Principles of Regenerative Medicine

Front Cover......Page 1
Principles of Regenerative Medicine......Page 4
ISBN 0123694108......Page 5
Part III Cells and Tissue Development......Page 8
Part V Therapeutic Applications: Cell Therapy......Page 10
Part VI Therapeutic Applications: Tissue Therapy......Page 11
Part VII Regulations and Ethics......Page 12
Preface......Page 14
List of Contributors......Page 16
Part I: Introduction to Regenerative Medicine......Page 26
REGENERATIVE MEDICINE: CURRENT AND FUTURE PERSPECTIVES......Page 27
REFERENCES......Page 35
RATIONALE FOR CELL-BASED THERAPIES......Page 41
CONCLUSIONS......Page 48
REFERENCES......Page 49
INTRODUCTION......Page 53
STEM CELLS......Page 54
STEM CELL MODULATION IN VITRO......Page 60
REGENERATIVE MEDICINE......Page 63
REFERENCES......Page 67
Part II: Biologic and Molecular Basis of Regenerative Medicine......Page 74
CELLULAR MECHANISMS OF THE EMT......Page 75
MOLECULAR CONTROL OF THE EMT......Page 78
REFERENCES......Page 84
COMPOSITION AND DIVERSITY OF THE ECM......Page 91
RECEPTORS FOR ECM MOLECULES......Page 93
SIGNAL TRANSDUCTION EVENTS DURING CELL–ECM INTERACTIONS......Page 95
CELL–ECM INTERACTIONS DURING HEALING OF SKIN WOUNDS......Page 98
CELL–ECM INTERACTIONS DURING REGENERATION......Page 103
IMPLICATIONS FOR REGENERATIVE MEDICINE......Page 108
REFERENCES......Page 109
INTRODUCTION......Page 125
MECHANISMS OF REGENERATION......Page 126
STRATEGIES OF REGENERATIVE MEDICINE......Page 134
CONCLUSION......Page 142
REFERENCES......Page 143
INTRODUCTION TO PLURIPOTENCY......Page 151
EXTRACELLULAR SIGNALING FACTORS AND SIGNAL TRANSDUCTION......Page 152
EPIGENETIC AND ENVIRONMENTAL REGULATION......Page 156
SUMMARY AND PERSPECTIVES......Page 157
REFERENCES......Page 158
STEM CELLS......Page 161
PLASTICITY – TRANSDIFFERENTIATION AND TRANSDETERMINATION......Page 162
CELL FUSION......Page 163
CELL PHENOTYPE......Page 164
CONTROL OF GENE ACTIVITY......Page 165
EXTRINSIC CONTROLS......Page 166
CONCLUSIONS......Page 167
REFERENCES......Page 168
INTRODUCTION: SHORT HISTORY OF CLONING......Page 173
TECHNICAL ASPECTS OF SOMATIC NT......Page 174
SUCCESS RATES OF SOMATIC CLONING AND THE QUESTION OF NORMALITY OF CLONED OFFSPRING......Page 176
EPIGENETIC REPROGRAMMING......Page 177
APPLICATION OF SOMATIC NT......Page 183
CONCLUSIONS......Page 185
REFERENCES......Page 186
INTRODUCTION......Page 193
GENERATION OF TRANSGENIC ANIMALS......Page 194
SCNT: DONOR CELL LINE DEVELOPMENT AND CHARACTERIZATION......Page 195
CAPRINE SCNT......Page 198
CONCLUSION......Page 209
REFERENCES......Page 210
Part III: Cells and Tissue Development......Page 214
INTRODUCTION......Page 215
MAINTAINING UNDIFFERENTIATED HESCS......Page 216
GENETIC APPROACHES TO MANIPULATING HESCS......Page 217
DIFFERENTIATION OF HESCS INTO TISSUE-SPECIFIC LINEAGES AND TRANSPLANTATION OF HESC-DERIVED CELLS......Page 223
POTENTIAL APPLICATIONS OF GENETICALLY MANIPULATED HESCS AND THEIR DERIVATIVES......Page 226
REFERENCES......Page 228
DERIVATION OF ES CELLS......Page 235
CULTURE OF ES CELLS......Page 237
DEVELOPMENTAL POTENTIAL OF ES CELLS......Page 240
CONCLUSION......Page 242
REFERENCES......Page 243
CVS AND AMNIOCENTESIS......Page 251
MESENCHYMAL CELL FROM PLACENTA AND AMNIOTIC FLUID......Page 252
PLURIPOTENT STEM CELLS FROM PLACENTA AND AMNIOTIC FLUID......Page 255
REFERENCES......Page 260
INTRODUCTION......Page 263
PROCUREMENT AND PROCESSING OF CORD BLOOD......Page 264
HEMATOPOIETIC AND TISSUE REGENERATION......Page 265
NEUROLOGICAL REGENERATION......Page 266
FUTURE DEVELOPMENTS......Page 276
REFERENCES......Page 277
POSTNATAL TISSUE-SPECIFIC STEM CELLS: ARE SOME MORE THAN MULTIPOTENT?......Page 283
ISOLATION OF MAPCs......Page 285
ENGRAFTMENT OF MAPC IN VIVO......Page 286
MECHANISM UNDERLYING GREATER POTENCY OF MAPC AND SIMILAR ADULT STEM CELLS WITH GREATER POTENCY......Page 287
REFERENCES......Page 288
BONE MARROW STEM CELLs......Page 293
BMSCS AND TISSUE REGENERATION......Page 297
IMPORTANT FACTORS REGULATING BMSC HOMING AND DIFFERENTIATION......Page 300
CONCLUSION......Page 303
REFERENCES......Page 304
INTRODUCTION......Page 309
INTRINSIC REGULATORS OF SELF-RENEWAL......Page 310
MULTI-LINEAGE REPOPULATION......Page 313
PLAYERS IN HEMATOPOIESIS......Page 314
IN VITRO EXPANSION OF SELF-RENEWING HSCs......Page 315
HSC NICHE......Page 316
PURIFICATION AND MOLECULAR SIGNATURE OF HSC......Page 317
PLASTICITY AND THERAPEUTICS......Page 319
REFERENCES......Page 320
INTRODUCTION – HISTORICAL BACKGROUND......Page 325
THE NEURAL STEM CELL......Page 326
ANALYSIS OF NEUROGENESIS......Page 327
THERAPEUTICS AND CLINICAL APPROACHES......Page 330
CONCLUSION......Page 336
REFERENCES......Page 337
INTRODUCTION......Page 343
THE DEFINITION OF MSCS......Page 344
The Stem Cell Nature of MSCs......Page 345
SOURCE OF MSCS AND ISOLATION TECHNIQUES......Page 346
SKELETAL TISSUE REGENERATION BY MSCS......Page 347
IMMUNOMODULATORY EFFECTS OF MSCS......Page 353
NONSKELETAL TISSUE REGENERATION BY MSCS......Page 355
CONCLUSIONS......Page 357
REFERENCES......Page 358
GENERAL ISSUES WITH RESPECT TO STEM CELLS AND MATURATIONAL LINEAGE BIOLOGY......Page 369
SOURCING OF HUMAN TISSUE......Page 377
THE LIVER AS A STEM CELL AND MATURATIONAL LINEAGE SYSTEM......Page 379
CLINICAL, COMMERCIAL, AND RESEARCH APPLICATIONS OF STEM CELLS (WITH A FOCUS ON LIVER)......Page 387
ETHICS AND LEGAL ISSUES IN THE USE OF STEM CELLS......Page 392
ACKNOWLEDGMENTS......Page 399
REFERENCES......Page 400
INTRODUCTION......Page 411
MUSCLE STEM CELL CRITERIA......Page 412
HISTORICAL PERSPECTIVE ON MUSCLE STEM CELL BIOLOGY......Page 413
PUTATIVE MUSCLE STEM CELLS AND THEIR DEFINED CHARACTERISTICS......Page 415
MUSCLE STEM CELLS IN THEIR NATURAL ENVIRONMENTS IN VIVO......Page 416
CHALLENGES FACING THE POTENTIAL THERAPEUTIC USE OF MUSCLE STEM CELLS......Page 417
CONCLUSION......Page 418
REFERENCES......Page 419
INTRODUCTION......Page 423
BENEFITS OF β-CELL REPLACEMENT THERAPY......Page 424
CURRENT LIMITATIONS TO β-CELL REPLACEMENT THERAPY......Page 426
ALTERNATIVE SOURCES OF INSULIN-PRODUCING CELLS: STEM CELLS AND β-CELL REGENERATION......Page 427
PANCREATIC DEVELOPMENT......Page 428
ISLET NEOGENESIS FROM ES CELLS......Page 429
ISLET NEOGENESIS FROM ADULT STEM CELLS......Page 430
TRANSDIFFERENTIATION......Page 432
WHAT THE FUTURE MAY HOLD......Page 433
REFERENCES......Page 434
EFTFs: SPECIFICATION OF THE EYE......Page 443
RETINAL PROGENITORS: FROM OPTIC CUP TO RETINA......Page 446
RETINAL STEM CELLS AND PERSISTENT PROGENITORS IN ADULT VERTEBRATES: THE CILIARY MARGINAL ZONE......Page 449
TRANSDIFFERENTIATION AND RETINAL REGENERATION......Page 450
CONCLUSION......Page 455
REFERENCES......Page 456
TYPES AND SOURCE OF STEM CELLS IN THE PERIPHERAL BLOOD......Page 463
EPC......Page 464
MSC......Page 469
THERAPEUTIC APPLICATIONS OF PERIPHERAL BLOOD STEM CELLS......Page 470
CONCLUSIONS AND FUTURE DIRECTIONS......Page 474
REFERENCES......Page 475
INTRODUCTION......Page 481
BRIEF HISTORY......Page 482
STATE OF THE ART......Page 484
PROSPECTS AND CHALLENGES......Page 486
REFERENCES......Page 488
INTRODUCTION......Page 493
GROWTH AND EXPANSION POTENTIAL OF T CELLS......Page 494
CELL CULTURE MODELING OF T CELL REPLICATIVE SENESCENCE......Page 495
REPLICATIVE SENESCENCE ALSO AFFECTS GENE EXPRESSION AND FUNCTION......Page 496
SENESCENT CELLS ARE PRESENT IN VIVO......Page 497
SENESCENT CD8 T CELLS ARE ASSOCIATED WITH A VARIETY OF NEGATIVE HEALTH OUTCOMES......Page 498
RETARDING OR PREVENTING REPLICATIVE SENESCENCE IN AGING AND HIV DISEASE......Page 499
REFERENCES......Page 501
INTRODUCTION......Page 505
MECHANICAL FORCES EXPERIENCED BY TISSUES......Page 506
THE CELL AS A SIGNAL RECEIVER AND PROCESSOR......Page 508
OVERVIEW OF BIOREACTORS......Page 515
PRACTICAL EXAMPLES OF MECHANICAL DETERMINANTS......Page 516
REFERENCES......Page 520
INTRODUCTION......Page 523
BMPS......Page 524
STEM CELLS......Page 528
SCAFFOLDS OF BIOMIMETIC BIOMATERIALS......Page 530
REGENERATIVE MEDICINE AND SURGERY......Page 531
REFERENCES......Page 533
INTRODUCTION......Page 537
STRAIN AND STRESS DEFINITIONS......Page 538
TISSUE GROWTH, REPAIR, AND REMODELING......Page 544
MECHANOTRANSDUCTION MECHANISMS......Page 546
IN VITRO MECHANICAL CONDITIONING......Page 550
REFERENCES......Page 555
INTRODUCTION......Page 561
DEFINING THE CELLULAR MICROENVIRONMENT......Page 562
DEFINING THE ORGANIZATION OF MULTICELLULAR CONSTRUCTS......Page 569
DYNAMICALLY CHANGING THE MICROENVIRONMENT......Page 573
CONCLUSIONS AND FUTURE DIRECTIONS......Page 574
REFERENCES......Page 575
INTRODUCTION......Page 579
NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR CELL-BASED THERAPIES......Page 581
NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR BIOMATERIAL CONTROL......Page 583
CONCLUSION......Page 584
REFERENCES......Page 585
INTRODUCTION......Page 587
PROTOCOL......Page 588
STEM CELL DIFFERENTIATION......Page 594
CELL SCREENING......Page 598
APPLICATIONS TO CANCER......Page 599
REFERENCES......Page 601
Part IV: Biomaterials for Regenerative Medicine......Page 604
INTRODUCTION......Page 605
BIODEGRADABLE SYNTHETIC POLYMERS......Page 606
DESIGN PRINCIPLES OF BIOLOGICAL SCAFFOLDS......Page 607
SUMMARY AND CONCLUSION......Page 615
REFERENCES......Page 616
COLLAGEN......Page 619
CHITOSAN......Page 620
INTACT EXTRACELLULAR MATRIX AS A SCAFFOLD MATERIAL......Page 622
REFERENCES......Page 623
INTRODUCTION......Page 629
NON-DEGRADABLE SYNTHETIC POLYMERS......Page 631
BIODEGRADABLE SYNTHETIC POLYMERS FOR REGENERATIVE MEDICINE......Page 638
APPLICATIONS OF SYNTHETIC POLYMERS......Page 650
REFERENCES......Page 651
BIOMATERIALS FOR TISSUE ENGINEERING......Page 661
HYBRID AND COMPOSITE SCAFFOLDS BIOMATERIALS FOR TISSUE ENGINEERING......Page 664
SYNTHETIC/NATURAL HYBRID SCAFFOLD FOR TISSUE ENGINEERED INTERVERTEVERAL DISK......Page 673
REFERENCES......Page 676
INTRODUCTION......Page 681
PHYSICOCHEMICAL SURFACE MODIFICATIONS......Page 682
OVERCOATING TECHNOLOGIES......Page 685
BIOLOGICAL MODIFICATION OF SURFACES......Page 687
CONCLUSION AND FUTURE PROSPECTS......Page 689
REFERENCES......Page 690
CELL-ECM INTERACTIONS......Page 691
CELL-SUBSTRATE INTERACTIONS......Page 692
CONCLUSION......Page 705
REFERENCES......Page 706
REPLACING DISEASED TISSUES......Page 711
REFERENCES......Page 724
INTRODUCTION......Page 729
INFLAMMATION (INNATE IMMUNITY) AND WOUND HEALING......Page 730
FIBROSIS AND FIBROUS ENCAPSULATION......Page 738
IMMUNOTOXICITY (ACQUIRED IMMUNITY)......Page 739
SUMMARY......Page 745
REFERENCES......Page 746
REGULATION OF TISSUE HEALING......Page 749
INFLAMMATION......Page 750
FIBROPLASIA......Page 751
NEOVASCULARIZATION......Page 753
WOUND CONTRACTION......Page 754
CONCLUSIONS......Page 755
REFERENCES......Page 756
INTRODUCTION......Page 759
NON-SPECIFIC PROTEIN ADSORPTION......Page 760
INHIBITION OF NON-SPECIFIC PROTEIN ADSORPTION......Page 761
CONTROLLING PROTEINS AT INTERFACES WITH PRECISION......Page 762
REFERENCES......Page 765
Part V: Therapeutic Applications: Cell Therapy......Page 768
DEVELOPMENT AND FRACTURE HEALING OF BONE......Page 769
STEM CELLS IN BONE TISSUE ENGINEERING......Page 770
GROWTH/DIFFERENTIATION FACTORS IN BONE TISSUE ENGINEERING......Page 772
SCAFFOLDS FOR BONE TISSUE ENGINEERING......Page 773
CONCLUSIONS......Page 777
REFERENCES......Page 778
INDICATIONS FOR BLOOD TRANSFUSION......Page 781
BIOMATERIAL-BASED BLOOD SUBSTITUTES......Page 782
CARDIOVASCULAR BIOMECHANICS (FUNCTIONAL CAPILLARY DENSITY MODEL)......Page 784
CELLULAR-BASED BLOOD SUBSTITUTES......Page 786
CLINICAL TRIALS – ETHICAL CONSIDERATIONS......Page 787
REFERENCES......Page 788
INTRODUCTION......Page 791
CELL THERAPIES......Page 793
CELL–SCAFFOLD IMPLANTS......Page 799
CURRENT CLINICAL OUTCOMES......Page 801
ACKNOWLEDGMENT......Page 802
REFERENCES......Page 803
CELLS TO GRAFT......Page 807
CELL IMPLANTATION......Page 810
CELL SURVIVAL IN THE RECIPIENT......Page 813
REFERENCES......Page 815
INTRODUCTION......Page 819
CLINICAL ISLET TRANSPLANTATION......Page 823
RISKS TO THE RECIPIENT......Page 825
FUTURE CHALLENGES......Page 826
SUMMARY AND CONCLUSIONS......Page 831
REFERENCES......Page 832
INTRODUCTION......Page 837
THE STATE OF CELL THERAPY......Page 838
CELL-BASED REPAIR AS A MEANS OF REGENERATION IN CVD......Page 839
VASCULAR INTEGRITY IS A BALANCING ACT IN WHICH INFLAMMATION IS KEY: INJURY VERSUS REPAIR......Page 840
REPARATIVE POTENTIAL OF CELL THERAPY......Page 845
CLINICAL STUDIES......Page 856
WHAT IS REQUIRED FOR SUCCESSFUL REPAIR IN 2007 AND BEYOND?......Page 859
SUMMARY......Page 864
REFERENCES......Page 865
DEVELOPMENT OF RPE......Page 877
TRANSDIFFERENTIATION OF RPE IN CULTURE......Page 878
TRANSPLANTATION OF RPE......Page 879
GENERATION OF RPE FROM ES CELL......Page 880
CULTURE AND PROPERTIES OF HES-DERIVED RPE......Page 884
REFERENCES......Page 886
INTRODUCTION......Page 893
CURRENT SOURCES OF OSTEOGENIC CELLS AND CELL ISOLATION TECHNIQUES......Page 897
PRECLINICAL AND CLINICAL RESULTS......Page 901
CONCLUSION: FUTURE DEVELOPMENTS AND CHALLENGES......Page 908
REFERENCES......Page 909
BIOLOGY OF CELLS IN MUSCULOSKELETAL TISSUES......Page 913
EMBRYONIC AND ADULT STEM CELLS......Page 915
CELL-BASED THERAPIES AND TISSUE ENGINEERING......Page 921
CONCLUSIONS AND PROSPECTS......Page 930
REFERENCES......Page 931
INTRODUCTION......Page 937
BACKGROUND STUDIES......Page 939
CLINICAL HEPATOCYTE TRANSPLANTATION......Page 941
HEPATOCYTE TRANSPLANTATION NOVEL USES, CHALLENGES, AND FUTURE DIRECTIONS......Page 946
SUMMARY......Page 947
REFERENCES......Page 948
STRATEGIES FOR EX VIVO MAINTENANCE OF CELLS......Page 953
BIOARTIFICIAL LIVER DESIGNS......Page 955
HF BIOREACTORS SUCCESSFUL WITH LIVER......Page 958
COMPUTER-REGULATED BIOREACTORS......Page 959
MODELING FOR FUTURE DESIGN IMPROVEMENTS......Page 960
BIOLOGICAL AND CELL SOURCING ISSUES......Page 961
FUNCTIONAL ANALYSIS......Page 962
MRI AND NMRS ANALYSES OF BIOARTIFICIAL LIVERS......Page 963
CRYOSECTIONING......Page 964
DISCUSSION......Page 965
ACKNOWLEDGEMENTS......Page 966
REFERENCES......Page 967
THE BASIS OF CELLULAR TRANSPLANTATION......Page 971
POTENTIAL MECHANISMS OF CELL TRANSPLANTATION......Page 972
CLINICAL TRIAL DESIGN......Page 973
NEURONAL TRANSPLANTATION TECHNIQUE......Page 974
FUNCTIONAL OUTCOMES......Page 975
SAFETY AND FEASIBILITY IN STROKE PATIENTS......Page 976
REFERENCES......Page 977
CELLS AND CELL PRODUCTS AS DRUG SOURCES......Page 979
CELL ENCAPSULATION FOR THERAPEUTIC DELIVERY MACHINERY......Page 980
CELL-BASED PROTEIN FACTORY......Page 985
DRUG-LOADED TUMOR CELL SYSTEM......Page 986
REFERENCES......Page 988
Part VI: Therapeutic Applications: Tissue Therapy......Page 992
INTRODUCTION......Page 993
ETHICAL CONSIDERATIONS: FETUS AND OOCYTES......Page 994
REGENERATIVE MEDICINE APPLICATIONS OF FETAL TISSUES......Page 995
REFERENCES......Page 1000
PREVALENCE AND IMPACT OF VASCULAR DISEASE......Page 1003
THE NEED FOR IMPROVED DIALYSIS VASCULAR ACCESS......Page 1004
VASCULAR PHYSIOLOGY RELEVANT TO TEBVs......Page 1005
TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE LITERATURE......Page 1009
TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE PROCESS......Page 1010
REFERENCES......Page 1020
INTRODUCTION......Page 1025
CELL SOURCING CONSIDERATIONS......Page 1028
SCAFFOLDS FOR SMALL DIAMETER TISSUE-ENGINEERED VESSELS......Page 1030
CELLULAR INTERACTIONS......Page 1035
BIOREACTOR CULTURES......Page 1036
CONCLUSION......Page 1037
REFERENCES......Page 1038
VASCULAR ASSEMBLY: BASIC MECHANISMS......Page 1045
GENES AND PROTEINS......Page 1048
BIOMATERIALS......Page 1049
CELL THERAPIES......Page 1051
VASCULARIZATION IN VITRO......Page 1053
VASCULARIZATION IN VIVO......Page 1054
ANALYSIS AND ASSESSMENT......Page 1055
REFERENCES......Page 1058
INTRODUCTION: FROM TISSUES TO ORGANS: KEY GOALS AND ISSUES......Page 1063
CELL AND GENE THERAPY......Page 1064
SCAFFOLD-BASED APPROACHES......Page 1067
TISSUE AND ORGAN FUNCTION......Page 1071
BIOREACTORS AND CONDITIONING......Page 1075
IMPLANTATION OF CARDIAC PATCHES......Page 1077
REFERENCES......Page 1078
INTRODUCTION: THE NEED FOR REGENERATIVE MEDICINE IN THE CORNEA......Page 1085
DESIGN REQUIREMENTS FOR HUMAN CORNEAL REPLACEMENTS......Page 1086
KERATOPROSTHESES......Page 1087
CELL-BASED HUMAN CORNEAL EQUIVALENTS......Page 1091
CONCLUSIONS AND FUTURE PERSPECTIVE......Page 1093
REFERENCES......Page 1094
INTRODUCTION......Page 1097
INTESTINAL DEVELOPMENT AND IMMUNE FUNCTION......Page 1098
THE ESOPHAGUS......Page 1099
THE SMALL BOWEL......Page 1101
THE STOMACH AND COLON......Page 1105
REFERENCES......Page 1107
METHODS OF LIVER SUPPORT......Page 1111
PROSPECTS OF THE USE OF HEPATIC CELLS FOR EXTRACORPOREAL LIVER SUPPORT......Page 1112
THE SOURCE OF CELLS FOR LIVER SUPPORT......Page 1116
BIOREACTOR CULTURE OF LIVER CELLS AND CLINICAL APPLICATIONS OF OUR OWN DEVELOPMENT......Page 1118
THE CONCEPT OF MODULAR LIVER SUPPORT......Page 1119
LIVER PROGENITOR CELLS AND BIOREACTOR CULTURES TO STUDY CELL SOURCES FOR EXTRACORPOREAL LIVER SUPPORT......Page 1121
CHALLENGES REGARDING STEM CELL RESEARCH FOR LIVER SUPPORT DEVELOPMENT......Page 1122
BIOREACTOR TECHNOLOGY OVERVIEW FOR STEM CELL CULTURE......Page 1123
REFERENCES......Page 1124
BASIC PRINCIPLES OF KIDNEY TISSUE REGENERATION......Page 1131
CREATION OF RENAL STRUCTURES IN VIVO......Page 1133
REGENERATION OF FUNCTIONAL RENAL TISSUE IN VIVO......Page 1134
REFERENCES......Page 1136
INTRODUCTION......Page 1139
TRANSPORT AND METABOLIC CHARACTERISTICS OF HOLLOW-FIBER BIOREACTORS......Page 1140
PRECLINICAL CHARACTERIZATION OF THE RENAL TUBULE ASSIST DEVICE (RAD)......Page 1141
CELL THERAPY OF ACUTE RENAL FAILURE DUE TO SEPSIS......Page 1142
CLINICAL EXPERIENCE WITH A HUMAN RENAL TUBULE ASSIST DEVICE......Page 1143
CELL SOURCING......Page 1144
ULTRAFILTRATION MEMBRANE DEVELOPMENT......Page 1146
REFERENCES......Page 1148
THE ROLE OF BIOMATERIALS......Page 1151
PROGRESS IN TISSUE ENGINEERING OF UROLOGIC STRUCTURES......Page 1152
ADDITIONAL APPLICATIONS......Page 1157
CONCLUSION......Page 1159
REFERENCES......Page 1160
INTRODUCTION......Page 1163
MALE......Page 1164
FEMALE......Page 1177
REFERENCES......Page 1184
INTRODUCTION......Page 1189
APPENDICULAR SKELETON......Page 1190
AXIAL SKELETON......Page 1193
CRANIOFACIAL SKELETON......Page 1195
REFERENCES......Page 1198
CLINICAL NEED FOR CARTILAGE REPAIR......Page 1201
TISSUE ENGINEERING OVERVIEW......Page 1202
CELL-BASED CARTILAGE ENGINEERING IN VITRO......Page 1204
BIOMATERIALS IN CARTILAGE REPAIR......Page 1208
SUCCESSFUL IN VITRO CARTILAGE ENGINEERING......Page 1212
TRANSLATION OF CARTILAGE TISSUE ENGINEERING......Page 1214
CURRENT AND FUTURE TRENDS IN CARTILAGE ENGINEERING......Page 1215
REFERENCES......Page 1216
INTRODUCTION......Page 1223
BASIC PRINCIPLES OF ENGINEERING PHALANGES AND SMALL JOINTS......Page 1224
CREATION OF COMPOSITE TISSUE STRUCTURES......Page 1226
SUMMARY AND FUTURE PERSPECTIVES IN CLINICAL TRANSLATION......Page 1228
REFERENCES......Page 1229
INTRODUCTION......Page 1231
NORMAL LIGAMENTS AND TENDONS......Page 1232
HEALING OF LIGAMENTS AND TENDONS......Page 1236
MCL OF THE KNEE......Page 1237
APPLICATION OF FTE......Page 1239
SUMMARY AND FUTURE DIRECTIONS......Page 1246
REFERENCES......Page 1247
THE NATURAL HEALING PROCESS OF SKELETAL MUSCLE......Page 1257
THE ROLE OF INFLAMMATION IN SKELETAL MUSCLE HEALING......Page 1260
PROMOTING REGENERATION AFTER SKELETAL MUSCLE INJURY......Page 1263
FIBROSIS PREVENTION: ANOTHER APPROACH TO IMPROVING SKELETAL MUSCLE HEALING......Page 1265
CONCLUSION......Page 1266
REFERENCES......Page 1267
INTRODUCTION......Page 1273
ANIMAL MODELS......Page 1275
STRATEGIES FOR REPAIR AND REGENERATION......Page 1277
REFERENCES......Page 1288
INTRODUCTION......Page 1295
ISOTROPIC NERVE GRAFTS FOR REGENERATION......Page 1297
ANISOTROPIC NERVE GRAFTS......Page 1303
NATURAL NERVE GRAFTS......Page 1304
ANIMAL MODELS......Page 1305
REFERENCES......Page 1306
INTRODUCTION......Page 1311
ACKNOWLEDGMENTS......Page 1318
REFERENCES......Page 1319
CONVENTIONAL THERAPY AND CURRENT COMMERCIAL PRODUCTS......Page 1323
PROBLEMS IN THE FIELD......Page 1326
CELL APPLICATION INTO THE WOUND BY SPRAYING......Page 1327
PATIENT GROUPS AND SELECTION CRITERIA FOR CLINICAL STUDIES IN THE FIELD OF SKIN CELL-BASED THERAPY DEVELOPMENT IN BURN DISEASE PATIENTS......Page 1328
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…......Page 1330
SKIN PROGENITOR CELLS......Page 1332
REGULATORY ISSUES......Page 1334
DISCUSSION......Page 1339
REFERENCES......Page 1341
THE APPLICATION OF TISSUE ENGINEERING TO COMBAT CASUALTY CARE......Page 1347
CONCLUSION......Page 1354
REFERENCES......Page 1355
Part VII: Regulations and Ethics......Page 1358
ARGUMENTS THAT DO NOT WORK......Page 1359
ARGUMENTS THAT WORK......Page 1363
ETHICAL CONSTRAINTS......Page 1367
ACKNOWLEDGMENT......Page 1368
REFERENCES......Page 1369
CASE STUDY......Page 1371
ARE THERE REASONS IN PRINCIPLE WHY PERFORMING THE BASIC RESEARCH SHOULD BE IMPERMISSIBLE?......Page 1372
DUTY AND HEALING: NATURAL MAKERS IN A BROKEN WORLD......Page 1373
TO MAKE IS TO KNOW: NOTES ON AN OLD PROBLEM ABOUT KNOWLEDGE......Page 1374
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?......Page 1375
WHAT PURPOSES, TECHNIQUES, OR APPLICATIONS WOULD BE PERMISSIBLE AND UNDER WHAT CIRCUMSTANCES?......Page 1376
WHAT PROCEDURES, STRUCTURES, INVOLVING WHAT POLICIES, SHOULD BE USED TO DECIDE ON APPROPRIATE TECHNIQUES AND USES?......Page 1377
CONCLUSION......Page 1378
SOURCES OF STEM CELLS......Page 1379
EMBRYONIC STEM CELL RESEARCH: CURRENT US LAW AND POLICY......Page 1380
INTERNATIONAL COMPARISONS......Page 1382
STATE AND PRIVATE FUNDING IN THE UNITED STATES......Page 1383
GUIDELINES FROM THE NATIONAL ACADEMIES......Page 1384
COMPENSATING EGG DONORS: THE ARGUMENTS......Page 1386
COMMERCIALIZATION AND ACCESS......Page 1387
REFERENCES......Page 1388
BRIEF LEGISLATIVE HISTORY OF FDA......Page 1391
LAWS, REGULATIONS, AND GUIDANCE......Page 1392
FDA ORGANIZATION AND JURISDICTIONAL ISSUES......Page 1394
APPROVAL MECHANISMS AND CLINICAL STUDIES......Page 1395
MEETINGS WITH INDUSTRY, PROFESSIONAL GROUPS, AND SPONSORS......Page 1396
REGULATIONS AND GUIDANCE OF SPECIAL INTEREST FOR REGENERATIVE MEDICINE......Page 1397
ADVISORY COMMITTEE MEETINGS......Page 1404
FDA AND CRITICAL PATH SCIENCE......Page 1405
REFERENCES......Page 1406
WHAT ARE INTELLECTUAL PROPERTY RIGHTS?......Page 1411
WHY ARE INTELLECTUAL PROPERTY RIGHTS IMPORTANT?......Page 1421
HOW DO YOU VALUE INTELLECTUAL PROPERTY?......Page 1423
A......Page 1427
B......Page 1430
C......Page 1433
D......Page 1438
E......Page 1439
F......Page 1441
G......Page 1443
H......Page 1444
I......Page 1447
J......Page 1449
L......Page 1450
M......Page 1451
N......Page 1455
O......Page 1457
P......Page 1458
R......Page 1462
S......Page 1463
T......Page 1468
U......Page 1470
V......Page 1471
W......Page 1472
Z......Page 1473