Elsevier S & T

Principles of Tissue Engineering

Lanza, Robert; Langer, Robert; Vacanti, Joseph P.

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CONTENTS IN BRIEFv
Table of contentsvii
CONTRIBUTORSxix
FOREWORDxxix
PREFACExxxi
PREFACE TO THE SECOND EDITIONxxxiii
PREFACE TO THE FIRST EDITIONxxxv
Introduction to Tissue Engineering1
Chapter One: The History and Scope of Tissue Engineering3
I. INTRODUCTION3
II. SCIENTIFIC CHALLENGES4
III. CELLS4
IV. MATERIALS5
V. GENERAL SCIENTIFIC ISSUES5
VI. SOCIAL CHALLENGES6
VII. REFERENCES6
Chapter Two: The Challenge of Imitating Nature7
I. INTRODUCTION7
II. CELL TECHNOLOGY8
III. CONSTRUCT TECHNOLOGY10
IV. INTEGRATION INTO THE LIVING SYSTEM11
V. CONCLUDING DISCUSSION12
VI. ACKNOWLEDGMENTS13
VII. REFERENCES13
Chapter Three: Moving into the Clinic15
I. INTRODUCTION15
II. HISTORY OF CLINICAL TISSUE ENGINEERING16
III. STRATEGIES TO ADVANCE TOWARD THE CLINIC20
IV. BRINGING TECHNOLOGY PLATFORMS TO THE CLINICAL SETTING26
V. TRANSITION TO CLINICAL TESTING28
VI. ESTABLISHING A REGULATORY PATHWAY30
VII. CONCLUSIONS30
VIII. ACKNOWLEDGMENTS30
IX. REFERENCES31
Chapter Four: Future Perspectives33
I. CLINICAL NEED33
II. CURRENT STATE OF THE FIELD33
III. CURRENT CHALLENGES34
IV. FUTURE DIRECTIONS34
V. FUTURE CHALLENGES42
VI. REFERENCES42
Part One: The Basis of Growth and Differentiation51
Chapter Five: Molecular Biology of the Cell53
I. INTRODUCTION53
II. THE CELL NUCLEUS54
III. THE CYTOPLASM56
IV. GROWTH AND DEATH58
V. CYTOSKELETON60
VI. CELL ADHESION MOLECULES61
VII. EXTRACELLULAR MATRIX62
VIII. CULTURE MEDIA63
IX. CELLS IN TISSUES64
X. FURTHER READING65
Chapter Six: Organization of Cells into Higher-Ordered Structures67
I. INTRODUCTION67
II. MOLECULAR MECHANISMS OF THE EMT68
III. THE EMT TRANSCRIPTIONAL PROGRAM70
IV. MOLECULAR CONTROL OF THE EMT72
V. CONCLUSION76
VI. REFERENCES76
Chapter Seven: The Dynamics of Cell–ECM Interactions81
I. INTRODUCTION81
II. CELL–ECM INTERACTIONS84
III. SIGNAL TRANSDUCTION EVENTS DURING CELL–ECM INTERACTIONS90
IV. RELEVANCE FOR TISSUE ENGINEERING93
V. REFERENCES95
Chapter Eight: Matrix Molecules and Their Ligands101
I. INTRODUCTION101
II. COLLAGENS „ MAJOR CONSTITUENTS OF ECM102
III. ELASTIC FIBERS AND MICROFIBRILS107
IV. OTHER MULTIFUNCTIONAL PROTEINS IN ECM107
V. PROTEOGLYCANS „ MULTIFUNCTIONAL MOLECULES IN THE EXTRACELLULAR MATRIX AND ON CELL SURFACES111
VI. CONCLUSION112
VII. REFERENCES112
Chapter Nine: Morphogenesis and Tissue Engineering117
I. INTRODUCTION117
II. BONE MORPHOGENETIC PROTEINS (BMPs)118
III. CARTILAGE-DERIVED MORPHOGENETIC PROTEINS (CDMPs)121
IV. PLEIOTROPY AND THRESHOLDS121
V. BMPs BIND TO EXTRACELLULAR MATRIX122
VI. BMP RECEPTORS122
VII. RESPONDING STEM CELLS123
VIII. MORPHOGENS AND GENE THERAPY123
IX. BIOMIMETIC BIOMATERIALS124
X. TISSUE ENGINEERING OF BONES AND JOINTS124
XI. FUTURE CHALLENGES125
XII. ACKNOWLEDGMENTS126
XIII. REFERENCES126
Chapter Ten: Gene Expression, Cell Determination, and Differentiation129
I. INTRODUCTION129
II. DETERMINATION AND DIFFERENTIATION129
III. MyoD AND THE bHLH FAMILY OF DEVELOPMENTAL REGULATORY FACTORS131
IV. MEFs „ COREGULATORS OF DEVELOPMENT132
V. PAX IN DEVELOPMENT132
VI. CONCLUSIONS132
VII. REFERENCES133
Part Two: In Vitro Control of Tissue Development135
Chapter Eleven: Engineering Functional Tissues137
I. INTRODUCTION137
II. KEY CONCEPTS138
III. IN VITRO STUDIES AIMED AT CLINICAL TRANSLATION139
IV. REPRESENTATIVE IN VITRO CULTURE ENVIRONMENTS139
V. CONVECTIVE MIXING, FLOW, AND MASS TRANSFER142
VI. CULTURE DURATION AND MECHANICAL CONDITIONING145
VII. CONCLUSIONS149
VIII. ACKNOWLEDGMENTS150
IX. REFERENCES150
Chapter Twelve: Principles of Tissue Culture and Bioreactor Design155
I. INTRODUCTION155
II. BASIC PRINCIPLES OF CELL AND TISSUE CULTURE155
III. PRINCIPLES OF BIOREACTOR DESIGN164
IV. SUMMARY180
V. ACKNOWLEDGMENTS180
VI. REFERENCES180
Chapter Thirteen: Regulation of Cell Behavior by Extracellular Proteins185
I. INTRODUCTION185
II. THROMBOSPONDIN-1185
III. THROMBOSPONDIN-2187
IV. TENASCIN-C187
V. OSTEOPONTIN188
VI. SPARC189
VII. CONCLUSIONS190
VIII. REFERENCES191
Chapter Fourteen: Growth Factors193
I. INTRODUCTION193
II. WOUND HEALING194
III. GROWTH FACTORS AND CYTOKINES ACTIVE AS EARLY MEDIATORS OF THE INFLAMMATORY PROCESS195
IV. INFLAMMATORY RESPONSE MEDIATORS ACTIVATE TRANSCRIPTION OF QUIESCENT GENES196
V. BIOLOGIC PROPERTIES OF SIG (CHEMOKINE) FAMILY MEMBERS197
VI. REGULATION OF JE GENE EXPRESSION BY GLUCOCORTICOIDS197
VII. GROWTH FACTORS AND ACCELERATED HEALING197
VIII. ROLE OF BASIC FIBROBLAST GROWTH FACTOR AND ANGIOGENESIS199
IX. PLEIOTROPHIN REMODELS TUMOR MICROENVIRONMENT AND STIMULATES ANGIOGENESIS200
X. OTHER ROLES OF GROWTH FACTORS AND CYTOKINES201
XI. CONCLUSIONS201
XII. REFERENCES201
Chapter Fifteen: Mechanochemical Control of Cell Fate Switching207
I. INTRODUCTION207
II. EXTRACELLULAR MATRIX STRUCTURE AND FUNCTION207
III. PATTERN FORMATION THROUGH ECM REMODELING209
IV. MECHANOCHEMICAL SWITCHING BETWEEN CELL FATES210
V. SUMMARY213
VI. THE FUTURE213
VII. ACKNOWLEDGMENTS214
VIII. REFERENCES214
Part Three: In Vivo Synthesis of Tissues and Organs217
Chapter Sixteen: In Vivo Synthesis of Tissues and Organs219
I. INTRODUCTION219
II. MAMMALIAN RESPONSE TO INJURY220
III. METHODS TO TREAT LOSS OF ORGAN FUNCTION221
IV. ACTIVE EXTRACELLULAR MATRIX ANALOGS223
V. BASIC PARAMETERS FOR IN VIVO REGENERATION STUDIES: REPRODUCIBLE, NONREGENERATIVE WOUNDS227
VI. EXAMPLES OF IN VIVO ORGAN REGENERATION228
VII. CONCLUSIONS235
VIII. ACKNOWLEDGMENTS236
IX. REFERENCES236
Part Four: Models for Tissue Engineering239
Chapter Seventeen: Models as Precursors for Prosthetic Devices241
I. INTRODUCTION241
II. PIGMENTATION OF THE LIVING-SKIN EQUIVALENT (LSE) IN VITRO244
III. THE LIVING-SKIN EQUIVALENT AS AN IMMUNOLOGICAL MODEL244
IV. THE LIVING-SKIN EQUIVALENT AS A DISEASE MODEL244
V. WOUND-HEALING MODEL246
VI. VASCULAR MODELS WITHOUT CELLS247
VII. VASCULAR MODELS WITH CELLS ADDED247
VIII. CONCLUSIONS248
IX. REFERENCES249
Chapter Eighteen: Quantitative Aspects251
I. INTRODUCTION251
II. MOLECULAR INTERACTIONS WITH CELLS251
III. MOLECULAR AND CELL TRANSPORT THROUGH TISSUE253
IV. CELL AND TISSUE MECHANICS256
V. REFERENCES260
Part Five: Biomaterials in Tissue Engineering263
Chapter Nineteen: Micro-Scale Patterning of Cells and Their Environment265
I. INTRODUCTION265
II. SOFT LITHOGRAPHY266
III. SELF-ASSEMBLED MONOLAYERS (SAMs)266
IV. MICROCONTACT PRINTING AND MICROFEATURES USED IN CELL BIOLOGY267
V. MICROFLUIDIC PATTERNING272
VI. LAMINAR FLOW PATTERNING272
VII. CONCLUSION AND FUTURE PROSPECTS274
VIII. ACKNOWLEDGMENTS275
IX. REFERENCES275
Chapter Twenty: Cell Interactions with Polymers279
I. INTRODUCTION279
II. METHODS FOR CHARACTERIZING CELL INTERACTIONS WITH POLYMERS279
III. CELL INTERACTIONS WITH POLYMERS283
IV. CELL INTERACTIONS WITH POLYMERS IN SUSPENSION289
V. CELL INTERACTIONS WITH THREE-DIMENSIONAL POLYMER SCAFFOLDS AND GELS291
VI. CELL INTERACTIONS UNIQUE TO THE IN VIVO SETTING292
VII. REFERENCES293
Chapter Twenty-One: Matrix Effects297
I. INTRODUCTION297
II. EXTRACELLULAR MATRIX PROTEINS AND THEIR RECEPTORS297
III. MODEL SYSTEMS FOR STUDY OF MATRIX INTERACTIONS301
IV. CELL PATTERN FORMATION BY SUBSTRATE PATTERNING304
V. CONCLUSIONS304
VI. REFERENCES305
Chapter Twenty-Two: Polymer Scaffold Fabrication309
I. INTRODUCTION309
II. FIBER BONDING310
III. ELECTROSPINNING311
IV. SOLVENT CASTING AND PARTICULATE LEACHING311
V. MELT MOLDING312
VI. MEMBRANE LAMINATION312
VII. EXTRUSION312
VIII. FREEZE-DRYING313
IX. PHASE SEPARATION313
X. HIGH-INTERNAL-PHASE EMULSION313
XI. GAS FOAMING313
XII. POLYMER/CERAMIC COMPOSITE FABRICATION314
XIII. RAPID PROTOTYPING OF SOLID FREE FORMS315
XIV. PEPTIDE SELF-ASSEMBLY316
XV. IN SITU POLYMERIZATION316
XVI. CONCLUSIONS317
XVII. ACKNOWLEDGMENTS317
XVIII. REFERENCES320
Chapter Twenty-Three: Biodegradable Polymers323
I. INTRODUCTION323
II. BIODEGRADABLE POLYMER SELECTION CRITERIA323
III. BIOLOGICALLY DERIVED BIORESORBABLES324
IV. SYNTHETIC POLYMERS327
V. CREATING MATERIALS FOR TISSUE-ENGINEERED PRODUCTS332
VI. CONCLUSION333
VII. REFERENCES333
Chapter Twenty-Four: Micro- and Nanofabricated Scaffolds341
I. INTRODUCTION341
II. ADAPTATION OF TRADITIONAL MICRO-SCALE TECHNIQUES FOR SCAFFOLD FABRICATION342
III. THREE-DIMENSIONAL SCAFFOLDS WITH MICRO-SCALE ARCHITECTURE346
IV. THREE-DIMENSIONAL SCAFFOLD ASSEMBLY348
V. MICROFABRICATION OF CELL-SEEDED SCAFFOLDS352
VI. SUMMARY AND FUTURE DIRECTION356
VII. REFERENCES357
Chapter Twenty-Five: Three-Dimensional Scaffolds359
I. INTRODUCTION359
II. THREE-DIMENSIONAL SCAFFOLD DESIGN AND ENGINEERING360
III. CONCLUSIONS370
IV. REFERENCES371
Part Six: Transplantation of Engineered Cells and Tissues375
Chapter Twenty-Six: Tissue Engineering and Transplantation in the Fetus377
I. INTRODUCTION377
II. GENERAL CHARACTERISTICS OF FETAL CELLS378
III. FETAL TISSUE ENGINEERING379
IV. ETHICAL CONSIDERATIONS384
V. THE FETUS AS A TRANSPLANTATION HOST384
VI. CONCLUSIONS385
VII. REFERENCES386
Chapter Twenty-Seven: Immunomodulation389
I. INTRODUCTION389
II. ORIGIN OF THE DESIGNER TISSUE CONCEPT390
III. FIRST DEMONSTRATION OF THE CONCEPT390
IV. EXPANSION OF RESEARCH ON DESIGNER TISSUES391
V. ANTIBODY MASKING391
VI. GENE ABLATION392
VII. RNA ABLATION393
VIII. ENZYME ABLATION393
IX. MECHANISMS OF GRAFT SURVIVAL AFTER CLASS I DONOR ABLATION OR ANTIBODY MASKING394
X. ROLE OF CLASS I MODIFICATIONS IN RESISTANCE TO RECURRENT AUTOIMMUNITY395
XI. LAUNCHING OF XENOGENEIC HUMAN CLINICAL TRIALS IN THE UNITED STATES USING IMMUNOMODULATION396
XII. COMMENT396
XIII. REFERENCES397
Chapter Twenty-Eight: Immunoisolation399
I. INTRODUCTION399
II. THEORY AND CAPSULE FORMAT399
III. CELL SOURCING401
IV. HOST IMMUNE RESPONSES TO ENCAPSULATED CELLS401
V. CONCLUSION402
VI. REFERENCES403
Chapter Twenty-Nine: Engineering Challenges in Immunobarrier Device Development405
I. INTRODUCTION405
II. ENGINEERING CHALLENGES406
III. STRATEGIES FOR IMPROVING IMMUNOBARRIER DEVICES410
IV. THEORETICAL ANALYSIS OF PFC-CONTAINING MICROCAPSULES411
V. FUTURE DIRECTIONS416
VI. REFERENCES416
Part Seven: Stem Cells419
Chapter Thirty: Embryonic Stem Cells421
I. INTRODUCTION421
II. DERIVATION OF HUMAN EMBRYONIC STEM CELLS (hESC)422
III. SELECTING EMBRYOS FOR PRODUCING EMBRYONIC STEM CELLS422
IV. MAINTAINING EMBRYONIC STEM CELLS423
V. PLURIPOTENTIAL MARKERS OF EMBRYONIC STEM CELLS423
VI. GENETIC MANIPULATION OF EMBRYONIC STEM CELLS424
VII. DIFFERENTIATION OF EMBRYONIC STEM CELLS424
VIII. DIRECTING DIFFERENTIATION OF EMBRYONIC STEM CELLS425
IX. COCULTURE SYSTEMS FOR DIRECTED DIFFERENTIATION OF EMBRYONIC STEM CELLS425
X. CONCLUDING COMMENTS426
XI. REFERENCES426
Chapter Thirty-One: Adult Epithelial Tissue Stem Cells431
I. INTRODUCTION431
II. A DEFINITION OF STEM CELLS432
III. HIERARCHICALLY ORGANIZED STEM CELL POPULATIONS433
IV. SKIN STEM CELLS435
V. INTESTINAL STEM CELL SYSTEM437
VI. STEM CELL ORGANIZATION IN FILIFORM PAPILLAE ON THE DORSAL SURFACE OF THE TONGUE441
VII. GENERALIZED SCHEME441
VIII. ADULT STEM CELL PLASTICITY442
IX. REFERENCES443
Chapter Thirty-Two: Embryonic Stem Cells as a Cell Source for Tissue Engineering445
I. INTRODUCTION445
II. MAINTENANCE OF ESCS446
III. DIRECTED DIFFERENTIATION448
IV. ISOLATION OF SPECIFIC PROGENITOR CELLS FROM ESCs451
V. TRANSPLANTATION452
VI. FUTURE PROSPECTS454
VII. CONCLUSIONS454
VIII. ACKNOWLEDGMENTS455
IX. REFERENCES455
Chapter Thirty-Three: Postnatal Stem Cells459
I. INTRODUCTION459
II. RESERVOIRS OF POSTNATAL STEM CELLS459
III. CURRENT APPROACHES TO TISSUE ENGINEERING460
IV. CONCLUSIONS465
V. ACKNOWLEDGMENTS466
VI. REFERENCES466
Part Eight: Gene Therapy469
Chapter Thirty-Four: Gene Therapy471
I. INTRODUCTION471
II. STRATEGIES OF GENE THERAPY472
III. EX VIVO VS. IN VIVO GENE THERAPY472
IV. CHROMOSOMAL VS. EXTRACHROMOSOMAL PLACEMENT OF THE TRANSFERRED GENE473
V. GENE TRANSFER VECTORS474
VI. CELL-SPECIFIC TARGETING STRATEGIES480
VII. REGULATED EXPRESSION OF THE TRANSFERRED GENE483
VIII. COMBINING GENE TRANSFER WITH STEM CELL STRATEGIES485
IX. CHALLENGES TO GENE THERAPY FOR TISSUE ENGINEERING487
X. ACKNOWLEDGMENTS487
XI. REFERENCES487
Chapter Thirty-Five: Gene Delivery into Cells and Tissues493
I. INTRODUCTION493
II. GENE DELIVERY SYSTEMS493
III. EXPLORING THE ROLE OF RECEPTOR LIGAND SIGNALING AND RECEPTOR CLUSTERING IN AGENT DELIVERY495
IV. OVERVIEW OF NANOVEHICLE UPTAKE AND TRAFFICKING497
V. STABILITY OF NANOVECTORS IN BUFFERS AND BIOLOGICAL FLUIDS: STERIC VS. ELECTROSTATIC STABILIZATION500
VI. LOCALIZATION AND TARGETING501
VII. DRUG LOADING503
VIII. GENE DELIVERY SYSTEMS (GDS)504
IX. SPECIAL CONSIDERATIONS FOR GENE DELIVERY SYSTEMS507
X. OUTLOOK509
XI. ACKNOWLEDGMENT510
XII. REFERENCES510
Part Nine: Breast517
Chapter Thirty-Six: Breast Reconstruction519
I. INTRODUCTION519
II. CELL TYPES FOR SOFT-TISSUE ENGINEERING521
III. MATERIALS522
IV. ANIMAL MODELS526
V. STRATEGIES TO ENHANCE THE VASCULARIZATION OF ENGINEERED TISSUE528
VI. SPECIAL CONSIDERATIONS530
VII. CONCLUDING REMARKS530
VIII. REFERENCES531
Part Ten: Cardiovascular System535
Chapter Thirty-Seven: Progenitor Cells and Cardiac Homeostasis537
I. INTRODUCTION537
II. ORGAN HOMEOSTASIS537
III. CARDIAC HOMEOSTASIS539
IV. PROPERTIES OF EXOGENOUS AND ENDOGENOUS CELLS FOR CARDIAC REPAIR541
V. THE EMBRYO AS A MODEL OF PROGENITOR CELL ENGRAFTMENT AND PLASTICITY545
VI. CONCLUSIONS547
VII. REFERENCES547
Chapter Thirty-Eight: Cardiac-Tissue Engineering551
I. INTRODUCTION551
II. CLINICAL PROBLEM551
III. PROBLEM DEFINITION552
IV. PREVIOUS WORK554
V. BIOMIMETIC APPROACH TO CARDIAC-TISSUE ENGINEERING554
VI. ENGINEERED HEART TISSUE BY MECHANICAL STIMULATION OF CELLS IN COLLAGEN GELS560
VII. CELL-SHEET TISSUE ENGINEERING563
VIII. SUMMARY AND CURRENT RESEARCH NEEDS563
IX. ACKNOWLEDGMENTS565
X. REFERENCES566
Chapter Thirty-Nine: Blood Vessels569
I. INTRODUCTION569
II. CURRENT STATUS OF VASCULAR CONDUITS570
III. PHYSICAL OR CHEMICAL MODIFICATION OF CURRENT GRAFTS TO IMPROVE DURABILITY572
IV. THERAPEUTIC ANGIOGENESIS AND ARTERIOGENESIS576
V. TISSUE-ENGINEERED VASCULAR GRAFTS577
VI. ENDOVASCULAR STENTS AND STENT GRAFTS581
VII. CONCLUSION582
VIII. REFERENCES582
Chapter Forty: Heart Valves585
I. INTRODUCTION585
II. HEART VALVE FUNCTION AND STRUCTURE585
III. CELLULAR BIOLOGY OF THE HEART VALVE586
IV. HEART VALVE DYSFUNCTION AND VALVULAR REPAIR AND REMODELING588
V. APPLICATION OF TISSUE ENGINEERING TOWARD THE CONSTRUCTION OF A REPLACEMENT HEART VALVE590
VI. CONCLUSION597
VII. REFERENCES597
Part Eleven: Endocrinology and Metabolism603
Chapter Forty-One: Generation of Islets from Stem Cells605
I. INTRODUCTION605
II. ISLET TRANSPLANTATION606
III. ALTERNATIVE SOURCES OF ISLET CELLS608
IV. BIOMATERIALS611
V. ACKNOWLEDGMENTS615
VI. REFERENCES616
Chapter Forty-Two: Bioartificial Pancreas619
I. INTRODUCTION619
II. CELL TYPES FOR PANCREATIC SUBSTITUTES620
III. CONSTRUCT TECHNOLOGY623
IV. IN VIVO IMPLANTATION626
V. CONCLUDING REMARKS629
VI. ACKNOWLEDGMENTS630
VII. REFERENCES630
Chapter Forty-Three: Engineering Pancreatic Beta-Cells635
I. INTRODUCTION635
II. ENGINEERING TO GENERATE INSULIN-PRODUCING CELLS636
III. ENGINEERING TO IMPROVE ISLET SURVIVAL640
IV. VECTORS FOR ENGINEERING ISLETS AND BETA-CELLS641
V. CONCLUSION643
VI. REFERENCES643
Chapter Forty-Four: Thymus and Parathyroid Organogenesis647
I. INTRODUTION647
II. STRUCTURE AND MORPHOLOGY OF THE THYMUS647
III. IN VITRO T-CELL DIFFERENTIATION649
IV. THYMUS ORGANOGENESIS650
V. SUMMARY658
VI. ACKNOWLEDGMENTS658
VII. REFERENCES658
Part Twelve: Gastrointestinal System663
Chapter Forty-Five: Adult Stem Cells in Normal Gastrointestinal Function and Inflammatory Disease665
I. INTRODUCTION665
II. DEFINING PROPERTIES OF ADULT STEM CELLS666
III. CELLS OF THE INTESTINE666
IV. IDENTIFICATION OF INTESTINAL STEM CELLS669
V. PATHWAYS OF CELLULAR DIFFERENTIATION IN THE INTESTINE670
VI. ADULT STEM CELL PLASTICITY672
VII. BONE MARROW CONTRIBUTION TO THE CELLS IN THE ADULT INTESTINE672
VIII. ORIGIN OF THE ISEMFS673
IX. BONE MARROW–DERIVED VASCULAR LINEAGES CONTRIBUTE TO TISSUE REGENERATION IN IBD674
X. STEM CELL PLASTICITY: DE NOVO CELL GENERATION OR HETEROKARYON FORMATION675
XI. BONE MARROW TRANSPLANTATION AS A POTENTIAL THERAPY FOR CROHN’S DISEASE676
XII. REFERENCES676
Chapter Forty-Six: Alimentary Tract681
I. INTRODUCTION681
II. TISSUE-ENGINEERED SMALL INTESTINE681
III. TISSUE-ENGINEERED ESOPHAGUS686
IV. TISSUE-ENGINEERED STOMACH689
V. TISSUE-ENGINEERED LARGE INTESTINE691
VI. CONCLUSIONS692
VII. REFERENCES692
Chapter Forty-Seven: Liver Stem Cells695
I. INTRODUCTION695
II. DEFINITION OF A TISSUE-DERIVED STEM CELL695
III. CELLULAR ORGANIZATION OF THE ADULT LIVER696
IV. HEPATOCYTES: THE FUNCTIONAL UNIT OF THE LIVER WITH STEM CELL PROPERTIES696
V. LIVER STEM CELLS699
VI. LIVER STEM CELLS AND THERAPEUTIC APPROACHES703
VII. CONCLUSION704
VIII. REFERENCES704
Chapter Forty-Eight: Liver707
I. INTRODUCTION707
II. LIVER FAILURE AND CURRENT TREATMENTS707
III. CELL SOURCES FOR LIVER CELL–BASED THERAPIES709
IV. IN VITRO HEPATIC CULTURE MODELS711
V. EXTRACORPOREAL BIOARTIFICIAL LIVER DEVICES717
VI. CELL TRANSPLANTATION721
VII. THREE-DIMENSIONAL HEPATOCELLULAR SYSTEMS: DEVELOPMENT OF IMPLANTABLE THERAPEUTIC CONSTRUCTS722
VIII. ANIMAL MODELS726
IX. CONCLUSION726
X. REFERENCES726
Part Thirteen: Hematopoietic System733
Chapter Forty-Nine: Hematopoietic Stem Cells735
I. INTRODUCTION735
II. HISTORICAL BACKGROUND735
III. PROPERTIES OF HEMATOPOIETIC STEM CELLS (HSC)736
IV. ONTOGENY OF HSC737
V. MIGRATION, MOBILIZATION, AND HOMING OF HSC738
VI. HSC PROLIFERATION AND EXPANSION IN VITRO739
VII. NEGATIVE REGULATION OF HSC744
VIII. HEMATOPOIETIC STEM CELL NICHES744
IX. CONCLUSION745
X. REFERENCES746
Chapter Fifty: Red Blood Cell Substitutes749
I. INTRODUCTION749
II. MODIFIED HEMOGLOBIN750
III. FIRST-GENERATION MODIFIED HEMOGLOBIN751
IV. NEW GENERATIONS OF MODIFIED HEMOGLOBIN753
V. A CHEMICAL APPROACH BASED ON PERFLUOROCHEMICALS755
VI. CONCLUSIONS755
VII. LINK TO WEBSITES756
VIII. ACKNOWLEDGMENTS756
IX. REFERENCES756
Chapter Fifty-One: Lymphoid Cells759
I. INTRODUCTION759
II. PROPERTIES OF LYMPHOCYTES760
III. LYMPHOCYTE ENGINEERING: REALITY AND POTENTIAL760
IV. INDUCTIVE MODEL OF SEQUENTIAL CELL COMMITMENT OF HEMATOPOIESIS760
V. DIAGRAMS TO EXPLAIN THIS MODEL761
VI. SOME COMMENTS ON THIS MODEL761
VII. CRITERIA FOR ENGINEERING DEVELOPMENTAL STAGES OF LYMPHOPOIESIS763
VIII. STAGES OF LYMPHOPOIESIS FOR ENGINEERING763
IX. CONCLUDING REMARKS AND PROSPECTS FOR LYMPHOCYTE ENGINEERING779
X. ACKNOWLEDGMENTS780
XI. REFERENCES780
Part Fourteen: Kidney and Genitourinary System785
Chapter Fifty-Two: Stem Cells in Kidney Development and Regeneration787
I. INTRODUCTION787
II. KIDNEY DEVELOPMENT787
III. GENES THAT SPECIFY EARLY KIDNEY CELL LINEAGES789
IV. ESTABLISHMENT OF ADDITIONAL CELL LINEAGES792
V. REGENERATION AND RENAL STEM CELLS794
VI. ACKNOWLEDGMENTS797
VII. REFERENCES797
Chapter Fifty-Three: Renal Replacement Devices801
I. INTRODUCTION801
II. BASICS OF KIDNEY FUNCTION801
III. TISSUE-ENGINEERING APPROACH TO RENAL FUNCTION REPLACEMENT802
IV. REFERENCES809
Chapter Fifty-Four: Genitourinary System811
I. INTRODUCTION811
II. RECONSTITUTION STRATEGIES811
III. ROLE OF BIOMATERIALS812
IV. VASCULARIZATION812
V. PROGRESS IN TISSUE ENGINEERING OF UROLOGIC STRUCTURES812
VI. ADDITIONAL APPLICATIONS816
VII. CONCLUSION818
VIII. REFERENCES818
Part Fifteen: Musculoskeletal System821
Chapter Fifty-Five: Mesenchymal Stem Cells823
I. INTRODUCTION823
II. MSC BIOLOGY RELEVANT TO MUSCULOSKELETAL-TISSUE ENGINEERING823
III. MSCs IN MUSCULOSKELETAL TISSUE ENGINEERING829
IV. CONCLUSIONS AND FUTURE PERSPECTIVES838
V. ACKNOWLEDGMENT838
VI. REFERENCES838
Chapter Fifty-Six: Bone Regeneration845
I. INTRODUCTION845
II. CELL-BASED APPROACH TO BONE-TISSUE ENGINEERING846
III. GROWTH FACTOR–BASED THERAPIES853
IV. CONCLUSION AND FUTURE TRENDS857
V. REFERENCES857
Chapter Fifty-Seven: Bone and Cartilage Reconstruction861
I. INTRODUCTION861
II. BONE RECONSTRUCTION861
III. CLINICAL APPLICATION OF ENGINEERED BONE867
IV. CARTILAGE RECONSTRUCTION868
V. CONCLUSION873
VI. ACKNOWLEDGEMENTS874
VII. REFERENCES874
Chapter Fifty-Eight: Regeneration and Replacement of the Intervertebral Disc877
I. INTRODUCTION877
II. IVD STRUCTURE AND FUNCTION878
III. BIOMATERIALS FOR NUCLEUS PULPOSUS REPLACEMENT880
IV. CELL-BIOMATERIAL CONSTRUCTS FOR IVD REGENERATION882
V. CELLULAR ENGINEERING FOR INTERVERTEBRAL DISC REGENERATION886
VI. GROWTH FACTORS AND BIOLOGICS FOR INTERVERTEBRAL DISC REGENERATION889
VII. GENE THERAPY FOR INTERVERTEBRAL DISC REGENERATION889
VIII. CONCLUDING REMARKS891
IX. ACKNOWLEDGMENTS891
X. REFERENCES891
Chapter Fifty-Nine: Articular Cartilage Injury897
I. INTRODUCTION897
II. ARTICULAR-CARTILAGE INJURY AND JOINT DEGENERATION898
III. MECHANISMS OF ARTICULAR-CARTILAGE INJURIES898
IV. RESPONSE OF ARTICULAR CARTILAGE TO INJURY900
V. PREVENTING JOINT DEGENERATION FOLLOWING INJURY902
VI. PROMOTING ARTICULAR SURFACE REPAIR902
VII. CONCLUSION904
VIII. REFERENCES904
Chapter Sixty: Tendons and Ligaments909
I. INTRODUCTION909
II. NEED FOR BIOENGINEERED TENDON AND LIGAMENT SUBSTITUTES910
III. HISTOLOGICAL DESCRIPTION OF TENDONS AND LIGAMENTS910
IV. TISSUE-ENGINEERED ACL SUBSTITUTES911
V. CONCLUSION915
VI. ACKNOWLEDGMENTS916
VII. REFERENCES916
Chapter Sixty-One: Mechanosensory Mechanisms in Bone919
I. INTRODUCTION919
II. THE CONNECTED CELLULAR NETWORK (CCN)920
III. MECHANOSENSATION ON THE CCN921
IV. MESENCHYMAL STEM CELLS927
V. ACKNOWLEDGMENTS928
VI. REFERENCES928
Chapter Sixty-Two: Skeletal-Tissue Engineering935
I. INTRODUCTION935
II. DISTRACTION OSTEOGENESIS936
III. CRITICAL-SIZED DEFECTS937
IV. CELLULAR THERAPY937
V. CYTOKINES938
VI. SCAFFOLDS940
VII. ANGIOGENESIS940
VIII. TISSUE ENGINEERING IN PRACTICE941
IX. CONCLUSION942
X. REFERENCES942
Part Sixteen: Nervous System945
Chapter Sixty-Three: Neural Stem Cells947
I. INTRODUCTION947
II. NEURAL DEVELOPMENT947
III. NEURAL STEM CELLS948
IV. EMBRYONIC STEM CELL–DERIVED NEURAL STEM CELLS AND NEURAL PROGENY951
V. APPLICATIONS IN BIOLOGY AND DISEASE955
VI. CONCLUSION958
VII. REFERENCES958
Chapter Sixty-Four: Brain Implants967
I. INTRODUCTION967
II. CELL REPLACEMENT IMPLANTS968
III. CELL PROTECTION AND REGENERATION IMPLANTS970
IV. COMBINED REPLACEMENT AND REGENERATION IMPLANTS973
V. DISEASE TARGETS FOR BRAIN IMPLANTS974
VI. SURGICAL CONSIDERATIONS975
VII. CONCLUSIONS975
VIII. REFERENCES975
Chapter Sixty-Five: Spinal Cord977
I. INTRODUCTION977
II. THE PROBLEM977
III. SPINAL CORD ORGANIZATION978
IV. INJURY978
V. SPONTANEOUS REGENERATION979
VI. CURRENT LIMITATIONS AND APPROACHES TO REPAIR AND REDEFINING GOALS979
VII. SPINAL CORD DEVELOPMENT980
VIII. EMBRYONIC STEM CELLS981
IX. NOVEL APPROACHES TO CNS REPAIR986
X. TOWARD HUMAN TRIALS989
XI. CONCLUSIONS990
XII. ACKNOWLEDGMENTS991
XIII. REFERENCES991
Chapter Sixty-Six: Protection and Repair of Audition995
I. INTRODUCTION995
II. INTERVENTIONS TO PREVENT HEARING LOSS/COCHLEAR DAMAGE996
III. HAIR CELL REGENERATION998
IV. AUDITORY NERVE SURVIVAL FOLLOWING DEAFNESS999
V. GENETIC DEAFNESS1000
VI. METHODS OF THERAPEUTIC INTERVENTION1000
VII. CONCLUSIONS1002
VIII. REFERENCES1003
Part Seventeen: Ophthalmic Applications1009
Chapter Sixty-Seven: Stem Cells in the Eye1011
I. INTRODUCTION1011
II. CORNEAL EPITHELIAL STEM CELLS1011
III. RETINAL PROGENITOR CELLS1017
IV. BONE MARROW STEM CELLS1017
V. POTENTIAL FOR STEM CELLS IN OCULAR REPAIR AND TISSUE ENGINEERING1018
VI. REFERENCES1018
Chapter Sixty-Eight: Corneal-Tissue Replacement1025
I. INTRODUCTION1025
II. SYNTHETIC CORNEAL REPLACEMENTS1029
III. CORNEAL-TISSUE ENGINEERING1031
IV. CURRENT STATE OF CORNEAL-TISSUE ENGINEERING AND FUTURE DIRECTIONS1043
V. REFERENCES1043
Chapter Sixty-Nine: Vision Enhancement Systems1049
I. INTRODUCTION1049
II. VISUAL SYSTEM, ARCHITECTURE, AND (DYS)FUNCTION1049
III. CURRENT AND NEAR-TERM APPROACHES TO VISION RESTORATION1052
IV. EMERGING APPLICATION AREAS FOR ENGINEERED CELLS AND TISSUES1058
V. CONCLUSION: TOWARD 20/20 VISION1061
VI. ACKNOWLEDGMENTS1061
VII. REFERENCES1061
Part Eighteen: Oral/Dental Applications1065
Chapter Seventy: Biological Tooth Replacement and Repair1067
I. INTRODUCTION1067
II. TOOTH DEVELOPMENT1067
III. WHOLE TOOTH-TISSUE ENGINEERING1068
IV. DENTAL-TISSUE REGENERATION1071
V. CONCLUSIONS1075
VI. REFERENCES1075
Chapter Seventy-One: Oral and Maxillofacial Surgery1079
I. INTRODUCTION1079
II. SPECIAL CHALLENGES IN ORAL AND MAXILLOFACIAL RECONSTRUCTION1079
III. CURRENT METHODS OF ORAL AND MAXILLOFACIAL RECONSTRUCTION1082
IV. RELEVANT STRATEGIES IN ORAL- AND MAXILLOFACIAL-TISSUE ENGINEERING1085
V. FUTURE OF ORAL- AND MAXILLOFACIAL-TISSUE ENGINEERING1091
VI. REFERENCES1091
Chapter Seventy-Two: Periodontal-Tissue Engineering1095
I. INTRODUCTION1095
II. FACTORS FOR PERIODONTAL TISSUE ENGINEERING AND REGENERATIVE MEDICINE1097
III. CURRENT APPROACHES IN PERIODONTAL TISSUE ENGINEERING1099
IV. FUTURE DIRECTIONS1104
V. ACKNOWLEDGMENTS1105
VI. REFERENCES1105
Part Nineteen: Respiratory System1111
Chapter Seventy-Three: Progenitor Cells in the Respiratory System1113
I. INTRODUCTION: LUNG BIOLOGY AND OPPORTUNITIES FOR REGENERATION OF THE LUNG1113
II. COMPLEXITY OF LUNG STRUCTURE PRESENTS A CHALLENGE FOR TISSUE ENGINEERING1113
III. LUNG MORPHOGENESIS1114
IV. ENDOGENOUS PROGENITOR CELLS PLAY CRITICAL ROLES IN REPAIR OF THE RESPIRATORY EPITHELIUM AFTER BI1118
V. EVIDENCE FOR NONPULMONARY STEM CELLS IN THE LUNG1120
VI. MODELS FOR STUDY OF LUNG REGENERATION IN VITRO1121
VII. SUMMARY AND CONCLUSIONS1121
VIII. REFERENCES1122
Chapter Seventy-Four: Lungs1125
I. INTRODUCTION1125
II. LUNG STRUCTURE1126
III. CELL SOURCES FOR LUNG REPAIR AND LUNG-TISSUE ENGINEERING1126
IV. LUNG-TISSUE CONSTRUCTS1129
V. CONCLUSIONS1130
VI. REFERENCES1131
Part Twenty: Skin1135
Chapter Seventy-Five: Cutaneous Stem Cells1137
I. INTRODUCTION1137
II. WHAT ARE EPITHELIAL STEM CELLS?1138
III. LOCALIZATION OF EPITHELIAL STEM CELLS1138
IV. IN VITRO ASSESSMENT OF PROLIFERATIVE POTENTIAL1140
V. MULTIPOTENT BULGE CELLS?1142
VI. PLASTICITY OF BULGE CELLS?1143
VII. BULGE CELLS: THE ULTIMATE CUTANEOUS EPITHELIAL STEM CELLS?1143
VIII. ROLE OF BULGE CELLS IN WOUND HEALING1143
IX. ROLE OF BULGE CELLS IN TUMORIGENESIS1144
X. STEM CELLS AND ALOPECIA1144
XI. BULGE CELLS FOR TISSUE ENGINEERING1144
XII. MOLECULAR PROFILE „ STEM CELL PHENOTYPE1145
XIII. THE BULGE AS STEM CELL NICHE1145
XIV. CONCLUSION1145
XV. ACKNOWLEDGMENTS1146
XVI. REFERENCES1146
Chapter Seventy-Six: Wound Repair1149
I. INTRODUCTION1149
II. BASIC BIOLOGY OF WOUND REPAIR1150
III. CHRONIC WOUNDS1157
IV. TISSUE-ENGINEERED THERAPY: ESTABLISHED PRACTICE1157
V. TISSUE-ENGINEERED THERAPY: NEW APPROACHES1159
VI. REFERENCES1161
Chapter Seventy-Seven: Bioengineered Skin Constructs1167
I. INTRODUCTION1167
II. SKIN STRUCTURE AND FUNCTION1168
III. ENGINEERING SKIN TISSUE1172
IV. EPIDERMAL REGENERATION1174
V. DERMAL REPLACEMENT1174
VI. COMPOSITE SKIN GRAFTS1175
VII. BIOENGINEERED SKIN: FDA-APPROVED INDICATIONS1176
VIII. MECHANISMS OF ACTION OF BIOENGINEERED SKIN1179
IX. CONCLUSION1182
X. REFERENCES1182
Part Twenty-One: Clinical Experience1187
Chapter Seventy-Eight: Current State of Clinical Application1189
I. INTRODUCTION1189
II. CURRENT CHALLENGES1189
III. CLINICAL APPLICATIONS1190
IV. CONCLUSION1198
V. REFERENCES1199
Chapter Seventy-Nine: Tissue-Engineered Skin Products1201
I. INTRODUCTION1201
II. TYPES OF THERAPEUTIC TISSUE-ENGINEERED SKIN PRODUCTS1202
III. COMPONENTS OF TISSUE-ENGINEERED SKIN GRAFTS AS RELATED TO FUNCTION1203
IV. COMMERCIAL PRODUCTION OF TISSUE-ENGINEERED SKIN PRODUCTS1204
V. MANUFACTURE OF DERMAGRAFT AND TRANSCYTE1206
VI. DERMAGRAFT AND TRANSCYTE PRODUCTION PROCESSES1207
VII. CLINICAL TRIALS1209
VIII. IMMUNOLOGICAL PROPERTIES OF TISSUE-ENGINEERED SKIN1210
IX. COMMERCIALIZATION1210
X. FUTURE DEVELOPMENTS1211
XI. CONCLUSION1212
XII. REFERENCES1212
Chapter Eighty: Tissue-Engineered Cartilage Products1215
I. INTRODUCTION1215
II. CLINICAL EXPERIENCE WITH FIRST-GENERATION ACI1217
III. CLINICAL EXPERIENCE WITH SECOND-GENERATION ACI1221
IV. CONCLUSIONS1222
V. REFERENCES1222
Chapter Eighty-One: Tissue-Engineered Bone Products1225
I. INTRODUCTION1225
II. BONE HEALING1226
III. OSTEOGENIC GRAFTING MATERIALS1226
IV. OSTEOCONDUCTIVE BONE GRAFT MATERIALS1228
V. OSTEOINDUCTIVE BONE GRAFT MATERIALS1229
VI. COMPOSITE BONE GRAFTING1232
VII. REGULATORY ISSUES1232
VIII. EXAMPLES OF TISSUE ENGINEERING IN CONTEMPORARY CLINICAL ORTHOPEDICS1233
IX. THE FUTURE1233
X. CONCLUSIONS1235
XI. ACKNOWLEDGMENTS1235
XII. REFERENCES1235
Chapter Eighty-Two: Tissue-Engineered Cardiovascular Products1237
I. INTRODUCTION1237
II. CLINICAL NEED FOR TISSUE-ENGINEERED CARDIOVASCULAR PRODUCTS?1238
III. REQUIREMENTS FOR CLINICAL APPLICATION1239
IV. CURRENT CONCEPTS AND ACHIEVEMENTS IN ENGINEERING CARDIOVASCULAR PRODUCTS1241
V. STATE OF MYOCARDIAL-TISSUE ENGINEERING1243
VI. BOTTLENECKS1246
VII. SUMMARY1247
VIII. REFERENCES1248
Chapter Eighty-Three: Tissue-Engineered Organs1253
I. INTRODUCTION1253
II. TISSUE ENGINEERING: STRATEGIES FOR TISSUE RECONSTITUTION1253
III. CELL SOURCES1254
IV. ALTERNATE CELL SOURCES1254
V. THERAPEUTIC CLONING1255
VI. BIOMATERIALS1256
VII. GROWTH FACTORS1257
VIII. VASCULARIZATION1257
IX. CLINICAL APPLICATIONS1257
X. CONCLUSION1259
XI. REFERENCES1259
Part Twenty-Two: Regulation and Ethics1263
Chapter Eighty-Four: The Tissue-Engineering Industry1265
I. INTRODUCTION1265
II. THE AGE OF INNOCENCE1266
III. THE PERFECT STORM1267
IV. THE PRESENT ERA1268
V. CONCLUDING PERSPECTIVES1270
VI. REFERENCES1270
Chapter Eighty-Five: The Regulatory Path From Concept to Market1271
I. INTRODUCTION1271
II. LEGISLATIVE AUTHORITY1272
III. PRODUCT REGULATORY PROCESS1272
IV. PRODUCT PREMARKET SUBMISSIONS1273
V. REVIEW OF PRODUCT PREMARKET SUBMISSIONS1275
VI. HUMAN CELLS, TISSUES, AND CELLULAR- AND TISSUE-BASED PRODUCTS1275
VII. SCIENCE AND PRODUCT DEVELOPMENT1277
VIII. CONCLUSION AND FUTURE PERSPECTIVES1278
IX. ACKNOWLEDGMENTS1279
X. REFERENCES1279
Chapter Eighty-Six: Ethical Issues1281
I. INTRODUCTION1281
II. ARE THERE REASONS, IN PRINCIPLE, WHY PERFORMING THE BASIC RESEARCH SHOULD BE IMPERMISSIBLE?1282
III. WHAT CONTEXTUAL FACTORS SHOULD BE TAKEN INTO ACCOUNT, AND DO ANY OF THESE PREVENT THE DEVELOPME1284
IV. WHAT PURPOSES, TECHNIQUES, OR APPLICATIONS WOULD BE PERMISSIBLE AND UNDER WHAT CIRCUMSTANCES?1285
V. ON WHAT PROCEDURES AND STRUCTURES, INVOLVING WHAT POLICIES, SHOULD DECISIONS ON APPROPRIATE TECHN1285
VI. CONCLUSION1286
VII. REFERENCES1286
Epilogue1289
INDEX1291

Book details

Vendor Elsevier S & T
SKU 9780123706157
ISBN-13 9780080548845
Author Lanza, Robert; Langer, Robert; Vacanti, Joseph P.
Edition 3rd
Category Medical
Subject Physiology

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First published in 1997, Principles of Tissue Engineering is the widely recognized definitive resource in the field. The third edition provides a much needed update of the rapid progress that has been achieved in the field, combining the prerequisites for a general understanding of tissue growth and development, the tools and theoretical information needed to design tissues and organs, as well as a presentation by the world’s experts of what is currently known about each specific organ system.
This edition includes greatly expanded focus on stem cells, including adult and embryonic stem cells and progenitor populations that may soon lead to new tissue engineering therapies for heart disease, diabetes, and a wide variety of other diseases that afflict humanity. This up-to-date coverage of stem cell biology and other emerging technologies is complemented by a series of new chapters on recent clinical experience in applying tissue engineering. The result is a comprehensive textbook that we believe will be useful to students and experts alike.

New to this edition:
*Includes new chapters on biomaterial-protein interactions, nanocomposite and three-dimensional scaffolds, skin substitutes, spinal cord, vision enhancement, and heart valves
*Expanded coverage of adult and embryonic stem cells of the cardiovascular, hematopoietic, musculoskeletal, nervous, and other organ systems

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