Foundations of Regenerative Medicine: Clinical and Therapeutic Applications

Foundations of Regenerative Medicine......Page 4
Copyright Page......Page 5
Contents......Page 8
Preface......Page 12
List of Contributors......Page 24
Part I: Introduction to Regenerative Medicine......Page 30
REGENERATIVE MEDICINE: CURRENT AND FUTURE PERSPECTIVES......Page 31
REFERENCES......Page 39
RATIONALE FOR CELL-BASED THERAPIES......Page 45
CONCLUSIONS......Page 52
REFERENCES......Page 53
INTRODUCTION......Page 57
STEM CELLS......Page 58
STEM CELL MODULATION IN VITRO......Page 64
REGENERATIVE MEDICINE......Page 67
REFERENCES......Page 71
Part II: Biologic and Molecular Basis for Regenerative Medicine......Page 78
CELLULAR MECHANISMS OF THE EMT......Page 79
MOLECULAR CONTROL OF THE EMT......Page 82
REFERENCES......Page 88
COMPOSITION AND DIVERSITY OF THE ECM......Page 95
RECEPTORS FOR ECM MOLECULES......Page 97
SIGNAL TRANSDUCTION EVENTS DURING CELL–ECM INTERACTIONS......Page 99
CELL–ECM INTERACTIONS DURING HEALING OF SKIN WOUNDS......Page 102
CELL–ECM INTERACTIONS DURING REGENERATION......Page 107
IMPLICATIONS FOR REGENERATIVE MEDICINE......Page 112
REFERENCES......Page 113
INTRODUCTION......Page 129
MECHANISMS OF REGENERATION......Page 130
STRATEGIES OF REGENERATIVE MEDICINE......Page 138
CONCLUSION......Page 146
REFERENCES......Page 147
INTRODUCTION TO PLURIPOTENCY......Page 155
EXTRACELLULAR SIGNALING FACTORS AND SIGNAL TRANSDUCTION......Page 156
EPIGENETIC AND ENVIRONMENTAL REGULATION......Page 160
SUMMARY AND PERSPECTIVES......Page 161
REFERENCES......Page 162
Part III: Cells and Tissue Development......Page 166
DERIVATION OF ES CELLS......Page 167
CULTURE OF ES CELLS......Page 169
DEVELOPMENTAL POTENTIAL OF ES CELLS......Page 172
CONCLUSION......Page 174
REFERENCES......Page 175
CVS AND AMNIOCENTESIS......Page 183
MESENCHYMAL CELL FROM PLACENTA AND AMNIOTIC FLUID......Page 184
PLURIPOTENT STEM CELLS FROM PLACENTA AND AMNIOTIC FLUID......Page 187
REFERENCES......Page 192
BONE MARROW STEM CELLs......Page 195
BMSCS AND TISSUE REGENERATION......Page 199
IMPORTANT FACTORS REGULATING BMSC HOMING AND DIFFERENTIATION......Page 202
CONCLUSION......Page 205
REFERENCES......Page 206
INTRODUCTION......Page 211
THE DEFINITION OF MSCs......Page 212
THE STEM CELL NATURE OF MSCs......Page 213
SOURCE OF MSCs AND ISOLATION TECHNIQUES......Page 214
SKELETAL TISSUE REGENERATION BY MSCs......Page 215
IMMUNOMODULATORY EFFECTS OF MSCs......Page 221
NONSKELETAL TISSUE REGENERATION BY MSCs......Page 223
CONCLUSIONS......Page 225
REFERENCES......Page 226
INTRODUCTION......Page 237
BENEFITS OF β-CELL REPLACEMENT THERAPY......Page 238
CURRENT LIMITATIONS TO β-CELL REPLACEMENT THERAPY......Page 240
ALTERNATIVE SOURCES OF INSULIN-PRODUCING CELLS: STEM CELLS AND β-CELL REGENERATION......Page 241
PANCREATIC DEVELOPMENT......Page 242
ISLET NEOGENESIS FROM ES CELLS......Page 243
ISLET NEOGENESIS FROM ADULT STEM CELLS......Page 244
TRANSDIFFERENTIATION......Page 246
WHAT THE FUTURE MAY HOLD......Page 247
REFERENCES......Page 248
INTRODUCTION......Page 257
MECHANICAL FORCES EXPERIENCED BY TISSUES......Page 258
THE CELL AS A SIGNAL RECEIVER AND PROCESSOR......Page 260
OVERVIEW OF BIOREACTORS......Page 267
PRACTICAL EXAMPLES OF MECHANICAL DETERMINANTS......Page 268
REFERENCES......Page 272
INTRODUCTION......Page 275
BMPs......Page 276
STEM CELLS......Page 280
SCAFFOLDS OF BIOMIMETIC BIOMATERIALS......Page 282
REGENERATIVE MEDICINE AND SURGERY......Page 283
REFERENCES......Page 285
INTRODUCTION......Page 289
STRAIN AND STRESS DEFINITIONS......Page 290
TISSUE GROWTH, REPAIR, AND REMODELING......Page 296
MECHANOTRANSDUCTION MECHANISMS......Page 298
IN VITRO MECHANICAL CONDITIONING......Page 302
REFERENCES......Page 307
INTRODUCTION......Page 313
DEFINING THE CELLULAR MICROENVIRONMENT......Page 314
DEFINING THE ORGANIZATION OF MULTICELLULAR CONSTRUCTS......Page 321
DYNAMICALLY CHANGING THE MICROENVIRONMENT......Page 325
CONCLUSIONS AND FUTURE DIRECTIONS......Page 326
REFERENCES......Page 327
INTRODUCTION......Page 331
NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR CELL-BASED THERAPIES......Page 333
NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR BIOMATERIAL CONTROL......Page 335
CONCLUSION......Page 336
REFERENCES......Page 337
Part IV: Biomaterials for Regenerative Medicine......Page 340
INTRODUCTION......Page 341
BIODEGRADABLE SYNTHETIC POLYMERS......Page 342
DESIGN PRINCIPLES OF BIOLOGICAL SCAFFOLDS......Page 343
SUMMARY AND CONCLUSION......Page 351
REFERENCES......Page 352
COLLAGEN......Page 355
CHITOSAN......Page 356
INTACT EXTRACELLULAR MATRIX AS A SCAFFOLD MATERIAL......Page 358
REFERENCES......Page 359
INTRODUCTION......Page 365
NON-DEGRADABLE SYNTHETIC POLYMERS......Page 367
BIODEGRADABLE SYNTHETIC POLYMERS FOR REGENERATIVE MEDICINE......Page 374
APPLICATIONS OF SYNTHETIC POLYMERS......Page 386
REFERENCES......Page 387
INTRODUCTION......Page 397
PHYSICOCHEMICAL SURFACE MODIFICATIONS......Page 398
OVERCOATING TECHNOLOGIES......Page 401
BIOLOGICAL MODIFICATION OF SURFACES......Page 403
CONCLUSION AND FUTURE PROSPECTS......Page 405
REFERENCES......Page 406
INTRODUCTION......Page 407
INFLAMMATION (INNATE IMMUNITY) AND WOUND HEALING......Page 408
FIBROSIS AND FIBROUS ENCAPSULATION......Page 416
IMMUNOTOXICITY (ACQUIRED IMMUNITY)......Page 417
SUMMARY......Page 423
REFERENCES......Page 424
Part V: Therapeutic Applications: Cell Therapy......Page 428
INTRODUCTION......Page 429
CLINICAL ISLET TRANSPLANTATION......Page 433
RISKS TO THE RECIPIENT......Page 435
FUTURE CHALLENGES......Page 436
SUMMARY AND CONCLUSIONS......Page 441
REFERENCES......Page 442
INTRODUCTION......Page 447
THE STATE OF CELL THERAPY......Page 448
CELL-BASED REPAIR AS A MEANS OF REGENERATION IN CVD......Page 449
VASCULAR INTEGRITY IS A BALANCING ACT IN WHICH INFLAMMATION IS KEY: INJURY VERSUS REPAIR......Page 450
REPARATIVE POTENTIAL OF CELL THERAPY......Page 455
CLINICAL STUDIES......Page 466
WHAT IS REQUIRED FOR SUCCESSFUL REPAIR IN 2007 AND BEYOND?......Page 469
SUMMARY......Page 474
REFERENCES......Page 475
INTRODUCTION......Page 487
CURRENT SOURCES OF OSTEOGENIC CELLS AND CELL ISOLATION TECHNIQUES......Page 491
PRECLINICAL AND CLINICAL RESULTS......Page 495
CONCLUSION: FUTURE DEVELOPMENTS AND CHALLENGES......Page 502
REFERENCES......Page 503
BIOLOGY OF CELLS IN MUSCULOSKELETAL TISSUES......Page 507
EMBRYONIC AND ADULT STEM CELLS......Page 509
CELL-BASED THERAPIES AND TISSUE ENGINEERING......Page 515
CONCLUSIONS AND PROSPECTS......Page 524
REFERENCES......Page 525
INTRODUCTION......Page 531
BACKGROUND STUDIES......Page 533
CLINICAL HEPATOCYTE TRANSPLANTATION......Page 535
HEPATOCYTE TRANSPLANTATION NOVEL USES, CHALLENGES, AND FUTURE DIRECTIONS......Page 540
SUMMARY......Page 541
REFERENCES......Page 542
CELLS AND CELL PRODUCTS AS DRUG SOURCES......Page 547
CELL ENCAPSULATION FOR THERAPEUTIC DELIVERY MACHINERY......Page 548
CELL-BASED PROTEIN FACTORY......Page 553
DRUG-LOADED TUMOR CELL SYSTEM......Page 554
REFERENCES......Page 556
Part VI: Therapeutic Applications: Tissue Therapy......Page 560
PREVALENCE AND IMPACT OF VASCULAR DISEASE......Page 561
THE NEED FOR IMPROVED DIALYSIS VASCULAR ACCESS......Page 562
VASCULAR PHYSIOLOGY RELEVANT TO TEBVs......Page 563
TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE LITERATURE......Page 567
TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE PROCESS......Page 568
REFERENCES......Page 578
INTRODUCTION: FROM TISSUES TO ORGANS: KEY GOALS AND ISSUES......Page 583
CELL AND GENE THERAPY......Page 584
SCAFFOLD-BASED APPROACHES......Page 587
TISSUE AND ORGAN FUNCTION......Page 591
BIOREACTORS AND CONDITIONING......Page 595
IMPLANTATION OF CARDIAC PATCHES......Page 597
REFERENCES......Page 598
BASIC PRINCIPLES OF KIDNEY TISSUE REGENERATION......Page 605
CREATION OF RENAL STRUCTURES IN VIVO......Page 607
REGENERATION OF FUNCTIONAL RENAL TISSUE IN VIVO......Page 608
REFERENCES......Page 610
THE ROLE OF BIOMATERIALS......Page 613
PROGRESS IN TISSUE ENGINEERING OF UROLOGIC STRUCTURES......Page 614
ADDITIONAL APPLICATIONS......Page 619
CONCLUSION......Page 621
REFERENCES......Page 622
INTRODUCTION......Page 625
MALE......Page 626
FEMALE......Page 639
REFERENCES......Page 646
INTRODUCTION......Page 651
BASIC PRINCIPLES OF ENGINEERING PHALANGES AND SMALL JOINTS......Page 652
CREATION OF COMPOSITE TISSUE STRUCTURES......Page 654
SUMMARY AND FUTURE PERSPECTIVES IN CLINICAL TRANSLATION......Page 656
REFERENCES......Page 657
INTRODUCTION......Page 659
NORMAL LIGAMENTS AND TENDONS......Page 660
HEALING OF LIGAMENTS AND TENDONS......Page 664
MCL OF THE KNEE......Page 665
APPLICATION OF FTE......Page 667
SUMMARY AND FUTURE DIRECTIONS......Page 674
REFERENCES......Page 675
THE NATURAL HEALING PROCESS OF SKELETAL MUSCLE......Page 685
THE ROLE OF INFLAMMATION IN SKELETAL MUSCLE HEALING......Page 688
PROMOTING REGENERATION AFTER SKELETAL MUSCLE INJURY......Page 691
FIBROSIS PREVENTION: ANOTHER APPROACH TO IMPROVING SKELETAL MUSCLE HEALING......Page 693
CONCLUSION......Page 694
REFERENCES......Page 695
INTRODUCTION......Page 701
ISOTROPIC NERVE GRAFTS FOR REGENERATION......Page 703
ANISOTROPIC NERVE GRAFTS......Page 709
NATURAL NERVE GRAFTS......Page 710
ANIMAL MODELS......Page 711
REFERENCES......Page 712
CONVENTIONAL THERAPY AND CURRENT COMMERCIAL PRODUCTS......Page 717
PROBLEMS IN THE FIELD......Page 720
CELL APPLICATION INTO THE WOUND BY SPRAYING......Page 721
PATIENT GROUPS AND SELECTION CRITERIA FOR CLINICAL STUDIES IN THE FIELD OF SKIN CELL-BASED THERAPY DEVELOPMENT IN BURN DISEASE PATIENTS......Page 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 THE NECK AND FACE
......Page 724
SKIN PROGENITOR CELLS......Page 726
REGULATORY ISSUES......Page 728
DISCUSSION......Page 733
REFERENCES......Page 735
Part VII: Regulations and Ethics......Page 742
ARGUMENTS THAT DO NOT WORK......Page 743
ARGUMENTS THAT WORK......Page 747
ETHICAL CONSTRAINTS......Page 751
ACKNOWLEDGMENT......Page 752
REFERENCES......Page 753
CASE STUDY......Page 755
ARE THERE REASONS IN PRINCIPLE WHY PERFORMING THE BASIC RESEARCH SHOULD BE IMPERMISSIBLE?......Page 756
DUTY AND HEALING: NATURAL MAKERS IN A BROKEN WORLD......Page 757
TO MAKE IS TO KNOW: NOTES ON AN OLD PROBLEM ABOUT KNOWLEDGE......Page 758
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 759
WHAT PURPOSES, TECHNIQUES, OR APPLICATIONS WOULD BE PERMISSIBLE AND UNDER WHAT CIRCUMSTANCES?......Page 760
WHAT PROCEDURES, STRUCTURES, INVOLVING WHAT POLICIES, SHOULD BE USED TO DECIDE ON APPROPRIATE TECHNIQUES AND USES?......Page 761
CONCLUSION......Page 762
BRIEF LEGISLATIVE HISTORY OF FDA......Page 763
LAWS, REGULATIONS, AND GUIDANCE......Page 764
FDA ORGANIZATION AND JURISDICTIONAL ISSUES......Page 766
APPROVAL MECHANISMS AND CLINICAL STUDIES......Page 767
MEETINGS WITH INDUSTRY, PROFESSIONAL GROUPS, AND SPONSORS......Page 768
REGULATIONS AND GUIDANCE OF SPECIAL INTEREST FOR REGENERATIVE MEDICINE......Page 769
ADVISORY COMMITTEE MEETINGS......Page 776
FDA AND CRITICAL PATH SCIENCE......Page 777
REFERENCES......Page 778
WHAT ARE INTELLECTUAL PROPERTY RIGHTS?......Page 783
WHY ARE INTELLECTUAL PROPERTY RIGHTS IMPORTANT?......Page 793
HOW DO YOU VALUE INTELLECTUAL PROPERTY?......Page 795
A......Page 799
B......Page 800
C......Page 802
D......Page 805
E......Page 806
F......Page 807
H......Page 808
I......Page 809
L......Page 811
M......Page 812
N......Page 814
O......Page 815
P......Page 816
S......Page 818
T......Page 821
U......Page 822
Z......Page 823