080555959
Author Atala, Anthony; Lanza, Robert; Nerem, Robert; Thomson, James A.
Category Medical
Subject Biotechnology

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Virtually any disease that results from malfunctioning, damaged, or failing tissues may be potentially cured through regenerative medicine therapies, by either regenerating the damaged tissues in vivo, or by growing the tissues and organs in vitro and implanting them into the patient. Principles of Regenerative Medicine discusses the latest advances in technology and medicine for 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.

* Key for all researchers and instituions in Stem Cell Biology, Bioengineering, and Developmental Biology
* The first of its kind to offer an advanced understanding of the latest technologies in regenerative medicine
* New discoveries from leading researchers on restoration of diseased tissues and organs

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