Stellate Cells in Health and Disease

1st Edition - April 8, 2015

Editors: Chandrashekhar Gandhi, Massimo Pinzani

Hardback ISBN:

9 7 8 - 0 - 1 2 - 8 0 0 1 3 4 - 9

eBook ISBN:

9 7 8 - 0 - 1 2 - 8 0 0 5 4 4 - 6

Stellate Cells in Health and Disease is a comprehensive reference providing the most up-to-date knowledge and perspectives on the function of stellate cells affecting the liver… Read more

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Stellate Cells in Health and Disease is a comprehensive reference providing the most up-to-date knowledge and perspectives on the function of stellate cells affecting the liver and other organs.

The text presents comprehensive coverage of their already established role in hepatic fibrosis along with the newer emerging evidence for stellate cell participation in the liver cell (hepatocyte) survival and regeneration, hepatic immunobiology, transplant tolerance, and liver cancer.

Chapters describe both animal and human research and the relevance of findings from animal research to human pathophysiology, and also contain sections on future directions which will be of special interest to basic and clinical researchers working on liver fibrosis, hepatic biology, and pathobiology.

Dedication
List of Contributors
Foreword
- What Have We Learned?
- The Outlook for Anti-Fibrotic Treatment
- References
Preface
Chapter 1. History and Early Work
- 1.1 Discovery of Hepatic Stellate Cells
- 1.2 HSCs and Vitamin A Homeostasis
- 1.3 Morphological Characteristics of HSCs
- 1.4 HSCs and Liver Fibrosis
- 1.5 Isolation and Culture of HSCs
- 1.6 Activation and Transdifferentiation of HSCs
- 1.7 Markers for HSCs
- 1.8 Perspective
- References
Chapter 2. Hepatic Stellate Cell Culture Models
- 2.1 Isolation of Hepatic Stellate Cells
- 2.2 Single Cell Culture
- 2.3 In Vitro- Versus In Vivo-Activated HSCs
- 2.4 Single Cell Culture and 2D: Importance of Adhesion, Arg–Gly–Asp, and Matrix Components
- 2.5 HSC Co-Cultures with Kupffer Cells, Hepatocytes, LSEC, HCC, and CC Cells
- 2.6 In Vitro 3D Culture Systems
- 2.7 Conclusions
- References
Chapter 3. Hepatic Fibrosis: A Global Clinical Problem
- 3.1 Introduction
- 3.2 Chronic Viral Hepatitis
- 3.3 NAFLD and NASH
- 3.4 Autoimmune Hepatitis, Primary Biliary Cirrhosis, and Primary Sclerosing Cholangitis
- 3.5 Etiology-Driven Liver Fibrosis
- References
Chapter 4. Stellate Cells and Hepatic Fibrosis
- 4.1 Introduction
- 4.2 Pathogenesis of Hepatic Fibrosis
- 4.3 HSCs and Hepatic Fibrosis
- 4.4 New and Emerging Pathways of HSC Activation
- 4.5 Conclusions
- References
Chapter 5. Cytokine Production and Signaling in Stellate Cells
- 5.1 Introduction
- 5.2 Platelet-Derived Growth Factor
- 5.3 Angiogenic Cytokines
- 5.4 TGF-β Superfamily
- 5.5 Chemokines
- 5.6 Tumor Necrosis Factor Superfamily
- 5.7 Interleukins and Interferons
- 5.8 Adipokines and Other Cytokines Related to Metabolism
- 5.9 Osteopontin
- 5.10 Perspective
- References
Chapter 6. Stellate Cells, Portal Myofibroblasts, and Epithelial-to-Mesenchymal Transition
- 6.1 Introduction
- 6.2 Hepatic Stellate Cells
- 6.3 Portal Fibroblasts
- 6.4 Epithelial-to-Mesenchymal Transition
- 6.5 Perspective
- References
Chapter 7. Matrix Metalloproteinases and Their Inhibitors
- 7.1 Introduction
- 7.2 The Metalloproteases (MMPs)
- 7.3 Relevance of MMP Activity and Matrix Degradation in Chronic Liver Disease
- 7.4 Conclusions
- References
Chapter 8. Stellate Cells and Portal Hypertension
- Abbreviations
- 8.1 Overview
- 8.2 Cell Culture Based Studies
- 8.3 In Vivo Studies
- 8.4 Vasoactive Mediators and Stellate Cells
- 8.5 Therapeutic Implications
- Acknowledgment
- References
Chapter 9. Hepatic Stellate Cells and Liver Cancer
- 9.1 Fibrosis and HCC
- 9.2 The Premalignant Microenvironment
- 9.3 The Tumor Microenvironment
- 9.4 HSCs as Potential Contributors to Cancer Promotion
- 9.5 Mechanisms by Which HSCs Promote HCC
- 9.6 Concluding Remarks
- References
Chapter 10. Stellate Cells in Alcoholic Hepatitis
- 10.1 Introduction
- 10.2 Pathophysiology of Fibrosis in ALD
- 10.3 HSC and ASH
- 10.4 Direct Effects of Ethanol and its Metabolites on HSC
- 10.5 Interactions of HSCs with Innate Immune Systems in ASH
- 10.6 Interactions of HSCs with Adaptive Immunity in ASH
- 10.7 Summary: Potential Therapeutic Strategies for Reducing HSC Activation in ASH
- References
Chapter 11. Hepatic Stellate Cells as Target for Reversal of Fibrosis/Cirrhosis
- 11.1 Introduction
- 11.2 Fibrosis Reversibility: General Overview
- 11.3 Mechanisms of HSC Clearance During Fibrosis Resolution
- 11.4 Control of HSC Fate and Matrix Degradation by Neighboring Liver Cells During Fibrosis Resolution
- 11.5 Conclusion
- Acknowledgments
- References
Chapter 12. Interactions of Stellate Cells with Other Non-Parenchymal Cells
- 12.1 Hepatic Stellate Cells: Introductory Remarks
- 12.2 The Crosstalk of HSCs with Macrophages
- 12.3 HSC/MFs and Interactions with Other Cells of Innate and Adaptive Immunity
- 12.4 Interactions of HSCs and HSC/MFs with LSECs: From Liver Specific Pericytes to Pro-Angiogenic Cells
- 12.5 Interactions of HSCs and Portal Fibroblasts with Cholangiocytes
- 12.6 Concluding Remarks
- References
Chapter 13. Hepatic Stellate Cells and Hepatocyte Survival
- 13.1 Introduction
- 13.2 HSC Phenotypes and Liver Injury
- 13.3 HSCs and Liver Regeneration
- 13.4 HSCs in Hepatocyte Injury During Endotoxemia
- 13.5 HSC Depletion Model to Study Acute Liver Injury
- 13.6 Perspective
- References
Chapter 14. Stellate Cells in Hepatic Immunological Tolerance
- 14.1 Hepatic Immune System
- 14.2 Liver Tolerogenicity
- 14.3 Importance of HSCs in Transplantation
- 14.4 HSCs Produce Inflammatory and Immunoregulatory Cytokines and Chemokines
- 14.5 HSC–DC Interactions
- 14.6 HSCs and Conventional Effector T Cells
- 14.7 HSCs and Regulatory T Cells
- 14.8 HSCs and NKT Cells
- 14.9 Perspective
- Acknowledgment
- References
Chapter 15. Stellate Cell Depletion Models
- 15.1 Introduction
- 15.2 Immune Cell Mediated Clearance of HM
- 15.3 HM Intrinsic Signaling Events that Limit Scar Cell Survival
- 15.4 Chemical Systems
- 15.5 Development of Carriers to Selectively Target Therapeutics to HMs
- 15.6 Advantages of HM Targeted Delivery Vehicles for Therapy
- 15.7 Nanoparticles and Viral Delivery Systems
- 15.8 Genetic Systems
- 15.9 The Role of HM Depletion in Liver Regeneration and Cancer
- 15.10 Future Perspectives
- References
Chapter 16. Pancreatic Stellate Cells
- 16.1 Introduction
- 16.2 Pancreatic Stellate Cells—Isolation and Characterization
- 16.3 Role of PSCs in Pancreatic Disease
- 16.4 PSCs in Acute Pancreatitis
- 16.5 PSCs in Chronic Pancreatitis
- 16.6 Reversal of Pancreatic Fibrosis in Chronic Pancreatitis
- 16.7 PSCs in Pancreatic Cancer
- 16.8 Summary and Conclusions
- Acknowledgments
- References
Index