Biology of Pericytes – Recent Advances (Stem Cell Biology and Regenerative Medicine, 68)

Pericytes were originally discovered and named more than hundred years ago as contractile cells around the blood vessel endothelial cells. Due to the lack of exclusive markers, pericytes are now defined by a combination of location, morphology and gene expression. Pericytes are attracting increasing attention as important regulators during development and during normal and disturbed organ function. In recent years, remarkable progress has been made in the identification and characterization of pericytes subpopulations and their amazing functions using state-of-art techniques. These advantages facilitated identification of molecular basis of interaction between these cells with several other more well studied cell types, and revealed key signals derived from pericytes involved in homeostasis, regeneration, and disease regulation. In the last ten years, several unexpected roles of pericytes have been discovered. It has been demonstrated that pericytes from different tissues differ in their properties as well as functions. Even more, pericytes are heterogeneous also within the same organ. This book is will describe the major contributions of pericytes to different organs biology in physiological and pathological conditions. The book will teach the readers about this so special cell type that 10 years ago was almost completely forgotten, and it was associated basically only with vascular stability. Recently, it become a very hot topic to work in. Several articles in Nature, Science and Cell have been and are being currently published about this cell type. These recent works are revealing how important those cells are for before unimaginable biological processes. Thus, this book will update us on what are the most novel functions attributed to these cells. Also, will introduce to the young generation all the history about these cells from when they were discovered in different organs till where we are now in this field. So it will be a great book for both cell biology students as well as researchers that will have an update on these cells biology in different organs. Preface Contents About the Editor Chapter 1: In Vivo Optical Imaging and Manipulation of Brain Pericytes 1.1 Introduction 1.2 Identifying Brain Pericytes 1.3 Distinct Functions of Pericyte Subtypes 1.4 Targeting Brain Pericytes for In Vivo Imaging 1.4.1 Cre/Lox System for Genetic Targeting of Pericytes 1.4.2 PDGFRβ-Cre 1.4.3 NG2-Cre, NG2-CreER, and NG2-DsRed 1.4.4 Tbx18-CreERT2 1.4.5 Myh11-CreERT2 1.4.6 Pericyte-CreER 1.4.7 Fluorescent Reporters and Actuators 1.4.8 Viral Targeting of Brain Pericytes 1.4.9 In vivo Dye Labeling of Brain Pericytes 1.5 Visualization of Brain Pericytes In Vivo 1.5.1 Cranial Windows for in vivo Multi-Photon Imaging 1.5.2 Acute Cranial Window 1.5.3 Thinned-Skull Window 1.5.4 Chronic Cranial Window 1.5.5 Anesthesia during Surgery and Imaging 1.5.6 Head-Mounting/Stabilization 1.5.7 In vivo Two-Photon Microscopy 1.5.8 Physiological Variables 1.5.9 I.v. Dyes as Vascular Labels 1.5.10 I.v. Dyes as Vascular Permeability Probes 1.5.11 Vascular Characteristics and Dynamics 1.6 In Vivo Observation of Pericyte Structure and Function 1.7 In Vivo Manipulation of Pericytes 1.7.1 Genetic Pericyte Ablation 1.7.2 Two-Photon Pericyte Ablation 1.7.3 Two-Photon Optogenetic Manipulation of Pericytes 1.8 Concluding Remarks References Chapter 2: The Complex and Integral Roles of Pericytes Within the Neurovascular Unit in Health and Disease 2.1 Pericytes Reside in the Brain’s Microvasculature 2.2 Pericytes Are a Central Part of the Neurovascular Unit 2.2.1 Physical Pericyte-Endothelial Cell Interactions 2.2.2 Pericyte-Endothelial Cell Communication 2.2.3 Pericyte-Astrocyte Communication 2.2.4 Pericyte-Neuron Communication 2.3 Functions of Pericytes in the Neurovascular Unit 2.3.1 Experimental Methods to Reduce Pericyte Numbers in vivo 2.3.2 The Role of Pericytes in the Regulation of Cerebral Blood Flow 2.3.3 The Role of Pericytes in Vascular Development and Angiogenesis 2.3.4 The Role of Pericytes in Vascular Stability 2.3.5 The Role of Pericytes in Blood-Brain Barrier Maintenance 2.3.6 The Role of Pericytes in Neuroinflammation 2.3.7 Pericytes and Their Stem Cell Potential 2.4 Pericytes in Neurological Diseases 2.4.1 The Role of Pericytes in Stroke 2.4.2 The Role of Pericytes in Alzheimer’s Disease 2.4.3 The Role of Pericytes in Amyotrophic Lateral Sclerosis 2.4.4 The Role of Pericytes in Multiple Sclerosis 2.4.5 The Role of Pericytes in Other Neurological Diseases 2.4.6 The Role of Pericyte Subtypes in Neurological Disease 2.5 Are Pericytes in the Brain Different to Pericytes in the Periphery? 2.6 Future Opportunities in Brain Pericyte Research 2.6.1 Therapeutically Targeting Pericytes 2.6.2 Pericyte Biomarkers of Neurological Disease 2.6.3 Therapeutic Administration of Pericytes 2.7 Conclusion References Chapter 3: Biology of Pericytes – Recent Advances: Role of Pericytes in Brain Metastasis 3.1 Introduction 3.2 Basic Role of Pericytes in Brain Metastasis 3.3 In vitro BBB Model 3.4 Differentially Expressed Genes of Pericytes in Brain Metastasis 3.4.1 Pericyte Origins and Molecular Markers 3.4.2 Cancer-Associated Fibroblasts (CAFs), Angiogenesis, and Pericytes 3.4.3 Angiogenesis Patterns and Pericytes 3.4.4 Angiotropism/PM/EVMM and Pericytes 3.4.5 Immune Evasion in the Tumor Microenvironment and Pericytes 3.5 Pericyte and Regenerative Medicine 3.5.1 Pericytes Represent One Origin of Neural Stem/Progenitor Cells After Ischemic Stroke 3.5.2 Pericytes in Brain Tumors 3.5.3 Pericytes and Regenerative Medicine in Brain Tumor 3.6 Summary References Chapter 4: Effects of Cytomegalovirus on Pericytes 4.1 Introduction 4.2 Cytomegalovirus Biology 4.3 Pericytes 4.4 Cytomegalovirus and Vascular Disease 4.4.1 Cytomegalovirus Infection of Pericytes in the Neurovascular Unit 4.4.2 Cytomegalovirus Infection of Pericytes in Retinal Vascular Unit 4.4.3 Cytomegalovirus Infection of Mesangial Cells: Pericytes of the Glomerular Vascular Unit 4.4.4 Cytomegalovirus Infection of Pericytes in at the Placental Vascular Barrier 4.4.5 Cytomegalovirus Infection of Pericytes in Adipose Vasculature 4.5 Discussion and Conclusions References Chapter 5: Pericytes in Retinal Ischemia 5.1 Pericytes Regulate Microcirculatory Blood Flow in the Retina 5.2 Retinal Pericytes Are Vulnerable to Ischemia 5.3 Mechanisms of Ischemia-Induced Pericyte Contractions 5.4 Incomplete Microcirculatory Reflow After Central Retinal Artery Recanalisation 5.5 Pericytes and Blood-Retina Barrier Leakiness in Retinal Ischemia 5.6 Pericytes and Angio- and Neuro-genesis Following Retinal Ischemia 5.7 Diabetic Retinopathy 5.8 Future Directions References Chapter 6: Inflammatory Mediators Released by Brain Pericytes as Sensors and Effectors in Blood-Brain Barrier Dysfunction 6.1 Introduction 6.2 Intercellular Communication Between Brain Pericytes and Other Cell Types in the Neurovascular Unit in Health and Disease 6.3 Extracellular Molecules as Pericyte Activators 6.4 Identification of Activated Brain Pericytes Associated with BBB Dysfunction 6.5 Conclusion and Perspective References Chapter 7: TLR-4 Signaling in Pericytes 7.1 Introduction 7.1.1 The Heterogeneity of Pericytes 7.1.2 The Main Sensor of LPS: The TLR-4 7.1.3 The Molecular Mechanisms of Pericytes in Sepsis: TLR-4 Immunomodulation 7.1.4 Pericytes and TLR-4 Signaling in Cardiac Diseases: From Inflammation to Fibrosis? 7.1.5 Pericytes in Lung Diseases: From Sentinel of Immune Response to Mediators of Fibrosis 7.1.6 Pericytes in Neurovascular Diseases and the Impact of TLR-4 Signaling 7.1.7 Pericytes in Renal Diseases: From Inflammation to Fibrosis 7.2 Conclusions References Chapter 8: EphA7+ Multipotent Pericytes and Their Roles in Multicellular Organisms 8.1 Mutent Cells Within the Microvasculature 8.1.1 Are MPCs the Major MSCs? 8.1.2 Identification of Novel Multipotent PCs Using an Immortalized PC Line Library 8.2 Role of EphA7+ PCs in the Multicellular Organisms 8.2.1 Angiogenesis: Do EphA7+ PCs Function as Capillary Progenitor Cells? 8.2.2 Neurogenesis: Do EphA7+ PCs Play a Central Role in Nerve Vessel Wiring? 8.2.3 Myogenesis: Do EphA7+ PCs Have Self-Regenerative Potency? 8.3 Future Perspectives on MPCs Research 8.3.1 Specificities of PC-Markers 8.3.2 Regulators of MPCs Function 8.3.3 Transgenic Animal Models Targeting MPCs References Chapter 9: Skeletal Muscle-Resident Pericyte Responses to Conditions of Use and Disuse 9.1 Skeletal Muscle Mononuclear Cells 9.2 Skeletal Muscle Pericytes 9.3 Pericyte Contribution to Skeletal Muscle Development and Injury 9.4 Impact of Skeletal Muscle Use (Contraction) on Pericyte Function 9.5 Impact of Skeletal Muscle Disuse on Pericyte Function 9.6 Conclusions and Future Directions References Chapter 10: Pericytes in Myocardial Diseases 10.1 Introduction 10.2 Characteristics of Cardiac Pericytes 10.3 The Role of Pericytes in Cardiac Homeostasis 10.4 The Role of Pericytes in Myocardial Disease 10.4.1 Pericytes in Myocardial ischemia and Infarction 10.4.1.1 The Cell Biology of Cardiac Repair: From Inflammation to Fibrosis 10.4.1.2 Pericytes in the Inflammatory Phase of Cardiac Repair (Fig. 10.2) 10.4.1.3 The Role of Pericytes in the Pathogenesis of No-Reflow 10.4.1.4 The Contribution of Pericytes in Fibroblast Activation Following Myocardial Infarction (Fig. 10.3) 10.4.1.5 Pericytes During the Maturation Phase of Cardiac Repair 10.4.2 Pericytes in Chronic Heart Failure 10.4.2.1 Pericytes in Diabetic Cardiomyopathy 10.5 Pericytes as Therapeutic Targets in Myocardial Disease 10.6 Conclusions and Future Directions References Chapter 11: Adventitial and Skeletal Muscle Pericytes in Health and Ischemic Tissue Regeneration 11.1 Introduction 11.2 Adventitial Pericytes 11.2.1 Introduction 11.2.2 A Brief Definition of Adventitial ‘Pericyte-Like’ Populations 11.2.3 Adventitial Pericytes in Pathology 11.2.4 Adventitial Pericytes in Repair 11.2.5 Adventitial Pericytes in Tissue Engineering 11.3 Skeletal Muscle Pericytes 11.3.1 Introduction 11.3.2 Skeletal Muscle Pericytes in Muscle Development and Homeostasis 11.3.3 Skeletal Muscle Pericytes in Diabetes and Critical Limb Ischemia 11.3.4 Skeletal Muscle Pericytes in Regeneration and Regenerative Medicine 11.4 Future Perspectives References Index