Regenerative Biology and Medicine

Chapter 1: An Overview of Regenerative Biology and Medicine

Introduction

A Brief History of Regenerative Biology and Medicine

The Biology of Regeneration


1. Regeneration Takes Place at all Levels of Biological Organization


2. Mechanisms of Regeneration at the Tissue Level


3. Epimorphosis and Morphallaxis


4. Evolutionary Significance of Regeneration and Fibrosis

Strategies of Regenerative Medicine


1. Cell Transplantation


2. Bioartificial Tissues


3. Induction of Regeneration In Situ

Summary

References

Chapter 2: Repair of Skin Wounds by Fibrosis

Introduction

Structure of Adult Mammalian Skin

The Effect of Wound Type and Extent on Dermal Repair

Phases of Repair in Excisional Wounds


1. Hemostasis and Clot Formation


2. Inflammation


3. Structural Repair


4. The Role of Wound Contraction in Dermal Repair

Molecular Comparison of Wounded vs. Unwounded Skin

Fetal Skin Heals Without Scarring


1. Cellular and ECM Differences Between Fetal and Adult Wound Healing


2. Fetal Wounds have a Minimal Inflammatory Response

Summary

References


Chapter 3: Regeneration of Epidermal Tissues

Introduction

Regeneration of Epidermis and Hair


1. Maintenance Regeneration


2. Injury-Induced Regeneration of the IFE

Regeneration of Nails

Regeneration of Dental Tissues

Regeneration of the Lens


1. Structure of the Eye and Lens


2. Cellular Events of Lens Regeneration in the Newt Eye


3. Transcription Factors Regulating Lens Regeneration


4. Signals Invlved in Lens Regeneration


5. Mammals Have Some Capacity for Lens Regeneration

Regeneration of the Cornea

Summary

References

Chapter 4: Regenerative Medicine of Skin, Hair and Dental Tissues

Introduction

Repair of Skin


1. Acceleration of Acute Wound Repair by Topically Applied Agents


2. Acceleration of Repair in Chronic Wounds by Topically Applied Agents


3. Keratinocyte Transplants


4. Bioartificial Skin Equivalents


5. Acellular Dermal Regeneration Templates

Use of Acellular Templates for Abdominal Wall Repair

Stimulation of Hair Regeneration

Repair of Teeth and Peridontium

Corneal Regeneration

Summary

References

Chapter 5: Regeneration of Neural Tissues

Introduction

Axon Regeneration


1. Axons of Mammalian Spinal (Peripheral) Nerves


2. Axons of Mammalian Spinal Cord


3, Axons of Amphibian Spinal Cord


4. Axons of Amphibian and Fish Optic Nerve

Maintenance Regeneration of Neurons in the Mammalian CNS


1. Discovery of Neural Stem Cells


2. Regeneration of Olfactory Nerve and Bulb Neurons


3. Regeneration of Hippocampal Neurons


4. Regeneration of Cortical Neurons


5. The CNS Neural Stem Cell Microniche

Injury-Induced CNS Regeneration


1. Avian and Mammalian Auditory Sensory Neurons


2. Regeneration of Neurons in the Mammalian Brain


3. Regeneration of the Retina


4. Regeneration of the Spinal Cord in Amputated Amphibian and Lizard Tails

Summary

References

Chapter 6: Regenerative Medicine of Neural Tissues

Introduction

Therapies for Injured Peripheral Nerve

Therapies for Injured Spinal Cord


1. Pharmaceutical Therapies


2. Regeneration Templates


3. Cell Transplant Therapies


4. Bioartificial Spinal Cord


5. Rehabilitation Programs and Synaptic Plasticity


6. Combinatorial Approaches May Bring Better Success

Therapies for Neurodegenerative Diseases


1. Demyelinating Disorders


2. Parkinson¡¦s Disease


3. Huntington¡¦s Disease


4. Alzheimer¡¦s Disease


5. Amyotrophic Lateral Sclerosis

Summary

References


Chapter 7: Regeneration of Digestive, Respiratory and Urogenital Tissues

Introduction

Intestinal Epithelium


1. Structure of the Intestinal Tract


2. Regeneration of the Villous Epithelium


3. Regeneration of Transected Intestine

Liver


1. Structure and Function of the Mammalian Liver


2. Regeneration by Compensatory Hyperplasia


3. Injury-Induced Regeneration via Stem Cells


4. Heterogeneity of Hepatocyte Size and Growth Potential

Pancreas


1. Structure and Function of the Pancreas


2. Regeneration of the Pancreas


3. Origin of Regenerated ƒÒ-Cells

Alveolar Epithelium of the Lung


1. Structure of the Respiratory System


2. Regeneration of Alveolar Epithelium

Kidney and Urinary System


1. Structure of the Kidney and Urinary System


2. Regeneration of Kidney Tubule Epithelium

Gonads

Prostate Tissue

Summary

References

Chapter 8: Regenerative Medicine of Digestive, Respiratory and Urinary Tissues

Introduction

Regenerative Therapies for the Liver


1. Hepatocyte Transplants


2. Extracorporeal Liver Assist Devices

Regenerative Therapies for the Pancreas


1. Cell Transplants


2. Suppression of Autoimmunity and Regeneration From Remaining ƒÒ-Cells


3. Bioartificial Pancreas


4. Gene Therapy to Induce Islet Neogenesis


Regenerative Therapies for the Esophagus and Intestine


1. Esophagus


2. Intestine


Regenerative Therapies for the Respiratory System


1. Trachea


2. Lung


Regenerative Therapies for the Urinary System


1. Nephrons


2. Urinary Conduit Tissue

Summary

References


Chapter 9: Regeneration of Musculoskeletal Tissues

Introduction

Regeneration of Skeletal Muscle


1. Structure of Skeletal Muscle


2. Satellite Cells are the Source of Regenerated Muscle


3. Cellular and Molecular Events of Skeletal Muscle Regeneration


4. The Activation and Proliferation of SCs is Regulated by a Variety of Signaling Molecules


5. Tension and Innervation are Required for Normal Muscle Regeneration

Regeneration of Bone


1. Structure of Bone


2. Maintenance Regeneration of Bone


3. Injury-Induced Regeneration of Bone

Repair of Articular Cartilage

Repair of Tendon and Ligament


1. Structure of Tendons and Ligaments


2. Repair of Tendons and Ligaments

Summary

References

Chapter 10: Regenerative Medicine of Musculoskeletal Tissues

Introduction

Regenerative Therapies for Muscle


1. Muscular Dystrophy


2. Bioartificial Muscle

Regenerative Therapies for Meniscus and Articular Cartilage


1. Meniscus


2. Articular Cartilage

Regenerative Therapies for Bone

1. Electromagnetic Field Stimulation


2. Ilizarov Distraction Technique for Lengthening Bones


3. Induction of Bone Regeneration by Osteogenic Factors and Acellular Templates


4. Cell Transplants and Bioartificial Bone


5. The Long Bones of Salamanders Can Regenerate When Removed

Regenerative Therapies for Tendon and Ligament


1. Tendon


2. Ligament

Summary

References

Chapter 11: Regeneration of Hematopoietic and Cardiovascular Tissues

Introduction

Regeneration of Hematopoietic Cells


1. Composition of Adult Blood


2. Hematopoietic Stem Cells of the Bone Marrow


3. Regulation of LT-HSC Activation and Proliferation

Regeneration of Blood Vessels


1. Development and Structure of the Vascular System


2. Blood Vessel Regeneration in Wounded Tissue

Regeneration of Cardiac Muscle


1. Structure of Cardiac Muscle


2. Mammalian Cardiac Muscle Does Not Regenerate, but Harbors Adult Stem Cells


3. Amphibian and Zebrafish Cardiac Muscle Regenerates When Injured

Summary

References

Chapter 12: Regenerative Medicine of Hematopoietic and Cardiovascular Tissues

Introduction

Therapies for Hematopoietic Disorders


1. Myeloablative Therapy


2. Non-Myeloablative Therapy


3. The Future of Hematopoietic Transplants


4. Gene Therapy for Genetic Hematopoietic Diseases

Therapies for Blood Vessel Regeneration


1. Stem Cell Transplants


2. Acellular Regeneration Templates


3. Bioartificial Blood Vessels

Therapies for Protection and Regeneration of the Infarcted Myocardium


1. Transplants of Bone Marrow Cells


2. Satellite Cell Transplants


3. Cardiomyocyte Transplants


4. Soluble Factors and Myocardial Regeneration


5. Bioartificial Cardiac Muscle

Summary
References


Chapter 13: Regenerative Medicine: Developmental Plasticity of Adult Stem Cells

Introduction

Assays to Test Developmental Plasticity
Experimental Results


1. Neural Stem Cells


2. Satellite Cells


3. Liver Oval Cells


4. Dental Pulp Cells


5. Unfractionated Bone Marrow and HSCs


6. MSCs of the Bone Marrow and Related MSCs

Many Reports of Lineage Conversion are Due to Fusion With Host Cells

Adult Stem Cell Pluripotency: Fact or Fiction?

Might Organisms Contain ESC-Like Stem Cells in Their Tissues?

Effects of Aging on Number and Developmental Status of Regeneration-Competent Cells

Summary

References


Chapter 14: Regeneration of Appendages

Introduction

Amphibian Limb Regeneration


1. Events of Limb Regeneration


2. Origin of the Blastema


3. Mechanism of Blastema Formation


4. Epidermal and Neural Requirements for Survival and Proliferation of Blastema Cells


5. Developmental Plasticity of Blastema Cells in Regenerating Amphibian Limbs


6. Spatial Organization of Tissue Patterns in the Regenerating Limb


7. Stimulation of Frog Limb Regeneration


8. Comparative Analysis of Gene Activity in Regeneration-Competent vs. Regeneration-Deficient Limbs

Regeneration of Amphibian Jaws

Appendage Regeneration in Mammals


1. Regeneration of Ear Tissue


2. Regeneration of Deer Antlers


3. Regeneration of Mouse and Human Digit Tips


4. Stimulation of Digit and Limb Regeneration in Mice and Rats

Summary

References


Chapter 15: Research Issues in Regenerative Medicine

Introduction

Biological Issues and Challenges.


1. Cell Sources for Transplantation and Bioartificial Tissue Construction


2. Expansion and Directed Differentiation of Regeneration-Competent Cells xiii


3. Challenges for Bioartificial Tissue Construction


4. The Challenge of Immunorejection


5. Challenges for the Chemical Induction of Regeneration


6. The Challenge of Curing Disease

Bioethical Issues and Challenges


1. The Derivation of Designer Human ESCs by SCNT


2. The Controversy Over Human ESC Research

3. Resolving an Unresolvable Dilemma


4. The Specter of Interspecies Grafting

Concluding Remarks

Summary

References