Regenerative Nephrology (eBook)

Front Cover 1
Regenerative Nephrology 4
Copyright 5
Dedication 6
Contents 8
Contributors 12
Introduction 14
Part I -Phylogeny and Ontogeny of Tissue Regeneration 18
Chapter 1 Glomerulogenesis and De Novo Nephrogenesis in Medaka Fish: An Evolutionary Approach 20
Introduction 20
Medaka as a Model Animal for Kidney Research 21
Kidney Development in Medaka 22
Kidney Regeneration in Medaka 28
Perspectives 32
Conclusion 33
References 33
Chapter 2 Renal Organogenesis: Growing a Replacement Kidney In Situ from Transplanted Renal Primordia 36
Introduction 36
Methodology for Organogenesis 37
Renal Organogenesis 40
Alternatives to the Use of Embryonic Kidney Primordianbspto AchievenbspOrganogenesis 46
Current Challenges in the Application of Renal Organogenesis Technology 48
Conclusion 50
References 50
Chapter 3 Use of Genetic Mouse Models to Study Kidney Regeneration 54
Introduction 55
Genetic Modification In Vivo 55
Development of the Nephron: How Genetic Tools have Enabled Understanding of Nephron Formation 62
Adult Kidney Regeneration: How Genetic Tools have Enabled Understanding of Nephron Regeneration 64
Lessons from Generation of the Kidney: Can We Use Recent Insights and Developmental Tools to Regenerate the Kidney? 79
References 79
Part II -Mediators of Regeneration 84
Chapter 4 Endogenous Anti-inflammatory and Proresolving Lipid Mediators in Renal Disease 86
Introduction 86
Lipid Mediators: Chemical Autacoids in Inflammation and Resolution 89
Lipoxins 89
Proresolving Pathways, Essential Fatty Acids and Resolution Indices 91
Aspirin is Resolution Friendly 91
Statins and Anti-inflammatory Lipid Mediators 94
Lipoxins and Heme Oxygenase-1 System 95
Resolvins are Novel Endogenous Mediators: 18R E-Series and 17R D-Series Resolvins 95
Resolvin and Protectin Biosynthesis 97
Resolvins and Protectins in Disease Models 98
Corneal Damage: Epithelial Wound Healing 100
Renal Inflammation, Resolution and Fibrosis 101
Proresolving Therapeutics: Agonists of Resolution? 103
Conclusion 104
References 104
Chapter 5 Tissue Protection and Regeneration Aided by Erythropoietin and Erythropoietin-derived Peptides 110
Introduction 110
Tissue Expression of Erythropoietin and the Erythropoietin Receptor 110
Erythropoietin in the Vascular System 111
Erythropoietin and the Kidney 112
Conclusion 115
References 115
Chapter 6 Mast Cells in Kidney Regeneration 120
Introduction 120
Basic Biology of Mast Cells 121
Model Systems to Study Mast Cell Functions 125
Beneficial Role of Mast Cells in Inflammation 126
Mast Cells as Regulators of Immune and Inflammatory Reactions 127
Inflammation and Kidney Diseases: A Regenerative Perspective 128
Mast Cells in Kidney Disease 129
Positive Actions of Mast Cell Mediators in Kidney Disease 133
Conclusion 137
References 137
Chapter 7 Role of Macrophages in Renal Injury, Repair and Regeneration 142
Introduction 142
Injury, Repair and Regeneration of the Kidney 143
Macrophage Phenotype 144
Macrophages in Different Disease Models 145
Alternative Methods for Stimulating Macrophages 152
Alternative Sources of Macrophages 152
Regenerative Potential of Macrophages in Kidney Disease 153
Current Limitations in the Use of Macrophages as Cellular Therapy in Kidney Disease 153
Conclusion 154
References 154
Chapter 8 T-cell Contribution to Injury and Regenerative Processes in Kidney Diseases: Focus on Regulatory T Cells 158
Overview of T Cells in Kidney Diseases 158
Glomerulonephritis 160
Acute Kidney Injury 161
Kidney Transplantation 164
Conclusion 164
References 164
Part III -Stem Cells in Regenerative Processes 168
Chapter 9 Mesenchymal Stem Cells 170
Introduction 170
The Mesenchymal Stem Cell 171
Amniotic Fluid-derived Stem Cells 171
Bone Marrow Plasticity and Renal Repair 172
Mesenchymal Stem Cells Ameliorate Renal Injury and Accelerate Repair 173
Efficacy of Mesenchymal Stem Cell Therapy in Chronic Kidney Diseases 173
Do Exogenous Mesenchymal Stem Cells Directly Engraft into Injured Tubules? 173
Homing of Exogenous Mesenchymal Stem Cells 175
Evidence that Mesenchymal Stem Cells Repair Kidney by Paracrine and Endocrine Mechanisms 176
Paracrine Effects of Mesenchymal Stem Cells in Other Organs 177
Mesenchymal Stem Cell-derived Microvesicles and Acute Kidney Injury 178
Recruitment of Endogenous Bone Marrow Mesenchymal Stem Cells 178
Kidney Mesenchymal Stem Cells 178
Clinical Trials for Mesenchymal Stem Cells in Acute Kidney Injury, Graft Tolerance and Lupus Nephritis 179
Conclusion 180
References 180
Chapter 10 Endothelial Progenitor Cells and the Kidney 184
Introduction 184
The Concept of Endothelial Progenitor Cells 185
Endothelial Progenitor Cells as an Indicator of Cardiovascular Disease 185
Microvascular Remodeling by Circulating Cells 187
References 188
Chapter 11 Potential of the Side Population in Regenerative Nephrology 190
What is the Side Population? 190
Role of ABC Transporters: Markers or Mediators of Stem Cells 191
Existence of Side Population from Other Organs and their Association with Organ Regeneration 191
Does Dye Efflux Equal Stem Cell? 193
Fusion Versus Transdifferentiation: Does it Matter? 193
Origin of Non-Bone Marrow Side Population Cells 194
Heterogeneity Within Distinct Side Population Fractions 194
Identification of Side Population Cells Within the Embryonic and Adult Kidney 195
Gene Expression Profile and Immunophenotype of Kidney Side Population 195
Origin of and Cellular Heterogeneity Within the Kidney Side Population 196
Renal Side Population Multipotentiality and Renal Regenerative Potential 198
Potential Mechanism of Humoral Activity 199
Functional and Phenotypic Overlap between Kidney Side Population and Other Putative Endogenous Renal Stem Cells 200
Potential Regenerative Applications of Kidney Side Population 201
Conclusion 202
References 203
Chapter 12 Very Small Embryonic-like Stem Cells and Their Potential Relevance for Kidney Homeostasis 206
Introduction 206
Developmental Overview on Stem Cell Compartment 208
Deposition of Developmentally Early Stem Cells in Adult Tissues 208
Isolation of Very Small Embryonic-like Stem Cells 209
Regeneration Potential of Very Small Embryonic-like Stem Cells 211
Developmental Origin of Very Small Embryonic-like Stem Cells 212
Germ Line as Origin and Scaffold System for Tissue-committed Stem Cells in the Adult Body 212
Molecular Mechanisms Governing Quiescence of Very Small Embryonic-like Stem Cells: Involvement of Imprinted Genes 214
Molecular Signature Of Mrna From Adult Bone Marrow- Rived Very Small Embryonic-Like Stem Cells Supports Their Developmental Epiblast/Germ-Line Origin 215
Potential Role of very Small Embryonic-like Stem Cells in Pathology: Potential Cancer Stem Cells? 215
Applications to Other Areas of Health and Disease 216
References 217
Chapter 13 Induced Pluripotent Stem Cells 220
Introduction 220
Mechanisms of Kidney Development 221
Animal Cap in Fertilized Eggs of Amphibians 222
Embryonic Stem Cells 223
Creation of Induced Pluripotent Stem Cells 223
Cells and Animals to Use for the Generation of Induced Pluripotent Stem Cells 224
Mechanistic Understanding of Reprogramming Processes 224
Improving Methods for Induced Pluripotent Stem Cell Induction 225
Increasing Efficiency of Induced Pluripotent Stem Cell Induction 226
Complete Pluripotency 227
Disease Modeling with Patient-derived Induced Pluripotent Stem Cells 227
Toxicology Screening Using Induced Pluripotent Stem Cells and Embryonic Stem Cells 227
Future Directions in Induced Pluripotent Stem Cell Research and Technology 228
Cues to Regenerate Kidney Lineage Cells from Induced Pluripotent Stem Cells and Embryonic Stem Cells 228
Conclusion 229
References 230
Chapter 14 Methods of Isolation and Culture of Adult Stem Cells 234
Introduction 234
Methods for the Isolation and Culture of Bone Marrow Stem Cells 237
Isolation and Culture of Renal Progenitor Cells 240
Methods for the Isolation and Culture of Mesenchymal Stem Cells 240
Isolation and Culture of Human Adipose Tissue-derived Pericytes 243
References 244
Part IV -Stem Cells – from the Niche to Repair 248
Chapter 15 Stem Cell Niche in the Kidney 250
Introduction 250
Stem Cells in the Adult Kidney 250
Ontogenesis of the Renal Stem Cell Niche 252
The Adult Renal Stem Cell Niche 253
The Renal Niche in Aging 255
The Renal Niche in Glomerular Disorders 256
Conclusion 258
References 258
Chapter 16 Bioartificial Stem Cell Niches: Engineering a Regenerative Microenvironment 262
Introduction 262
Design Criteria for Creating a Bioartificial Niche 263
Chemistry of Bioartificial Niches 263
Fabrication Techniques 265
Common Hydrogel Materials 267
Examples of Hydrogel Applications 268
Recruitment and Delivery of Stem and Progenitor Cells to and from Artificial Niches 269
Extracellular Scaffold as a Mold for Kidney Regeneration 270
Hydrogel Encapsulation of Endothelial Progenitor Cells Protects Cells from Cytotoxins and Improves Their Viability 270
References 270
Chapter 17 Imaging of Transplanted and Native Stem Cells 274
Introduction 274
Methodologies for Labeling Stem Cells 275
Imaging Modalities 275
Conclusion 285
References 286
Part V -Causes of Regenerative Failure 290
Chapter 18 Stem Cell Injury and Premature Senescence 292
Introduction 292
Molecular Mechanisms of Stem Cell Exhaustion 294
Impairment of Stem Cell Function 296
In Vivo and Ex Vivo Therapy of Stem and Endothelial Progenitor Cells 300
Potential Mechanisms of Stem Cell-induced Organ Repair 300
Use of Artificial Niches to Store and Deliver Endothelial Progenitor Cells 301
References 301
Chapter 19 Regeneration and Aging: Regulation by Sirtuins and the NAD+ Salvage Pathway 306
Introduction 306
Aging of the Kidney 307
Cellular Basis of Tissue Aging 308
Molecular Mechanisms Underlying Cellular Aging 309
NAD+ Biosynthesis and Cell Health 312
Conclusion 313
References 313
Chapter 20 Bone Marrow Mesenchymal Stem Cells in Organ Repair and Strategies to Optimize their Efficacy 316
Introduction 316
Do Adult Bone Marrow-derived Stem Cells Participate in Kidney Repair? 317
Bone Marrow Mesenchymal Stem Cell Therapy Contributes to Renal Repair 317
Strategies to Enhance Stem Cell Effects 321
Conclusion 326
References 326
Part VI -Emerging Clinical Aspects of Stem Cell Therapy 330
Chapter 21 Treatment of Acute Kidney Injury with Allogeneic Mesenchymal Stem Cells: Preclinical and Initial Clinical Data 332
Acute Kidney Injury: Clinical and Experimental Issues 333
Treatment of Acute Kidney Injury with Stem Cells: Preclinical Studies 336
Phase I Clinical Trial 349
Prevention And Treatment Of Postoperative Acute Kidney Injury With Allogeneic Mesenchymal Stem Cells In Patients Who Require On-Pump Cardiac Surgery 349
References 354
Chapter 22 Clinical Trials in Renal Regenerative Medicine 358
Introduction 358
Clinical Trials of Regenerative Medicine in Other Disciplines 359
Clinical Trials on Renal Regeneration 363
Future Perspectives in Clinical Regenerative Nephrology 364
References 370
Chapter 23 Potential Risks of Stem Cell Therapies 378
Introduction 378
Technical Caveats in Stem Cell Preparation and Administration 381
Potential Clinical Problems of Stem Cell Therapies: Tumor Formation, Ectopic Tissue and Other Unwanted Effects 388
A Different Concept: Stimulation of Intrarenal Resident Stem Cell Populations 396
The Human Risk Factor: Stem Cell Cures 396
Conclusion 396
References 397
Chapter 24 Tissue Engineering in Urology 406
Introduction 406
Basic Components of Tissue Engineering 407
Tissue Engineering of Specific Genitourinary Organs 411
Conclusion 415
References 415
Chapter 25 Ethics in Regenerative Medicine 418
Introduction 418
Alternative Methods 420
References 423
Chapter 26 Stem Cell Banking 426
Introduction 426
Basic Principles of Cell Banking 427
Donation 427
Collection 428
Processing 428
Storage 434
References 436
Index 438
Color Plates 444