اصول پزشکی ترمیمی

Front Cover ......Page 1 PRINCIPLES OF REGENERATIVE MEDICINE......Page 2 PRINCIPLES OF REGENERATIVE MEDICINE......Page 4 Copyright......Page 5 Dedication......Page 6 Contents......Page 8 Contributors......Page 20 Preface......Page 26 MOLECULES THAT ORGANIZE CELLS......Page 28 Changes in Cell–Cell Adhesion......Page 29 Invasion of the Basal Lamina......Page 30 Transcription Factors That Regulate Epithelial–Mesenchymal Transition......Page 31 MOLECULAR CONTROL OF THE EPITHELIAL–MESENCHYMAL TRANSITION......Page 32 Wnt Pathway......Page 33 Additional Signaling Pathways......Page 34 CONCLUSION......Page 35 References......Page 36 COMPOSITION AND DIVERSITY OF THE EXTRACELLULAR MATRIX......Page 42 RECEPTORS FOR EXTRACELLULAR MATRIX MOLECULES......Page 43 SIGNAL TRANSDUCTION EVENTS DURING CELL–EXTRACELLULAR MATRIX INTERACTIONS......Page 45 Adhesion and Migration......Page 46 Proliferation and Survival......Page 49 Differentiation......Page 50 Apoptosis......Page 51 Adhesion and Migration......Page 52 Differentiation......Page 54 CELL–EXTRACELLULAR MATRIX INTERACTIONS DURING REGENERATIVE FETAL WOUND HEALING......Page 55 Proliferation......Page 56 IMPLICATIONS FOR REGENERATIVE MEDICINE......Page 57 References......Page 58 BLASTEMA FORMATION......Page 64 Hemostasis and Reepithelialization......Page 65 Mechanisms of Dedifferentiation......Page 66 Cell Cycling During Blastema Formation......Page 67 Blastema Cell Migration and Accumulation......Page 68 The Apical Epidermal Cap–Nerve Interaction......Page 69 Interaction of Cells From Opposite Sides of the Limb Circumference......Page 71 References......Page 72 GROUND STATE AND PRIMED EMBRYONIC STEM CELLS HAVE UNIQUE SIGNALING NETWORKS UNDERLYING PLURIPOTENCY......Page 76 LEUKEMIA INHIBITORY FACTOR AND BONE MORPHOGENIC PROTEIN SIGNALING PATHWAYS REGULATE MOUSE EMBRYONIC STEM CELL SELF-RENEWAL......Page 77 WNT SIGNALING CONTRIBUTES TO MAINTENANCE OF PLURIPOTENCY IN MOUSE EMBRYONIC STEM CELLS AND TO THE NAIVE HUMAN EMBRYONIC STE .........Page 79 THREE TRANSCRIPTION FACTORS, OCTAMER BINDING PROTEIN 4, SRY-BOX 2, AND NANOG, FORM THE CORE PLURIPOTENCY TRANSCRIPTIONAL NE .........Page 80 MYC LINKS CELL SIGNALING TO PLURIPOTENCY GENE REGULATION......Page 81 A SPECIFIC EPIGENETIC PROGRAM HELPS MAINTAIN PLURIPOTENCY......Page 82 MICRORNAS INTEGRATE WITH CELL SIGNALING AND TRANSCRIPTION FACTORS TO REGULATE STEM CELL PROLIFERATION AND DIFFERENTIATION......Page 84 CONCLUSIONS......Page 85 References......Page 86 INTRODUCTION......Page 92 Adult Wound Healing and Scar Formation......Page 93 Fibroproliferative Scarring......Page 95 Hypertrophic Scars......Page 97 Fetal Scarless Wound Repair......Page 99 Targeting the Inflammatory Response......Page 100 Connective Tissue Growth Factor......Page 102 Wingless Type Signaling......Page 103 5-Fluorouracil......Page 104 Bleomycin......Page 105 Cryotherapy......Page 106 Growth Factors and Cell Signaling Molecules......Page 107 Embryonic Stem Cells......Page 108 Mesenchymal Stem Cells......Page 109 Epidermal Stem Cells......Page 110 Induced Pluripotent Stem Cells......Page 111 PERSPECTIVE......Page 112 References......Page 113 INTRODUCTION......Page 120 SINGLE-CELL ISOLATION......Page 122 ACQUIRING SINGLE-CELL DATA......Page 123 Single-Cell Transcriptomics......Page 124 Single-Cell Proteomics......Page 126 Reducing Noise in Single-Cell Data......Page 127 Mathematical Identification of Cellular Subpopulations......Page 128 DETERMINING SUBPOPULATIONS......Page 130 Development of Cell-Based Therapies......Page 131 CLINICAL IMPLICATIONS OF CELLULAR HETEROGENEITY IN TISSUE REPAIR AND DISEASE......Page 132 Cellular Heterogeneity in Wound Healing......Page 133 Cellular Heterogeneity in Aging......Page 134 CONCLUSIONS......Page 135 References......Page 136 Mouse Embryonic Stem Cells......Page 140 Blastocyst......Page 141 Parthenogenesis......Page 142 Microenvironment......Page 143 Maintenance......Page 144 Evolution of Human Embryonic Stem Cell Derivation and Culture Methods......Page 145 HUMAN EMBRYONIC STEM CELL DIFFERENTIATION AND MANUFACTURING FOR CLINICAL APPLICATION......Page 146 References......Page 147 Further Reading......Page 150 INTRODUCTION......Page 152 Single Blastomere Biopsy......Page 153 Irreversibility as a Criterion for Diagnosing Embryonic Death......Page 154 Morphological Criteria for Predicting the Capacity of Irreversibly Arrested, Nonviable Human Embryos to Develop Into a Huma .........Page 155 References......Page 157 PLACENTA: FUNCTION, ORIGIN, AND COMPOSITION......Page 160 AMNIOTIC EPITHELIAL CELLS......Page 161 AMNIOTIC MESENCHYMAL STEM CELLS......Page 162 Preclinical Studies......Page 163 Characterization......Page 165 Preclinical Studies......Page 167 Heart......Page 168 Kidney......Page 169 Intestine......Page 170 References......Page 171 A BRIEF HISTORY......Page 176 PUBLIC VERSUS FAMILY (OR PRIVATE) BANKS......Page 177 Donor Recruitment and Consent......Page 178 Volume and Cell Count Considerations......Page 179 Processing and Cryopreservation......Page 180 Cord Blood Unit Characterization......Page 181 Cord Blood Transplantation for Nonmalignant Hematological Diseases......Page 183 Cord Blood Transplantation for Inherited Metabolic Disorders......Page 184 Cerebral Palsy......Page 186 Stroke......Page 187 Autism Spectrum Disorder......Page 188 References......Page 189 MECHANISMS OF REPROGRAMMING......Page 196 REPROGRAMMING TECHNIQUES......Page 197 INDUCED TRANSDIFFERENTIATION......Page 198 DISEASE MODELING......Page 199 PERSONALIZED MEDICINE......Page 201 CELL THERAPY......Page 202 CONCLUSIONS AND FUTURE DIRECTIONS......Page 203 References......Page 204 ADULT STEM CELLS......Page 208 ISOLATION OF RODENT MULTIPOTENT ADULT PROGENITOR CELL......Page 209 Hematopoietic Reconstitution With Multipotent Adult Progenitor Cells......Page 210 Effect of Multipotent Adult Progenitor Cells on Graft Versus Host Disease......Page 211 Multipotent Adult Progenitor Cell Immunodulatory and/or Trophic Effects in Ischemic Disease......Page 212 Possible Mechanisms of Trophic Effects: Secreted Proteome of Multipotent Adult Progenitor Cells......Page 213 References......Page 214 HEMATOPOIETIC STEM CELL PROPERTIES......Page 218 Fetal Liver Hematopoiesis......Page 219 In Vitro Hematopoiesis......Page 220 Phenotypic Properties of Hematopoietic Stem Cells......Page 221 Bone Marrow Transplantation......Page 222 Autologous Peripheral Blood Stem Cell Transplantation......Page 223 Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency......Page 224 Hematopoietic Stem Cell Transplantation for Tolerance Induction......Page 225 List of Acronyms and Abbreviations......Page 226 References......Page 227 INTRODUCTORY OVERVIEW......Page 232 THE STEM CELL NATURE OF MESENCHYMAL STEM CELLS......Page 233 WHICH TISSUES CONTAIN MESENCHYMAL STEM CELLS?......Page 234 MESENCHYMAL STEM CELL EXOSOMES......Page 235 IMMUNOMODULATORY EFFECTS OF MESENCHYMAL STEM CELLS......Page 238 INDUCED PLURIPOTENT STEM CELL–DERIVED MESENCHYMAL STEM CELLS......Page 239 Acknowledgments......Page 240 References......Page 241 INTRODUCTION AND HISTORY......Page 246 NEW INSIGHT......Page 247 Clinically Relevant Therapies Using Mesenchymal Stem Cells......Page 249 Diabetes......Page 250 THE NEW MESENCHYMAL STEM CELLS......Page 251 References......Page 252 INTRODUCTION......Page 256 Integration of Hepatocytes After Transplantation......Page 258 CLINICAL HEPATOCYTE TRANSPLANTATION......Page 259 Hepatocyte Transplantation in Acute Liver Failure......Page 260 Hepatocyte Transplantation for Metabolic Liver Disease......Page 261 Hepatocyte Transplants for Non–Organ Transplant Candidates......Page 264 Methods to Improve Engraftment and Repopulation......Page 265 Stem Cells and Alternative Cell Sources for Liver Therapy......Page 266 SUMMARY......Page 268 References......Page 269 DEVELOPMENT OF THE HEART FROM CARDIAC STEM/PROGENITOR CELLS......Page 274 c-Kit+ Cardiac Progenitor/Stem Cells......Page 275 Cardiac Neural Crest–Derived Progenitors......Page 277 Epicardial Progenitor Cells......Page 278 CELL-BASED THERAPEUTICS FOR HEART DISEASE......Page 279 MECHANISMS OF ACTION......Page 281 Pluripotent Stem Cells......Page 282 Adult Stem Cells......Page 283 Endothelial Progenitor Cells......Page 284 Mesenchymal Stem Cells......Page 285 Cardiac Stem Cells......Page 288 Other Cardiac Stem Cells......Page 290 COMBINED STEM CELL THERAPEUTICS......Page 292 References......Page 294 INTRODUCTION......Page 300 THE MOLECULAR CHARACTERISTICS OF MUSCLE STEM CELLS DURING MYOGENESIS IN REGENERATION......Page 301 FUNCTIONAL CHARACTERISTICS OF MUSCLE STEM CELLS......Page 303 ISOLATION OF MUSCLE STEM CELLS......Page 304 TRACKING MUSCLE STEM CELL BEHAVIOR THROUGH LIVE IMAGING (BIOLUMINESCENCE IMAGING AND INTRAVITAL IMAGING)......Page 305 Extracellular Matrix Components......Page 306 Biophysical Cues......Page 307 SATELLITE CELL SELF-RENEWAL MECHANISMS......Page 308 MUSCLE STEM CELL–INTRINSIC DEFECTS IN AGING AND DISEASE......Page 310 CHALLENGES IN THE USE OF SATELLITE CELLS IN REGENERATIVE MEDICINE......Page 311 OTHER STEM CELL TYPES WITHIN MUSCLE......Page 312 Induced Pluripotent Stem–Derived Muscle Stem Cells......Page 313 References......Page 314 CELLULAR FRACTIONS......Page 322 Adipose-Derived Stromal Cell......Page 323 CLINICAL DELIVERY OF ADIPOSE-DERIVED CELLS......Page 324 ENGINEERED NEO-TISSUE......Page 327 Carcinogenesis and Tumorigenesis......Page 328 References......Page 329 TYPES AND SOURCE OF STEM CELLS IN THE PERIPHERAL BLOOD......Page 334 Mobilization of Bone Marrow Cells......Page 335 Identification and Isolation of Endothelial Progenitor Cells......Page 338 In Vitro Expansion of Endothelial Progenitor Cells......Page 339 The Role of Endothelial Progenitor Cells in Physiological and Pathological Neovascularization......Page 340 Identification, Isolation, Characterization, and In Vitro Expansion......Page 342 Tissue Regeneration......Page 344 Tissue Engineering......Page 346 Mesenchymal Stem Cells......Page 347 The Use of Mesenchymal Stem/Marrow Stroma Cells for Gene Therapy......Page 349 CONCLUSIONS AND FUTURE DIRECTIONS......Page 352 References......Page 353 FROM ADULT PANCREATIC ISLETS TO STEM CELLS......Page 362 β CELLS FROM PLURIPOTENT STEM CELLS (EMBRYONIC STEM CELLS AND INDUCED PLURIPOTENT STEM CELLS)......Page 363 β CELLS FROM ADULT STEM/PROGENITOR CELLS OF THE BILIARY TREE AND PANCREAS......Page 368 MESENCHYMAL STEM CELLS TO MODULATE IMMUNITY AND PROMOTE TISSUE REPAIR IN DIABETES......Page 371 CONCLUSION......Page 372 References......Page 373 INTRODUCTION......Page 378 The Retina......Page 379 Retinitis Pigmentosa......Page 381 Human Embryonic Stem Cell–Derived Retinal Pigment Epithelium......Page 382 Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium......Page 383 Scaffolds for Retinal Pigment Epithelium Transplantation......Page 386 Photoreceptor Transplantation......Page 387 CELL-BASED NEUROPROTECTION......Page 388 DISEASE-IN-A-DISH MODELING FOR RETINAL DISORDERS......Page 389 Three-Dimensional Retinal Organoids......Page 390 CONCLUSION......Page 391 References......Page 392 Epidemiology......Page 396 Primary Versus Secondary Brain Injury......Page 397 Neuroinflammation......Page 398 Blood–Brain Barrier Permeability......Page 400 Cerebral Edema......Page 402 Mechanisms of Action......Page 403 Timing of Infusion......Page 404 Conventional Cell Delivery Routes, Continued......Page 405 Novel Cell Delivery Routes......Page 407 Reduction in Therapeutic Intensity: Pediatric Intensity Level of Therapy Scores......Page 408 Imaging Data......Page 409 Results......Page 410 Phase 1/2 Adipose-Derived Stem/Stromal Cells......Page 411 CONCLUSION......Page 412 Acknowledgments......Page 413 References......Page 414 INTRODUCTION......Page 418 Extracellular Matrix......Page 419 Ion Channels and Mechanoreceptors......Page 420 Cytoskeleton......Page 421 NUCLEUS AS THE CENTRAL ORGANELLE IN REGULATING MECHANOTRANSDUCTION......Page 423 CELLULAR MECHANOTRANSDUCTION MECHANISMS......Page 424 Mechanotransduction Through Cell–Cell Adhesions......Page 425 From Cells to Organs: How Mechanobiology Affects Tissue Development and Function......Page 426 CONCLUSIONS......Page 427 References......Page 428 INTRODUCTION......Page 432 BONE MORPHOGENETIC PROTEINS......Page 433 SCAFFOLDS OF EXTRACELLULAR MATRIX AND BIOMIMETIC BIOMATERIALS......Page 436 REGENERATIVE MEDICINE AND SURGERY OF ARTICULAR CARTILAGE......Page 439 REGENERATION OF ARTICULAR CARTILAGE SURFACE AND LUBRICATION......Page 440 References......Page 441 INTRODUCTION......Page 444 Strain......Page 445 Constitutive Relations......Page 448 Tissue Remodeling......Page 450 Mechanotransduction......Page 451 Mechanical Stimulation In Vivo......Page 454 Bone Bioreactors......Page 456 Blood Vessel Bioreactors......Page 458 CONCLUSIONS......Page 459 References......Page 460 CELL–EXTRACELLULAR MATRIX INTERACTIONS......Page 464 Effect of Physical Properties......Page 465 Stiffness and Compliance......Page 466 Surface Charge......Page 467 Methods of Altering Surface Chemistry......Page 468 Development of Bioactive Surfaces......Page 469 Cell Adhesion......Page 470 Cell Motility......Page 471 Cell Proliferation, Self-renewal, and Differentiation......Page 472 Fabrication Techniques......Page 473 Cellular Responses to Topographical Cues......Page 474 Electrically Conductive Substrate......Page 477 EFFECT OF DIMENSIONALITY......Page 478 Hydrogel Scaffolds......Page 479 Decellularized Tissue......Page 480 New Technology Development......Page 481 Cellular Responses to Three-Dimensional Substrates......Page 482 Cell Migration......Page 483 Effect of Externally Applied Mechanical Stimuli......Page 484 Mechanotransduction......Page 485 Cellular Responses in Modifying Extracellular Matrix......Page 486 CONCLUSION......Page 487 References......Page 488 Thermoresponsive Polymer for Biomedical Applications......Page 496 Controlled Grafting of Thermoresponsive Polymer on Culture Substrates......Page 497 Variety of Fabrication Techniques of Thermoresponsive Cell Culture Substrate......Page 498 Cornea Reconstruction......Page 499 Myocardium Regeneration......Page 500 Cell Sheet Layering Technique......Page 501 Vascularization in Cell Sheets for Large-scale Tissue Construction......Page 502 COMBINATION OF CELL SHEET ENGINEERING AND SCAFFOLD-BASED ENGINEERING......Page 504 Copatterning to Create a Cellular Microenvironment......Page 505 Intelligent Surfaces for Regulating Cell Orientation......Page 506 Skeletal Muscle Tissue Engineering......Page 507 CONCLUSIONS......Page 508 References......Page 509 INTRODUCTION......Page 512 Physical Properties......Page 513 Size......Page 514 Shape......Page 515 Surface Topography......Page 516 Optical Properties......Page 517 NANOBIOMATERIALS......Page 518 Bone Tissue......Page 520 Muscle Tissue......Page 521 Vascular Tissue......Page 522 Other Tissue......Page 523 Stem Cell Transfection......Page 524 Stem Cell Expansion......Page 525 References......Page 526 Mechanical Support......Page 532 Degradation Mechanisms......Page 534 Factors That Affect Degradation Rates......Page 535 Surface Modification for Degradation Control......Page 536 On-Demand Release......Page 537 Anisotropic and Gradient Scaffolds......Page 538 Surface Feature Manipulation......Page 539 SAFETY AND BIOCOMPATIBILITY REQUIREMENTS FOR BIOMATERIAL SCAFFOLDS......Page 540 Infection and Sterilization......Page 541 Hemocompatibility......Page 542 Foreign Body Response......Page 543 SUMMARY......Page 544 References......Page 545 WHY THE NEED FOR PRECISION CONTROL OF PROTEINS AT INTERFACES IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE?......Page 550 SURFACE ANALYSIS AND ITS ROLE IN THE PRECISION DELIVERY OF BIOLOGICAL SIGNALS......Page 551 Sum Frequency Generation......Page 552 Quartz Crystal Microbalance With Dissipation Monitoring......Page 553 TECHNIQUES AND TECHNOLOGIES FOR PRECISION IMMOBILIZATION AT SURFACES......Page 554 Ionic Charge and Charge Control of Orientation......Page 555 Collagen to Control Protein Orientation......Page 556 Streptavidin for Biomolecular Orientation Control......Page 557 CONCLUSIONS......Page 558 References......Page 559 INTRODUCTION......Page 562 Processing Methods......Page 565 COLLAGEN......Page 567 Processing Methods......Page 568 Collagen in Bone Tissue Engineering Applications......Page 569 Processing Methods......Page 570 Gellan Gum in Bone Tissue Engineering Applications......Page 571 Processing Methods......Page 572 Polyhydroxyalkanoates in Bone Tissue Engineering Applications......Page 573 Silk Fibroin in Bone Tissue Engineering Applications......Page 574 STARCH......Page 575 Processing Methods......Page 576 NATURAL-BASED BIOCERAMICS......Page 577 CALCIUM PHOSPHATES......Page 578 Calcium Phosphate in Bone Tissue Engineering Applications......Page 579 Silicate in Bone Tissue Engineering Applications......Page 580 CONCLUSIONS......Page 581 References......Page 582 INTRODUCTION......Page 586 POLYMER SYNTHESIS......Page 587 Poly(ethylene), Poly(propylene), and Poly(styrene)......Page 588 Poly(meth)acrylates and Polyacrylamides......Page 589 Poly(N-isopropylacrylamide)......Page 590 Polyethers......Page 591 Polysiloxanes......Page 592 Hydrolytically Stable Polyurethanes......Page 593 Polyesters......Page 594 Polyesters of α-Hydroxy Acids......Page 595 Polyesters of Lactones......Page 597 Polyorthoesters......Page 598 Polyurethanes......Page 599 Amino Acid–Derived Polymers, Poly(amino Acids), and Peptides......Page 600 Polyanhydrides......Page 601 Biodegradable Cross-linked Polymer Networks......Page 602 Cross-linked Polyesters......Page 603 CONCLUSION/SUMMARY......Page 607 References......Page 608 Calcium Phosphate Bioceramics......Page 618 Basic Properties......Page 620 Apatite Cements......Page 621 Setting/Hardening Mechanism......Page 622 Hydrolysis Interaction......Page 623 Setting Times......Page 624 Strategies to Improve Setting Times......Page 625 Strategies to Improve Injectability......Page 626 Liquid-to-Powder Ratio......Page 627 STRATEGIES TO IMPROVE THE MECHANICAL PROPERTIES......Page 628 Porosity......Page 629 Dual Setting System......Page 631 Mechanics of Fiber-Reinforced Calcium Phosphate Cements......Page 632 Oral, Maxillofacial, and Craniofacial Applications......Page 633 CONCLUSION......Page 634 References......Page 635 EXTRACELLULAR MATRIX: FUNCTION AND COMPONENTS......Page 640 Collagen......Page 642 Fibronectin......Page 643 Glycosaminoglycans/Proteoglycans......Page 644 Matrix-Bound Nanovesicles......Page 645 Decellularization......Page 646 Hydrogels......Page 647 Whole-Organ Scaffolds......Page 648 List of Acronyms and Abbreviations......Page 649 References......Page 650 INTRODUCTION......Page 654 BIOMATERIALS TEMPLATES......Page 655 STRUCTURE–PROPERTY RELATIONSHIPS IN HYDROGELS......Page 658 Bioactive Forms of Poly(ethylene Glycol) as Exemplars of Increasing Sophistication......Page 659 Spatial Heterogeneity......Page 660 Matrix Mechanics......Page 662 Hydrogel Degradation......Page 663 Polymerization Mechanisms......Page 664 Injectable Systems......Page 665 Hyaluronic Acid......Page 666 Alginate......Page 667 Cellulose......Page 668 Collagen and Its Derivatives......Page 669 Elastin Derivatives......Page 670 Fibrin Derivatives......Page 671 Self-assembled Peptides......Page 672 SYNTHETIC HYDROGELS FOR TISSUE ENGINEERING TEMPLATES......Page 673 CONCLUSIONS......Page 675 References......Page 676 Overview of Surface Modification Strategies......Page 678 Topographical Modifications......Page 680 Noncovalent Coatings......Page 682 BIOLOGICAL MODIFICATION OF SURFACES......Page 683 References......Page 686 TISSUE COMPONENTS......Page 688 REGENERATION OF DISEASED TISSUES......Page 689 Cell Sources......Page 690 Porosity......Page 691 Degradation......Page 693 Importance of Microvasculature......Page 694 Hydrogels......Page 696 CONCLUSIONS......Page 697 References......Page 698 INTRODUCTION......Page 702 Blood–Material Interactions and Initiation of the Inflammatory Response......Page 703 Provisional Matrix Formation......Page 704 Temporal Sequence of Inflammation and Wound Healing......Page 705 Chronic Inflammation......Page 706 Macrophage Interactions......Page 707 Foreign Body Giant Cell Formation and Interactions......Page 709 FIBROSIS AND FIBROUS ENCAPSULATION......Page 710 IMMUNOTOXICITY (ACQUIRED IMMUNITY)......Page 711 References......Page 718 Further Reading......Page 721 INTRODUCTION......Page 722 FUNCTIONS OF SCAFFOLDING AND EXTRACELLULAR MATRIX......Page 723 SCAFFOLDING APPROACHES IN BONE TISSUE ENGINEERING......Page 724 Hydrogels......Page 725 Silk......Page 726 Collagen......Page 727 Hyaluronic Acid......Page 728 Alginate......Page 729 Peptide Hydrogels......Page 730 Copolymers......Page 731 Ceramic Scaffolds......Page 732 Bioglass......Page 733 Metallic Scaffolds......Page 734 Polymer–Ceramics Blends......Page 735 Metal–Ceramic Blends......Page 736 References......Page 737 INTRODUCTION AND OVERVIEW OF CANCER IMMUNOTHERAPY......Page 742 ADVANTAGES AND DISADVANTAGES OF CANCER IMMUNOTHERAPY......Page 744 Introduction of Nanomedicine in Cancer......Page 745 Effects of Nanoparticle Surface Functionalization......Page 747 Nanoparticle Targeting of the Tumor Microenvironment......Page 748 Nanoparticle Targeting of Antigen Presenting Cells......Page 749 Implantable Biomaterial Scaffolds as Cancer Vaccines......Page 754 Injectable Biomaterial Systems as Cancer Vaccines......Page 756 Implantable Biomaterial Scaffolds to Enhance Autologous T Cell Therapy......Page 758 CONCLUSION......Page 760 Glossary......Page 761 References......Page 763 Clustered Regularly Interspaced Short Palindromic Repeats......Page 768 Knockouts via Double-Strand Breaks......Page 769 Nickases......Page 770 Homology-Directed Repair......Page 771 SpCas 9 Variants and Orthologues......Page 772 Transcription Activator-like Effector Nucleases......Page 773 Recombinase......Page 774 Proteins......Page 775 DELIVERY METHODS......Page 776 Liver......Page 777 Muscle: Muscular Dystrophy......Page 778 Duchenne Muscular Dystrophy......Page 779 Blood......Page 780 Retina......Page 781 References......Page 782 BIOMINERALIZATION AND BONE REGENERATION......Page 788 Mesenchymal Stem Cells......Page 789 Biochemical Signaling: Growth Factors and Cell Signals......Page 790 In Vivo Preclinical Models......Page 791 Selection Considerations Based on Animal Species......Page 792 References......Page 793 INTRODUCTION......Page 796 ADVANCE OF IN VITRO ORGANOID DEVELOPMENT: PROGRESSION FROM TWO-DIMENSIONAL TO THREE-DIMENSIONAL MODELS......Page 797 Microengineering and Biofabrication......Page 799 Vessel-on-a-Chip......Page 800 Cancer-on-a-Chip......Page 801 BODY-ON-A-CHIP: MULTIORGAN SYSTEMS AND FUTURE APPLICATIONS......Page 802 Cancer......Page 803 Drug Testing and Toxicology......Page 804 Additional Disease Modeling......Page 805 The Ex Vivo Console of Human Organoids Platform......Page 806 Other Body-on-a-Chip Programs......Page 807 Organ-on-a-Chip Systems for Personalized Precision Medicine......Page 809 References......Page 810 DESIGN CONSIDERATIONS FOR CREATING BIOREACTORS......Page 814 Bioengineering Functional Lungs......Page 815 Bioreactors for Regeneration of Small Animal Lungs......Page 816 In Vivo Bioreactors for Lung Regeneration......Page 817 Bioreactors for Study of Lung Biology......Page 819 Evaluation of Bioengineered Lungs......Page 820 Perfusion Bioreactors for Bone Regeneration......Page 822 In Vivo Bone Bioreactors for Solving the Vascularization Problem......Page 824 Bioreactors for Studying Bone Development and Disease......Page 825 Monitoring the Environment and Tissue Development Within Bioreactors......Page 826 References......Page 828 FUNDAMENTALS OF THREE-DIMENSIONAL PRINTING......Page 832 Extrusion-Based Printing......Page 833 Inkjet Bioprinting......Page 834 BIOINKS......Page 835 Matrix or Matrix-Mimicking Bioinks......Page 837 Synthetic Materials......Page 838 Natural Materials......Page 840 Co-printing and Hybrid Bioinks......Page 843 Cell-Laden Bioinks......Page 846 Sacrificial Bioinks......Page 848 Supporting Bioinks and Supporting Baths......Page 850 In Vitro Applications......Page 852 CONCLUSION AND FUTURE DIRECTIONS......Page 853 References......Page 854 BIOPRINTING STRATEGY: FROM MEDICAL IMAGE TO PRINTED TISSUE......Page 858 Jetting-Based Printing......Page 859 Hybrid and Other Mechanisms......Page 861 Synthetic Hydrogels......Page 862 Naturally Derived Hydrogels......Page 863 Biodegradable Synthetic Polymers for Structural Integrity......Page 864 Three-Dimensional Bioprinted Vascular Structures......Page 865 Tumor Models......Page 866 Bone......Page 868 Cartilage......Page 869 Skeletal Muscle and Tendon......Page 872 Skin......Page 873 CONCLUSIONS AND FUTURE PERSPECTIVES......Page 874 Glossary......Page 875 References......Page 876 Fracture Healing......Page 880 Adipose-Derived Stem Cells......Page 881 Induced Pluripotent Stem Cells......Page 882 Porous and Highly Interconnected Scaffolds......Page 883 Nanofibrous Scaffolds for Bone Tissue Engineering......Page 884 Hydrogels......Page 885 Bone Morphogenetic Proteins......Page 886 Nucleotide Delivery and Gene Therapy......Page 887 IMMUNOMODULATION IN BONE REGENERATION......Page 888 T Cells......Page 889 References......Page 890 STRUCTURE OF THE INNER EAR......Page 894 HAIR CELL LOSS......Page 895 HISTORY OF HAIR CELL REGENERATION......Page 896 SPONTANEOUS HAIR CELL REGENERATION IN MAMMALIAN VESTIBULAR ORGANS......Page 897 INSIGHTS FROM DEVELOPMENTAL BIOLOGY......Page 898 INDUCTION OF HAIR CELL REGENERATION USING TRANSGENIC MICE......Page 902 STUDIES OF HAIR CELL REGENERATION USING THE LATERAL LINE......Page 903 FORMATION OF NEW NEUROMASTS FROM MULTIPOTENT PROGENITORS......Page 904 HAIR CELL REGENERATION IN THE LATERAL LINE......Page 905 PATHWAYS COORDINATING HAIR CELL REGENERATION IN THE LATERAL LINE......Page 906 OPEN QUESTIONS ABOUT LATERAL LINE REGENERATION......Page 907 References......Page 908 UNDERSTANDING THE CRANIOFACIAL REGENERATIVE ENVIRONMENT......Page 914 CURRENT METHODS OF MAXILLOFACIAL RECONSTRUCTION......Page 917 Ceramics......Page 918 Bioactive Molecules......Page 919 Platelet-Derived Growth Factor......Page 920 Bone Marrow Aspirate Concentrate Technique......Page 921 Bioreactors......Page 924 Antibiotics......Page 925 CONCLUSION......Page 926 List of Abbreviations......Page 928 References......Page 929 INTRODUCTION......Page 934 TOOTH DEVELOPMENT......Page 935 DENTAL STEM CELLS......Page 936 DENTAL TISSUE ENGINEERING......Page 937 Whole Tooth Engineering......Page 939 Dental Pulp and Dentin Regeneration......Page 940 Periodontal Regeneration......Page 941 Alveolar Bone Regeneration......Page 943 List of Abbreviations......Page 944 References......Page 945 INTRODUCTION......Page 950 Red Blood Cells Generated From Adult Stem Cells In Vitro......Page 951 Red Blood Cells Generated From Human Embryonic Stem Cells......Page 952 Red Blood Cells Generated From Human Induced Pluripotent Stem Cells......Page 954 Where Do We Go From Here?......Page 955 Generation of Megakaryocytes and Platelets From Adult Stem Cells and Somatic Cells......Page 956 Improving the Efficiency for In Vitro Platelet Production......Page 957 HEMATOPOIETIC STEM CELLS......Page 958 References......Page 960 Further Reading......Page 963 CARTILAGE AND CARTILAGE REPAIR......Page 964 Cartilage Surface Modification......Page 965 Bioscaffolds in Cartilage Repair......Page 966 Chitosan......Page 967 Synthetic Scaffolds......Page 968 Biological Factors......Page 969 Bioreactors......Page 970 Clinical Translation......Page 972 CURRENT AND FUTURE TRENDS IN CARTILAGE ENGINEERING......Page 973 References......Page 974 Regulatory and Financial Challenges to Stem Cell Therapies......Page 980 STEM CELL THERAPIES FOR MUSCULOSKELETAL DISEASES......Page 981 Bone......Page 982 Articular Cartilage......Page 983 Osteochondral Tissue......Page 985 Tendon and Ligament......Page 986 Tendon–Bone Interface: Enthesis......Page 987 Meniscus......Page 988 Intervertebral Disc......Page 989 Skeletal Muscle......Page 990 CHALLENGES AND PROSPECTS......Page 991 References......Page 993 SATELLITE CELL–DERIVED MYOBLASTS MEET THE PROPERTIES NEEDED FOR TRANSPLANTATION IN SKELETAL MUSCLES......Page 998 Gene Complementation......Page 999 Formation of New Myofibers......Page 1000 Formation of Graft-Derived Satellite Cells......Page 1002 Technical Approaches for Intramuscular Transplantation......Page 1003 Potential Risks of the Cell Injection Procedure......Page 1004 Improving the Efficiency of Cell Injections......Page 1006 Initial Survival......Page 1007 Long-term Survival......Page 1008 CONCLUSIONS......Page 1009 References......Page 1010 Background......Page 1014 History of Islet Transplantation......Page 1015 The Edmonton Protocol......Page 1016 Patient Assessment and Selection......Page 1017 Islet Transplantation Procedure......Page 1018 Immunosuppressive Therapy and Complications......Page 1019 Living Donor Islet Transplantation......Page 1020 Stem Cell Transplantation......Page 1022 Optimal Transplantation Site......Page 1024 Improving Engraftment Posttransplant......Page 1025 Improved Immunomodulation: Toward Donor-Specific Tolerance......Page 1026 References......Page 1028 FETAL DEVELOPMENT AND REGENERATIVE MEDICINE......Page 1036 PRECLINICAL ANIMAL STUDIES OF IN UTERO STEM CELL TRANSPLANTATION......Page 1038 Barriers to In Utero Stem Cell Transplantation Success......Page 1040 The Need for Better Hemophilia A Treatments......Page 1042 Feasibility and Justification for Treating Hemophilia A Before Birth......Page 1043 Genomic Integration-Associated Insertional Mutagenesis......Page 1045 Genome Editing......Page 1046 CLINICAL EXPERIENCE WITH IN UTERO STEM CELL TRANSPLANTATION......Page 1047 References......Page 1048 INTRODUCTION......Page 1056 Xenogenic Matrices......Page 1057 Tissue Engineering by Self-assembly......Page 1059 Extracell