Stem Cells in the Respiratory System (eBook)

Preface 5
Contents 7
Contributors 8
1 Stem and Progenitor Cells of the Airway Epithelium 10
1 Introduction 10
1.1 Tissue-Specific Stem Cells 10
1.2 Lung-Epithelial-Tissue-Specific Stem Cells 10
1.3 Facultative Progenitor Cell 11
1.4 Lung Facultative Progenitor Cells 11
1.5 Questions Relevant to Lung Stem Cells 11
2 Conducting Airway Structure and Function 12
2.1 Functional Domains 12
2.2 Tracheobronchial Domain 12
2.3 Bronchiolar and Terminal Bronchiolar Domain 12
2.4 Origin of Airway Domains 13
2.5 Birth Date of Airway Epithelial Cells 13
3 Conducting Airway Progenitor Cell Types 14
3.1 Tracheobronchial Epithelium 14
3.2 Basal Cells 14
3.2.1 Basal Cells -- Surface Epithelium 14
3.2.2 Basal Cells -- Submucosal Glands 14
3.2.3 Basal Cells -- Plural Membrane 15
3.3 Secretory Cells 15
3.3.1 Clara-Like and Clara Cells 15
3.3.2 Secretory Cell Molecular Markers 16
3.3.3 Secretory Cells -- Cellular Specialization 16
3.3.4 Secretory Cells -- Submucosal Gland 16
3.4 Bronchiolar Epithelium 17
3.4.1 Clara Cells 17
3.4.2 Pulmonary Neuroendocrine Cells 17
4 Facultative Progenitor Cell Pools 18
4.1 Basal Cells 18
4.1.1 Steady-State and Reparative Basal Cells 18
4.2 Clara-Like and Clara Cells 18
4.2.1 Phenotypic Plasticity Is a Hallmark of Clara-Like and Clara Cells 19
5 Evidence in Support of Lung Stem Cells 19
5.1 Classic Stem Cell Methods 19
5.2 Injury and Lung Stem Cell Analysis 20
5.3 Injury as a Confounding Variable 21
5.4 Tracheobronchial Stem Cells 21
5.4.1 Evidence in Favor of a Tracheobronchial Stem Cell 21
5.4.2 Distinctions Between the Human and Mouse Data Sets 21
5.4.3 Predictions of the Classic Stem Cell Model 23
5.4.4 Revision of the Classic Hierarchical Organization 23
5.4.5 A Temporally Regulated Tissue-Specific Stem Cell Hierarchy 24
5.5 Bronchiolar Stem Cells 26
5.5.1 Evidence in Favor of a Bronchiolar Stem Cell 26
5.5.2 Caveats to the ''Stemness'' Claim 26
5.5.3 Compartmental Boundaries 26
5.5.4 Phenotypic Plasticity 26
5.5.5 Fulfilling Koch's Postulates 27
6 Summary 27
7 Future Directions 28
References 28
2 Mesenchymal Stem Cells for Lung Repair and Regeneration 34
1 Introduction 34
2 Identification, Characterization, and Culture of MSCs 35
3 MSCs of Different Tissue Origins: Similarities and Differences 36
4 Acquisition of an Airway or Alveolar Epithelial Phenotype by MSCs 37
5 Immunomodulation of Lung Injuries by MSCs 38
6 Clinical Use of MSCs in Lung Disease 41
7 MSCs and Malignancies: Pros and Cons and Other Cautions for Use 41
8 Summary 42
References 43
3 The Role of Progenitor Cells in Lung Disease Prognosis 52
1 Introduction and Background 52
2 Asthma 55
3 Pulmonary Arterial Hypertension 57
4 Pulmonary Fibrosis 59
5 Chronic Obstructive Pulmonary Disease and Emphysema 60
6 Acute Lung Injury/Acute Respiratory Distress Syndrome 61
6.1 Sepsis 64
7 Lung Cancer 65
8 Additional Considerations 66
Acknowledgments 67
References 67
4 The Role of Fibrocytes in Lung Repair and Fibrosis 72
1 Introduction 72
2 The Fibrocyte 73
2.1 Characteristics Suggesting a Bone Marrow Origin 73
2.2 Diverse Functions That Promote Tissue Repair and Fibrosis 75
2.3 Homing of Fibrocytes and the CXCR4--CXCL12 Axis 76
2.4 Role of Fibrocytes in Human Idiopathic Pulmonary Fibrosis 79
2.5 Effect of Hypoxia on the Circulating Fibrocyte 80
2.6 Role of Fibrocytes in Human Asthma 81
3 Conclusion 82
References 82
5 Stem Cells and CellMatrix Interactions in Lung 86
1 Introduction 86
2 Extracellular Matrix in Lung 87
2.1 Lung Extracellular Matrix in Health and Disease 87
2.1.1 Collagens 88
2.1.2 Elastin 88
2.1.3 Proteoglycans 88
2.1.4 Laminins 89
2.1.5 Fibronectins 89
2.2 Extracellular Matrix Recognition Through Integrins 90
3 Stem CellExtracellular Matrix Interactions 92
3.1 Stem Cells Recognize and Influence the Extracellular Matrix 94
3.2 Extracellular Matrix and Stem Cells in Lung Development 95
3.3 Extracellular Matrix and Lung Tissue Bioengineering 96
3.4 Extracellular Matrix in Cancer Stem Cells 98
3.5 Extracellular Matrix and Stem Cells in Lung Injury 98
4 Research Needs 99
5 Conclusion 100
References 100
6 Mobilization of Stem Cells/Progenitor Cells by Physical Activity 106
1 Introduction 106
2 Characterization of Stem and Progenitor Cells 107
3 Stem Cell Sources 108
4 Principal Mechanism of Stem and Progenitor Cell Activation/Mobilization 111
5 Activation of Stem and Progenitor Cells by Physical Activity 111
5.1 Satellite Cells/Myogenic Stem Cells 112
5.2 Bone-Marrow-Derived Stem and Progenitor Cells (Mesenchymal) 114
5.3 Hematopoietic Stem/Progenitor Cells 116
5.4 Endothelial Progenitor Cells 117
5.5 Neuronal Stem Cells 118
5.6 Stem Cells from Other Sources 120
6 Future Perspectives 121
References 122
7 Mesenchymal Stem Cells for Acute Lung Injury 130
1 Introduction 130
2 Background 131
3 MSCs in Animal and Human ALI Models 132
4 Mechanism (Engraftment) 134
5 Mechanism (Immunomodulation) 136
6 Mechanism (Alveolar Fluid Clearance) 139
7 Mechanism (Lung Endothelial Permeability) 140
8 Challenges 141
9 Conclusions 142
References 142
8 Animal Models of Lung Injury: Role for Mesenchymal Stem Cells 150
1 Introduction 150
2 MSCs and Animal Models of ALI 150
3 MSCs and Cystic Fibrosis 153
4 MSCs and COPD 153
5 MSCs and Pulmonary Hypertension 154
6 MSCs and Asthma and Allergy 155
7 MSCs and Fibrotic Lung Disorders 156
8 MSCs and Lung Transplant 158
9 MSCs and Oxidative Stress 158
9.1 Oxidative Stress in ALI 158
9.2 Antioxidant Defense Systems in MSCs 159
9.3 MSCs and Thiol/Disulfide Redox State 161
10 MSCs and the Alcoholic Lung 162
10.1 Alcohol Abuse and the Lung 162
10.2 MSCs and the Alcoholic Lung 162
11 Conclusions 163
References 163
Index 168