Foundations of Regenerative Medicine - Clinical and Therapeutic Applications

Front Cover

Foundations of Regenerative Medicine

Copyright Page

Contents

Preface

List of Contributors

Part I: Introduction to Regenerative Medicine

Chapter 1. Current and Future Perspectives of Regenerative Medicine

REGENERATIVE MEDICINE: CURRENT AND FUTURE PERSPECTIVES

CONCLUSIONS

REFERENCES

Chapter 2. Fundamentals of Cell-Based Therapies

INTRODUCTION

RATIONALE FOR CELL-BASED THERAPIES

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

Chapter 3. Stem Cell Research

INTRODUCTION

STEM CELLS

STEM CELL MODULATION IN VITRO

REGENERATIVE MEDICINE

CONCLUSION

ACKNOWLEDGMENTS

INTERNET RESOURCES

REFERENCES

Part II: Biologic and Molecular Basis for Regenerative Medicine

Chapter 4. Molecular Organization of Cells

INTRODUCTION

CELLULAR MECHANISMS OF THE EMT

MOLECULAR CONTROL OF THE EMT

CONCLUSION

REFERENCES

Chapter 5. Cell–ECM Interactions in Repair and Regeneration

INTRODUCTION

COMPOSITION AND DIVERSITY OF THE ECM

RECEPTORS FOR ECM MOLECULES

SIGNAL TRANSDUCTION EVENTS DURING CELL–ECM INTERACTIONS

CELL–ECM INTERACTIONS DURING HEALING OF SKIN WOUNDS

CELL–ECM INTERACTIONS DURING REGENERATION

IMPLICATIONS FOR REGENERATIVE MEDICINE

REFERENCES

Chapter 6. Developmental Mechanisms of Regeneration

INTRODUCTION

MECHANISMS OF REGENERATION

STRATEGIES OF REGENERATIVE MEDICINE

CONCLUSION

ACKNOWLEDGMENT

REFERENCES

Chapter 7. The Molecular Basis of Pluripotency in Principles of Regenerative Medicine

INTRODUCTION TO PLURIPOTENCY

EXTRACELLULAR SIGNALING FACTORS AND SIGNAL TRANSDUCTION

TRANSCRIPTIONAL NETWORKS

EPIGENETIC AND ENVIRONMENTAL REGULATION

SUMMARY AND PERSPECTIVES

REFERENCES

Part III: Cells and Tissue Development

Chapter 8. Embryonic Stem Cells: Derivation and Properties

INTRODUCTION

DERIVATION OF ES CELLS

CULTURE OF ES CELLS

DEVELOPMENTAL POTENTIAL OF ES CELLS

CONCLUSION

ACKNOWLEDGMENT

REFERENCES

Chapter 9. Stem Cells Derived from Amniotic Fluid and Placenta

INTRODUCTION

CVS AND AMNIOCENTESIS

DIFFERENTIATED CELLS FROM AMNIOTIC FLUID AND PLACENTA

MESENCHYMAL CELL FROM PLACENTA AND AMNIOTIC FLUID

PLURIPOTENT STEM CELLS FROM PLACENTA AND AMNIOTIC FLUID

FUTURE DIRECTION

SUMMARY

REFERENCES

Chapter 10. Bone Marrow Stem Cells: Properties and Pluripotency

INTRODUCTION

BONE MARROW STEM CELLs

BMSCS AND TISSUE REGENERATION

IMPORTANT FACTORS REGULATING BMSC HOMING AND DIFFERENTIATION

CLINICAL APPLICATIONS OF BMSCS FOR CARDIAC REGENERATION

CONCLUSION

REFERENCES

Chapter 11. Mesenchymal Stem Cells

INTRODUCTION

THE DEFINITION OF MSCs

THE STEM CELL NATURE OF MSCs

SOURCE OF MSCs AND ISOLATION TECHNIQUES

WHICH TISSUES CONTAIN MSCs?

SKELETAL TISSUE REGENERATION BY MSCs

IMMUNOMODULATORY EFFECTS OF MSCs

NONSKELETAL TISSUE REGENERATION BY MSCs

CONCLUSIONS

REFERENCES

Chapter 12. Islet Cell Therapy and Pancreatic Stem Cells

INTRODUCTION

BENEFITS OF β-CELL REPLACEMENT THERAPY

CURRENT LIMITATIONS TO β-CELL REPLACEMENT THERAPY

ALTERNATIVE SOURCES OF INSULIN-PRODUCING CELLS: STEM CELLS AND β-CELL REGENERATION

PANCREATIC DEVELOPMENT

ISLET NEOGENESIS FROM ES CELLS

ISLET NEOGENESIS FROM ADULT STEM CELLS

TRANSDIFFERENTIATION

WHAT THE FUTURE MAY HOLD

ACKNOWLEDGMENTS

REFERENCES

Chapter 13. Mechanical Determinants of Tissue Development

INTRODUCTION

MECHANICAL FORCES EXPERIENCED BY TISSUES

THE CELL AS A SIGNAL RECEIVER AND PROCESSOR

OVERVIEW OF BIOREACTORS

PRACTICAL EXAMPLES OF MECHANICAL DETERMINANTS

CONCLUSION

REFERENCES

Chapter 14. Morphogenesis and Morphogenetic Proteins

INTRODUCTION

BMPs

STEM CELLS

SCAFFOLDS OF BIOMIMETIC BIOMATERIALS

CARTILAGE-DERIVED MORPHOGENETIC PROTEINS

REGENERATIVE MEDICINE AND SURGERY

ACKNOWLEDGMENTS

REFERENCES

Chapter 15. Physical Stress as a Factor in Tissue Growth and Remodeling

INTRODUCTION

STRUCTURAL HIERARCHY AND THE CONTINUUM CONCEPT

STRAIN AND STRESS DEFINITIONS

TISSUE GROWTH, REPAIR, AND REMODELING

MECHANOTRANSDUCTION MECHANISMS

IN VITRO MECHANICAL CONDITIONING

CONCLUSIONS

REFERENCES

Chapter 16. Engineering Cellular Microenvironments

INTRODUCTION

DEFINING THE CELLULAR MICROENVIRONMENT

DEFINING THE ORGANIZATION OF MULTICELLULAR CONSTRUCTS

DYNAMICALLY CHANGING THE MICROENVIRONMENT

CONCLUSIONS AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

REFERENCES

Chapter 17. Applications of Nanotechnology

INTRODUCTION

NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR CELL-BASED THERAPIES

NANOTECHNOLOGY AS A MULTI-FUNCTIONAL TOOL FOR BIOMATERIAL CONTROL

CONCLUSION

REFERENCES

Part IV: Biomaterials for Regenerative Medicine

Chapter 18. Design Principles in Biomaterials and Scaffolds

INTRODUCTION

SELECTION OF BIOMATERIALS

BIODEGRADABLE SYNTHETIC POLYMERS

DESIGN PRINCIPLES OF BIOLOGICAL SCAFFOLDS

SUMMARY AND CONCLUSION

REFERENCES

Chapter 19. Naturally Occurring Scaffold Materials

INTRODUCTION

COLLAGEN

CHITOSAN

INTACT EXTRACELLULAR MATRIX AS A SCAFFOLD MATERIAL

REFERENCES

Chapter 20. Synthetic Polymers

INTRODUCTION

NON-DEGRADABLE SYNTHETIC POLYMERS

BIODEGRADABLE SYNTHETIC POLYMERS FOR REGENERATIVE MEDICINE

APPLICATIONS OF SYNTHETIC POLYMERS

CONCLUSION/ SUMMARY

REFERENCES

Chapter 21. Surface Modification of Biomaterials

INTRODUCTION

PHYSICOCHEMICAL SURFACE MODIFICATIONS

OVERCOATING TECHNOLOGIES

BIOLOGICAL MODIFICATION OF SURFACES

SURFACE CHEMICAL PATTERNING

CONCLUSION AND FUTURE PROSPECTS

REFERENCES

Chapter 22. Biocompatibility and Bioresponse to Biomaterials

INTRODUCTION

INFLAMMATION (INNATE IMMUNITY) AND WOUND HEALING

FIBROSIS AND FIBROUS ENCAPSULATION

IMMUNOTOXICITY (ACQUIRED IMMUNITY)

SUMMARY

REFERENCES

Part V: Therapeutic Applications: Cell Therapy

Chapter 23. Islet Cell Transplantation

INTRODUCTION

CLINICAL ISLET TRANSPLANTATION

RISKS TO THE RECIPIENT

FUTURE CHALLENGES

SUMMARY AND CONCLUSIONS

REFERENCES

Chapter 24. Cell-Based Repair for Cardiovascular Regeneration and Neovascularization: What, Why, How, and Where Are We Going in the Next 5–10 Years?

INTRODUCTION

THE STATE OF CELL THERAPY

CELL-BASED REPAIR AS A MEANS OF REGENERATION IN CVD

VASCULAR INTEGRITY IS A BALANCING ACT IN WHICH INFLAMMATION IS KEY: INJURY VERSUS REPAIR

REPARATIVE POTENTIAL OF CELL THERAPY

CLINICAL STUDIES

WHAT IS REQUIRED FOR SUCCESSFUL REPAIR IN 2007 AND BEYOND?

SUMMARY

ACKNOWLEDGMENTS

REFERENCES

Chapter 25. Cell Therapies for Bone Regeneration

INTRODUCTION

CURRENT SOURCES OF OSTEOGENIC CELLS AND CELL ISOLATION TECHNIQUES

PRECLINICAL AND CLINICAL RESULTS

CONCLUSION: FUTURE DEVELOPMENTS AND CHALLENGES

REFERENCES

Chapter 26. Cell-Based Therapies for Musculoskeletal Repair

INTRODUCTION

BIOLOGY OF CELLS IN MUSCULOSKELETAL TISSUES

EMBRYONIC AND ADULT STEM CELLS

CELL-BASED THERAPIES AND TISSUE ENGINEERING

CONCLUSIONS AND PROSPECTS

ACKNOWLEDGMENTS

REFERENCES

Chapter 27. Hepatocyte Transplantation

INTRODUCTION

BACKGROUND STUDIES

CLINICAL HEPATOCYTE TRANSPLANTATION

HEPATOCYTE TRANSPLANTATION NOVEL USES, CHALLENGES, AND FUTURE DIRECTIONS

SUMMARY

REFERENCES

Chapter 28. Cell-Based Drug Delivery

INTRODUCTION

CELLS AND CELL PRODUCTS AS DRUG SOURCES

CELL ENCAPSULATION FOR THERAPEUTIC DELIVERY MACHINERY

CELL-BASED PROTEIN FACTORY

DRUG-LOADED TUMOR CELL SYSTEM

SUMMARY

REFERENCES

Part VI: Therapeutic Applications: Tissue Therapy

Chapter 29. Engineering of Large Diameter Vessels

INTRODUCTION

PREVALENCE AND IMPACT OF VASCULAR DISEASE

THE NEED FOR IMPROVED DIALYSIS VASCULAR ACCESS

VASCULAR PHYSIOLOGY RELEVANT TO TEBVs

TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE LITERATURE

TISSUE-ENGINEERED VASCULAR GRAFTS: A BRIEF REVIEW OF THE PROCESS

REFERENCES

Chapter 30. Cardiac Tissue

INTRODUCTION: FROM TISSUES TO ORGANS: KEY GOALS AND ISSUES

CELL AND GENE THERAPY

SCAFFOLD-BASED APPROACHES

TISSUE AND ORGAN FUNCTION

BIOREACTORS AND CONDITIONING

IMPLANTATION OF CARDIAC PATCHES

SUMMARY

REFERENCES

Chapter 31. Intracorporeal Kidney Support

INTRODUCTION

BASIC PRINCIPLES OF KIDNEY TISSUE REGENERATION

CREATION OF RENAL STRUCTURES IN VIVO

REGENERATION OF FUNCTIONAL RENAL TISSUE IN VIVO

SUMMARY

REFERENCES

Chapter 32. Genitourinary System

INTRODUCTION

RECONSTITUTION STRATEGIES

THE ROLE OF BIOMATERIALS

VASCULARIZATION

PROGRESS IN TISSUE ENGINEERING OF UROLOGIC STRUCTURES

ADDITIONAL APPLICATIONS

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

Chapter 33. Tissue Engineering of the Reproductive System

INTRODUCTION

MALE

FEMALE

REFERENCES

Chapter 34. Phalanges and Small Joints

INTRODUCTION

BASIC PRINCIPLES OF ENGINEERING PHALANGES AND SMALL JOINTS

CREATION OF COMPOSITE TISSUE STRUCTURES

SUMMARY AND FUTURE PERSPECTIVES IN CLINICAL TRANSLATION

REFERENCES

Chapter 35. Functional Tissue Engineering of Ligament and Tendon Injuries

INTRODUCTION

NORMAL LIGAMENTS AND TENDONS

HEALING OF LIGAMENTS AND TENDONS

MCL OF THE KNEE

APPLICATION OF FTE

SUMMARY AND FUTURE DIRECTIONS

ACKNOWLEDGMENT

REFERENCES

Chapter 36. Tissue Therapy: Implications of Regenerative Medicine for Skeletal Muscle

INTRODUCTION

THE NATURAL HEALING PROCESS OF SKELETAL MUSCLE

THE ROLE OF INFLAMMATION IN SKELETAL MUSCLE HEALING

PROMOTING REGENERATION AFTER SKELETAL MUSCLE INJURY

FIBROSIS PREVENTION: ANOTHER APPROACH TO IMPROVING SKELETAL MUSCLE HEALING

CONCLUSION

REFERENCES

Chapter 37. Peripheral Nerve Regeneration

INTRODUCTION

ISOTROPIC NERVE GRAFTS FOR REGENERATION

ANISOTROPIC NERVE GRAFTS

NATURAL NERVE GRAFTS

ANIMAL MODELS

SUMMARY

REFERENCES

Chapter 38. Innovative Regenerative Medicine Approaches to Skin Cell-Based Therapy for Patients with Burn Injuries

INTRODUCTION

CONVENTIONAL THERAPY AND CURRENT COMMERCIAL PRODUCTS

PROBLEMS IN THE FIELD

CELL APPLICATION INTO THE WOUND BY SPRAYING

PATIENT GROUPS AND SELECTION CRITERIA FOR CLINICAL STUDIES IN THE FIELD OF SKIN CELL-BASED THERAPY DEVELOPMENT IN BURN DISEASE PATIENTS

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…

SKIN PROGENITOR CELLS

REGULATORY ISSUES

DISCUSSION

ACKNOWLEDGMENT

REFERENCES

Part VII: Regulations and Ethics

Chapter 39. Ethical Considerations

ARGUMENTS THAT DO NOT WORK

ARGUMENTS THAT WORK

MORALITY AND THE SCOPE OF FUNDED RESEARCH

ETHICAL CONSTRAINTS

ACKNOWLEDGMENT

REFERENCES

Chapter 40. To Make is to Know: The Ethical Issues in Human Tissue Engineering

CASE STUDY

ARE THERE REASONS IN PRINCIPLE WHY PERFORMING THE BASIC RESEARCH SHOULD BE IMPERMISSIBLE?

DUTY AND HEALING: NATURAL MAKERS IN A BROKEN WORLD

TO MAKE IS TO KNOW: NOTES ON AN OLD PROBLEM ABOUT KNOWLEDGE

WHAT IS A THING: THE PERILS OF DECONSTRUCTION?

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?

WHAT PURPOSES, TECHNIQUES, OR APPLICATIONS WOULD BE PERMISSIBLE AND UNDER WHAT CIRCUMSTANCES?

WHAT PROCEDURES, STRUCTURES, INVOLVING WHAT POLICIES, SHOULD BE USED TO DECIDE ON APPROPRIATE TECHNIQUES AND USES?

CONCLUSION

Chapter 41. Overview of FDA Regulatory Process

INTRODUCTION AND CHAPTER OVERVIEW

BRIEF LEGISLATIVE HISTORY OF FDA

LAWS, REGULATIONS, AND GUIDANCE

FDA ORGANIZATION AND JURISDICTIONAL ISSUES

APPROVAL MECHANISMS AND CLINICAL STUDIES

MEETINGS WITH INDUSTRY, PROFESSIONAL GROUPS, AND SPONSORS

REGULATIONS AND GUIDANCE OF SPECIAL INTEREST FOR REGENERATIVE MEDICINE

ADVISORY COMMITTEE MEETINGS

FDA AND CRITICAL PATH SCIENCE

CONCLUSION

REFERENCES

Chapter 42. Current Issues in US Patent Law

WHAT ARE INTELLECTUAL PROPERTY RIGHTS?

WHY ARE INTELLECTUAL PROPERTY RIGHTS IMPORTANT?

HOW DO YOU VALUE INTELLECTUAL PROPERTY?

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