Biophysical Regulation of Vascular Differentiation and Assembly (eBook)

Biophysical Regulation of Vascular Differentiation and Assembly 3
Preface 5
Contents 7
Contributors 9
Chapter 1: The Emergence of Blood and Blood Vessels in the Embryo and Its Relevance to Postnatal Biology and Disease 15
1.1 Introduction 15
1.2 Concepts in Development of Blood and Blood Vessels 16
1.2.1 Embryonic Vasculogenesis 16
1.2.2 Embryonic Hematopoiesis 17
1.2.3 Historical Observations of the Lineage Relationship of Endothelium and Blood 18
1.3 Review of Hemogenic Endothelium Function During Embryogenesis 20
1.3.1 Yolk Sac 20
1.3.2 Aorto-Gonado-Mesonephros Region 20
1.3.3 Stem Cell Models of Vascular and Blood Cell Development 22
1.3.4 Phenotype and Origin of HSC in the Adult 23
1.3.5 Vascular Niche for Adult HSC 24
1.4 Future Directions 24
1.4.1 Potential Relationship of Hemogenic Endothelial Cells to Postnatal Vascular and Hematopoietic Progenitors? 24
1.4.2 Therapeutic Applications for Hemogenic Endothelium 25
1.4.3 Conclusions 27
References 27
Chapter 2: Molecular Control of Vascular Tube Morphogenesis and Stabilization: Regulation by Extracellular Matrix, Matrix Metalloproteinases, and EndothelialCell–Pericyte Interactions 31
2.1 Introduction 31
2.2 Concepts in Vascular Tube Morphogenesis in 3D Extracellular Matrices 32
2.2.1 Extracellular Matrix and Vascular Morphogenesis 32
2.2.2 Differential Effects of ECM Components on VascularTube Morphogenesis 33
2.3 Review of Work 34
2.3.1 Molecular Events Regulating Vascular Tube Morphogenesis and EC Sprouting in 3D Matrices 34
2.3.2 Functional Role of the Rho GTPases, Cdc42 and Rac1, and the Effectors, Pak2 and Pak4, in EC Tube Morphogenesis 36
2.3.3 Functional Role for PKCe and Src in EC Tube Morphogenesis and Subsequent Pak Activation Events 37
2.3.4 Cdc42 Coupling to Cell Polarity Pathways Controls EC Lumen and Tube Formation 38
2.3.5 Critical Functional Role for MT1-MMP in EC Lumen and Tube Formation in 3D Collagen Matrices 39
2.3.6 MT1-MMP-Dependent EC Lumen and Tube Formation Leads to the Formation of a Network of Physical Spaces Within the ECM Termed Vascular Guidance Tunnels 41
2.3.7 Cdc42 and MT1-MMP Are Functionally Interdependent Signaling Molecules, Which Are Components of an EC Lumen Signaling Complex That Controls EC Tubulogenesis in 3D Extracellular Matrices 42
2.3.8 Definition of an EC Lumen Signaling Complex That Controls Vascular Tube Morphogenesis 43
2.3.9 Critical Role for MMPs in the Molecular Control of Vascular Tube Regression Responses in 3D Collagen Matrices 45
2.3.10 Critical Functional Role for EC-Generated Vascular Guidance Tunnels During Blood Vessel Assembly in 3D Matrices 47
2.3.11 Pericyte Recruitment to Vascular Guidance Tunnels Induces Vascular Tube Stabilization 49
2.3.12 Molecular Mechanisms Underlying Why Pericytes Are Able to Stabilize EC-Lined Tube Networks 49
2.3.13 Pericyte Recruitment to EC-Lined Tubes StimulatesECM Remodeling Events and Vascular Basement Membrane Matrix Assembly 51
2.3.14 Critical Functional Role for Fibronectin Matrix Assembly During Vascular Development 53
2.3.15 Important Functional Role for Collagen Type IV in EC–Pericyte Tube Coassembly and Maturation Events 54
2.3.16 Pericyte TIMP-3 Contributes to Vascular Basement Membrane Matrix Assembly by Increasing Collagen Type IV Deposition or Stability 54
2.3.17 Specific Upregulation of EC and Pericyte Integrins Recognizing Basement Membrane Matrices During EC–Pericyte Tube Coassembly in 3D Collagen Matrices 55
2.4 Future Directions 56
References 57
Chapter 3: Scaffolding for Three-Dimensional Embryonic Vasculogenesis 62
3.1 Introduction 62
3.2 Developmental Cues for hESC Differentiation into Vascular Cells 63
3.3 EBs as a 3D Embryonic Vasculogenic Model 64
3.4 Scaffolds for Vascular Differentiation 66
3.4.1 General Considerations About Structure and Bioactivity of Scaffolds 68
3.4.2 Natural Scaffolds for Vascular Differentiation 70
3.4.3 Synthetic Scaffolds for Vascular Differentiation 73
3.5 Future Directions 74
References 76
Chapter 4: Intra- and Extracellular Microrheology of Endothelial Cells in a 3D Matrix 81
4.1 Introduction 81
4.2 Intracellular Microrheology of Cells Inside a 3D Matrix 82
4.2.1 Fundamentals of Particle-Tracking Microrheology 82
4.2.2 The Limited Role of Actomyosin Contractility in Intracellular Microrheology 86
4.2.3 Intracellular Microrheology of Endothelial Cells on a 2D Surface vs. Inside a 3D Matrix 87
4.2.4 Intracellular Microrheology of 3D Matrix-Embedded Endothelial Cells Subjected to VEGF 88
4.3 Extracellular Matrix Remodeling During Cell Motility in a 3D Matrix 89
4.3.1 The Role of Matrix Metalloproteinases in 3D Cell Motility 89
4.3.2 Particle-Tracking Matrix Traction Micromechanics 90
4.3.3 Asymmetric Patterns of Local Matrix Deformation During 3D Cell Migration 92
4.3.4 Protease Inhibitors Block Cell Motility in 3D Matrix 94
4.3.5 Local 3D Matrix Remodeling During 3D Cell Motility is Mediated by Rac1, ROCK, and Myosin II 94
4.3.6 Pseudopodial Protrusions Drive Cell Motility in 3D Through ROCK and Actomyosin Contractility 95
References 96
Chapter 5: Biophysical Properties of Scaffolds Modulate Human Blood Vessel Formation from Circulating Endothelial Colony-Forming Cells 100
5.1 Introduction 100
5.2 Concepts in Matrix Regulation of Vessel Formation 101
5.2.1 Cell Sources 101
5.2.2 Signaling Matrix–Integrin–Cytoskeleton 104
5.2.2.1 Scaffolds Used for Vasculogenesis 104
5.2.2.2 Matrix Regulation of Cell Behavior 105
5.2.2.3 Matrix Role on In Vitro Vasculogenesis/Angiogenesis 106
5.3 Review of Work 107
5.3.1 Matrix Regulation of In Vitro Endothelial Cell Network Formation 107
5.3.2 Matrix Modulation of In Vivo Vessel Formation 108
5.4 Future Directions 113
References 117
Chapter 6: Physiological and Therapeutic Vascular Remodeling Mediated by Hypoxia-Inducible Factor 1 121
6.1 Introduction 121
6.2 Vascular Responses to Hypoxia and Ischemia 123
6.3 Review of Work 125
6.4 Future Directions 130
References 130
Chapter 7: Hypoxia and Matrix Manipulation for Vascular Engineering 136
7.1 Introduction 136
7.2 Concepts in the Regulation of the Vasculature by Oxygen and the ECM 138
7.2.1 The Influence of Oxygen Tension on Vascularization 138
7.2.1.1 The In Vivo Consequences of Oxygen Gradients 139
Oxygen Availability in the Body 139
Oxygen-Sensing Mechanisms of Vascular Cells 141
7.2.1.2 Cellular Responses to Different Oxygen Concentrations 143
Metabolism and Oxygen Uptake Rate 143
Transcription of Angiogenic Genes 145
Cell Death and Survival 145
Cell Pluripotency and Differentiation 146
7.2.2 Vascular Responses to ECM 147
7.2.2.1 Types of ECM Found Participating in Vascularization 147
7.2.2.2 Properties of the ECM that Affect Vascular Morphogenesis 150
Cell Adhesion Regulates Neovascularization 151
Scaffold Degradation Regulates Vascular Morphogenesis 152
Physical Orientation of the ECM 152
Regulating Matrix Mechanics 153
7.2.3 The Effects of Oxygen Availability and the ECM 156
7.2.3.1 Varying Oxygen Tensions in the ECM of Tissue and Matrix Scaffolds: Measuring and Modeling 156
Oxygen Measurement Techniques and Challenges 156
Modeling Oxygen Transport in Tissues 157
Static Models 158
Dynamic and In Vivo Models 159
7.2.3.2 Targeted Cellular Responses to O2 Availability in Matrix Hydrogel 160
7.3 Future Directions 162
References 164
Chapter 8: Microenvironmental Regulation of Tumor Angiogenesis: Biological and Engineering Considerations 175
8.1 Introduction 175
8.2 Concepts in Tissue Engineering and Tumor Angiogenesis 177
8.2.1 Biomaterial Systems for Engineering-Based Investigations of Angiogenesis 177
8.2.2 Working Model of Tumor Angiogenesis 179
8.3 Review of Work: Biological and Engineering Considerations of Tumor Angiogenesis 181
8.3.1 Soluble Cues 181
8.3.1.1 Biological Perspective 181
Vascular Endothelial Growth Factor 181
Chemokines (IL-8) 183
8.3.1.2 Engineering Perspective 184
Temporal Control of Factor Release 185
Spatial Control of Factor Release 185
Systems to Mimic Signaling by Multiple Factors 186
8.3.2 Cell–ECM Interactions 187
8.3.2.1 Biological Perspective 187
ECM Structure and Composition 187
Integrins 187
Matrix Metalloproteinases 188
8.3.2.2 Engineering Perspective 189
Mimicry of ECM Structure and Composition 189
Presentation of Integrin Engagement Sites 190
MMP-Responsive Culture Systems 190
8.3.3 Mechanical Stimuli 191
8.3.3.1 Biological Perspective 191
Effect of Matrix Stiffness 192
External Mechanical Stimuli 192
8.3.3.2 Engineering Perspective 192
Control over Matrix Stiffness 193
Recreation of External Mechanical Stimuli 193
8.3.4 Cell–Stroma Interactions 194
8.3.4.1 Biological Perspective 194
Cell-to-Cell Contact 194
Paracrine Signaling 195
8.3.4.2 Engineering Perspective 195
Control over Direct Cell-to-Cell Contact 196
Control over Paracrine Signaling 196
8.3.5 Metabolic Stress 197
8.3.5.1 Biological Perspective 197
Hypoxia 197
Acidosis 198
8.3.5.2 Engineering Perspective 199
Control of O2 Levels in Culture 199
Monitoring of O2 Levels in Culture 200
8.4 Summary and Future Perspectives 200
References 201
Chapter 9: Microbioreactors for Stem Cell Research 211
9.1 Introduction 211
9.2 Biological Principles, Engineering Designs 213
9.2.1 Biomimetics 215
9.2.2 Bioreactors 215
9.3 Surface Patterning for Cell Coculture 216
9.3.1 Adhesive Micropatterning 216
9.3.2 Microwells 219
9.3.3 Substrate Stiffness 220
9.3.4 Microchannels 220
9.4 Microbioreactors with Perfusion 222
9.4.1 Microfluidic Systems 223
9.4.2 Microbioreactor Arrays 224
9.5 Microbioreactors with Electrical Stimulation 227
9.6 Summary 230
References 231
Chapter 10: Effects of Hemodynamic Forces on the Vascular Differentiation of Stem Cells: Implications for Vascular Graft Engineering 234
10.1 Introduction 234
10.2 Blood Vessels and Vascular Cells 234
10.3 Potential Cell Sources for Vascular Graft Engineering 235
10.3.1 Endothelial Progenitor Cells 235
10.3.2 Mesenchymal Stem Cells 236
10.3.3 Embryonic Stem Cells 236
10.4 Effects of Fluid Shear Stress on Stem Cells 238
10.4.1 Effects of Shear Stress on Endothelial Progenitor Cells 238
10.4.2 Effects of Shear Stress on Mesenchymal Stem Cells 239
10.4.3 Effects of Shear Stress on ESCs 241
10.5 Effects of Mechanical Strain on Stem Cells 242
10.5.1 Effects of Mechanical Strain on Mesenchymal Stem Cells 243
10.5.2 Effects of Mechanical Strain on Embryonic Stem Cells 243
10.6 Use of Stem Cells in Vascular Graft Engineering 244
10.7 Future Directions 246
References 246
Index 252