Liver Regeneration (eBook)

Dieter Häussinger (Herausgeber)

eBook Download: PDF

2011
232 Seiten
De Gruyter (Verlag)
978-3-11-025079-4 (ISBN)

Infos

Understanding the mechanisms involved in liver regeneration is of crucial importance for clinical medicine, not only regarding carcinogenesis and diabetes treatment, but also for the use of stem cells for cell therapy and liver surgery. This graduate-level text provides an overview of the current state of knowledge of the molecular mechanisms of liver regeneration. Hepatic stem cells are introduced and the important players involved in regeneration such as oval cells, bone marrow and stellate cells are reviewed. The cell signaling pathways that initiate liver regeneration and regulate the switch between proliferation and apoptosis are presented and the role of liver stem cells in tumorigenesis is discussed. The book also treats the epigenetic regulation of liver stem cells and the roles of inflammation and angiogenesis in liver regeneration. This compact overview of the fascinating regenerative capacity of the liver will be of interest to graduate students and post-docs in molecular biology, biochemistry and medicine.

Dieter Häussinger, Heinrich Heine University, Düsseldorf, Germany.

Autor

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Dieter Häussinger, Heinrich Heine University, Düsseldorf, Germany.

Inhalt

Preface 6
Contents 8
Author Index 12
Abbreviations 16
1 Liver Regeneration and Partial Hepatectomy: Process and Prototype 20
1.1 Introduction 20
1.2 Liver Regeneration: Historical Perspective 20
1.3 Partial Hepatectomy as a Means to Study Liver Regeneration 21
1.4 Three Phases of Liver Regeneration after Partial Hepatectomy 23
1.5 Future Directions 29
2 Oval Cells, Bone Marrow, and Liver Regeneration 36
2.1 Stem Cells: Definition and Properties 36
2.2 Liver Stem Cells and Their Role in Hepatic Regeneration 40
2.3 Extrahepatic Stem Cells with Hepatogenic Potential: “The Blood of Prometheus” 44
2.4 Clinical Applications of Bone Marrow–Derived Stem Cells in Hepatology 49
3 Inflammation and Liver Regeneration 58
3.1 Introduction 58
3.2 Liver Regeneration and Inflammation: General Aspects 59
3.3 Liver Macrophages and Their Relevance for Liver Regeneration 60
3.4 Inflammatory Mediators Are Required to Promote Liver Regeneration 63
3.5 Inappropriate Inflammation Impairs Liver Regeneration 65
3.6 Role of NK and NKT-cells for Liver Regeneration: Negative Regulators of Regeneration 66
4 Lymphotoxin ? Receptor and Tumor Necrosis Factor Receptor p55 in Liver Regeneration 72
4.1 The TNF/TNFR Superfamily 72
4.2 Liver Regeneration 75
4.3 TNFRp55 and Liver Regeneration 76
4.4 LTßR and Liver Regeneration 77
5 The Hepatic Stem Cell Niches 82
5.1 Introduction 82
5.2 Secreted Factors in the Stem Cell Niche 83
5.3 Physical Contacts of Stem Cells with Their Niche 90
5.4 Identification of Stem Cell Niches 91
5.5 Stem Cell Niches in the Liver 93
6 Stellate Cells in the Regenerating Liver 104
6.1 Characterization of Stellate Cells 104
6.2 Plasticity of Hepatic Stellate Cells 109
6.3 Stellate Cells in Liver Regeneration 109
7 Epigenetics during Liver Regeneration 118
7.1 Definition and Mechanisms of Epigenetics 118
7.2 Methods to Investigate Epigenetic Mechanisms 122
7.3 Epigenomics in Liver Regeneration 123
7.4 Epigenetics During Stellate Cell Activation 124
8 Hedgehog Signaling and Liver Regeneration 130
8.1 Introduction 130
8.2 Liver Regeneration after Partial Hepatectomy 131
8.3 Fetal Development of the Liver 131
8.4 Overview of Hedgehog Signaling Pathway 132
8.5 Reactivation of the Hedgehog Pathway after Partial Hepatectomy 134
8.6 Hedgehog Pathway Activation during Repair of Chronic Liver Injury: General Concepts 135
8.7 Hedgehog Pathway Activation and Liver Progenitors in Chronic Injury Models 136
8.8 Hedgehog Pathway Activation and Liver Fibrosis 137
8.9 Hedgehog Pathway Activation and Vascular Remodeling in Injured Livers 140
8.10 Hedgehog Pathway Activation and Hepatocarcinogenesis 140
9 EGFR, CD95, and the Switch between Proliferation and Apoptosis in Hepatic Stellate Cells 148
9.1 Introduction 148
9.2 Liver Cell Proliferation Involves Ligand-dependent EGFR Activation 149
9.3 Liver Cell Apoptosis Involves EGFR-dependent CD95 Activation 151
9.4 EGFR Activation Can Couple to Both Proliferation and Apoptosis in Hepatic Stellate Cells 154
10 Angiogenesis and Liver Regeneration 164
10.1 Introduction 164
10.2 Blood Flow and Cell Types in the Adult Liver 164
10.3 Angiogenesis in Liver Regeneration 167
10.4 Importance of VEGF for Liver Regeneration 169
10.5 Role of Angiogenesis in Liver Damage/Disease 170
10.6 Questions and Problems 172
11 A Quantitative Mathematical Modeling Approach to Liver Regeneration 178
11.1 Definition 178
11.2 Methods to Quantify Spatial–Temporal Information in Liver Lobules 180
11.3 Normal Liver Lobule: The Reference State 182
11.4 Quantifying the Regeneration Process: Process Parameters 183
11.5 Mathematical Model 183
11.6 Simulation Results with the Mathematical Model 188
11.7 Limitations 190
12 Animal Models for Studies on Liver Regeneration 194
12.1 Introduction 194
12.2 Different Types of Regenerative Processes 194
12.3 Different Types of Animal Models 196
12.4 Surgical Animal Models 198
12.5 Pharmacological Models 199
12.6 Transgenic Models 200
12.7 Immunological Models 205
13 Therapeutic Potential of Bone Marrow Stem Cells in Liver Surgery 210
13.1 Clinical Scenario 210
13.2 Mechanisms of Hepatic Regeneration 211
13.3 Stem Cells in Liver Regeneration 211
13.4 Mesenchymal or Hematopoietic Stem Cells to Support Liver Regeneration? 212
13.5 BMSC as External Conductors of Liver Regeneration 213
13.6 Stem Cell Treatment in Chronic Liver Disease in Humans 213
13.7 BMSC to Support Liver Proliferation Prior to Hepatectomy 214
Index 226

Produkt-Details

• Erscheint lt. Verlag: 7.7.2011
• Reihe/Serie: De Gruyter Textbook
• Zusatzinfo: 51 col. ill., 7 b/w tbl.
• Verlagsort: Berlin/Boston
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Technik
• Schlagworte: Biochemie • biochemistry • Leber • Liver • Molecular Biology • Molekularbiologie • Regeneration • Therapie • therapy
• ISBN-10: 3-11-025079-9 / 3110250799
• ISBN-13: 978-3-11-025079-4 / 9783110250794