Pericyte Biology - Novel Concepts (eBook)

Alexander Birbrair received his Bachelor’s Biomedical degree from Santa Cruz State University in Brazil. He moved to North Carolina, where he finished his PhD in Neuroscience under the mentorship of Osvaldo Delbono. Then, he joined as a posdoc in Stem Cell Biology at Paul Frenette’s laboratory at Albert Einstein School of Medicine. In 2016, he was appointed faculty at Federal University of Minas Gerais in Brazil, where he started his own lab. His laboratory is interested in understanding how the cellular components of different tissues function and control disease progression. His group explores the roles of specific cell populations in the tissue microenvironment by using state-of-the-art techniques. In 2018, Alexander was elected affiliate member of the Brazilian Academy of Sciences (ABC).

Preface 5
Contents 7
Contributors 9
Chapter 1: Pericyte Biology: Development, Homeostasis, and Disease 11
References 12
Chapter 2: The NG2 Proteoglycan in Pericyte Biology 14
Introduction 15
NG2 as a Pericyte Marker 15
Mechanisms of NG2 Action 18
NG2-Dependent Aspects of Pericyte Function 18
Future Prospects 23
References 24
Chapter 3: Pericytes for Therapeutic Bone Repair 29
Introduction 30
Identification and Purification of Perivascular Cells for Bone Repair 31
Pericytes and Ectopic Bone Formation 32
Pericytes in Calvarial Defect Regeneration 33
Pericytes in Spinal Fusion 34
Pericytes for Non-union Fracture Healing 34
Discussion 35
References 37
Chapter 4: Pericyte Biology in Zebrafish 41
Early Development of the Zebrafish Vascular System 42
Zebrafish as a Model for Studying Blood Vessel Development 42
Developmental Origin of Pericytes in Zebrafish 43
Determining the Origin of Cerebral Pericytes Using Mutants and Morphants 43
Lineage Tracing of Cerebral Pericytes Using Transgenic Zebrafish 43
Developmental Origins of Trunk Pericytes 44
Determining the Origin of Trunk Pericytes Using Mutants and Morphants 44
Lineage Tracing of Trunk Pericytes Using Transgenic Zebrafish 45
Spatiotemporal Pericyte Marker Expression in the Developing Zebrafish Brain 45
Spatiotemporal Pericyte Marker Expression in the Developing Trunk Vasculature 47
Pericyte Recruitment to the Endothelium 49
Haemodynamic Forces Are Required to Recruit Pericytes to the Endothelium 49
Mural Cell Migration After Recruitment 50
Signalling Pathways Involved in Mural Cell Development, Differentiation and Recruitment 50
Sonic Hedgehog Signalling Is Required for Pericyte Development 50
TGF?/BMP Is Involved in Pericyte Development 51
Notch Signalling Regulates Mural Cell Development and Recruitment 51
PDGF Signalling Recruits Mural Cells to Vessels 52
Pericytes in Zebrafish Organs 52
Pericytes in the Zebrafish Eye 52
Mural Cells in the Visceral System 53
Mural Cell Expression in the Developing Heart 53
Zebrafish Models of Disease Involving Pericytes 53
Notch3 and CADASIL 53
Foxc1 and Foxf2 Are Involved in Mural Cell Development 54
The Role of Pericytes in Regulating Vascular Tone 54
A Novel Population of Perivascular Mural Cells in the Zebrafish Brain 55
Future Perspectives on Zebrafish Pericyte Research 56
References 56
Chapter 5: The Microvascular Pericyte: Approaches to Isolation, Characterization, and Cultivation 60
Introduction 60
Cell Isolation and Separation: Basic Considerations 61
Preparing for Pericyte Isolation 62
Digestion/Homogenization of Solid Tissues for Preparation of Single Cell Homogenates 62
Isolation of Pericytes from Single Cell Homogenates 63
Immuno-panning 63
MACS 64
Fluorescence-Activated Cell Sorting (FACS) 64
The Subculture of Pericytes from Purified Preparations of Cerebral Microvessels 65
Generation of Pericyte Lines 66
References 69
Chapter 6: Pericytes in Veterinary Species: Prospective Isolation, Characterization and Tissue Regeneration Potential 73
Introduction 74
Prospective Isolation of Pericytes from Tissues 75
Pericytes in Veterinary Species 75
Horse 76
Dog 77
Sheep 78
Pig 78
Conclusions and Future Directions 79
References 80
Chapter 7: Pericytes in the Human Vocal Fold Mucosa 84
Introduction 85
Vascular Network of the Human Vocal Fold Mucosa as a Vibrating Tissue 85
Microstructure of the Blood Vessels and Pericytes in the Human Vocal Fold Mucosa 86
Arterioles 86
Capillaries 88
Venules 89
Development of the Blood Vessels and Pericytes in the Human Vocal Fold Mucosa 90
Physiological Significances of the Vascular Network and Pericytes in the Human Vocal Fold Mucosa 91
Vascular Network in the Human Vocal Fold Mucosa 91
Pericytes in the Human Vocal Fold Mucosa 92
Deseases Related to the Vascular Network and Pericytes in the Human Vocal Fold Mucosa 93
Reinke’s Edema 93
Hemorrhage in Reinke’s Space and Vocal Fold Polyps 95
Microvascular Leisions of the Vocal Fold 95
Vocal Fold Tissue Injury 97
References 98
Chapter 8: Ca2+ Signalling in Pericytes 99
Introduction 100
Topology and Morphology of Pericytes 100
Contractility 102
Electrical Activity, Ion Currents and Channels 103
Ca2+ Signalling and Excitation-Contraction Coupling 103
VGCC-Dependent Ca2+ Entry Induced by Membrane Depolarization 104
VGCC-Dependent Intercellular Ca2+ Signalling 104
Synchronized Ca2+ Oscillations in Pericytes of Postcapillary Venules 105
Propagating Intercellular Ca2+ Waves in Ureteric Microvessels 105
Ca2+ Signalling Induced by GPCR Agonists 106
IP3R-Mediated Intracellular Ca2+ Waves and Oscillations 106
Voltage-Independent Ca2+ Entry 108
Effects of Metabolic Factors 108
Summary and Conclusions 109
References 109
Chapter 9: Pericytes Derived from Human Pluripotent Stem Cells 114
Introduction 114
Human Pluripotent Stem Cell (hPSC) Sources 115
Pericytes Derived from hPSC 116
Verification of Phenotype and In Vivo Functionality 121
Tissue Specificity and Differentiation of Mural Cell Subtypes 123
Future Directions 124
References 125
Chapter 10: Pericytes in Tissue Engineering 128
Introduction 128
Pericytes in Tissue Engineering 130
Pericytes in Bone Tissue Engineering 131
Pericytes in Cartilage Tissue Engineering 132
Pericytes in Dermal Tissue Engineering 132
Pericytes in Vascular Tissue Engineering 133
Pericytes in Cardiac Tissue Engineering 134
Pericytes in Blood Tissue Engineering 135
Future Perspective 136
References 136
Chapter 11: Pericyte Secretome 141
Introduction 143
The Pericyte Secretome Under Basal Conditions 145
The Secretome of Pericytes Under Inflammatory Conditions 146
LPS 146
IL1-?, TNF-? 152
IFN-? 152
Exposure of Brain Pericytes to Specific Pathogens (CMV, HIV, JE) 153
The Secretome of Pericytes Upon Exposure to High Glucose 154
The Secretome of Pericytes and Control of the Tumor Microenvironment 154
The Secretome of Pericytes in Angiogenesis 155
The Secretome of Pericytes Under Hypoxic Conditions 156
The Secretome of Pericytes After Other Pathological Stimuli 157
Exposure to NO 157
Exposure to Advanced Glycation Products 157
Exposure to TGF-? 158
Microvesicles and Pericytes 158
The Role of the Pericyte Secretome -Regenerative Potential 159
Future Trends 160
References 161
Correction to: The Microvascular Pericyte: Approaches to Isolation, Characterization, and Cultivation 166
Correction to: Chapter 5 in: A. Birbrair (ed.), Pericyte Biology - Novel Concepts, Advances in Experimental Medicine and Biology 1109, https://doi.org/10.1007/978-3-030-02601-1_5 166
Index 167