LIVER REGENERATION Edited by Pedro M. Baptista Liver Regeneration Edited by Pedro M. Baptista Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Molly Kaliman Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published May, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Liver Regeneration, Edited by Pedro M. Baptista p. cm. ISBN 978-953-51-0622-7 Contents Preface IX Section 1 Cellular and Molecular Mechanisms of Regeneration 1 Chapter 1 Hepatocytes and Progenitor – Stem Cells in Regeneration and Therapy 3 Laura Amicone, Franca Citarella, Marco Tripodi and Carla Cicchini Chapter 2 Liver Progenitor Cells, Cancer Stem Cells and Hepatocellular Carcinoma 17 Janina E.E. Tirnitz-Parker, George C.T. Yeoh and John K. Olynyk Chapter 3 Hepatic Progenitors of the Liver and Extra-Hepatic Tissues 43 Eva Schmelzer Chapter 4 Possible Roles of Nuclear Lipids in Liver Regeneration 63 M. Viola-Magni and P.B. Gahan Chapter 5 Matrix Restructuring During Liver Regeneration is Regulated by Glycosylation of the Matrix Glycoprotein Vitronectin 79 Haruko Ogawa, Kotone Sano, Naomi Sobukawa and Kimie Asanuma-Date Chapter 6 The Protective Effect of Antioxidants in Alcohol Liver Damage 99 José A. Morales González, Liliana Barajas-Esparza, Carmen Valadez-Vega, Eduardo Madrigal-Santillán, Jaime Esquivel-Soto, Cesar Esquivel-Chirino, Ana María Téllez-López, Maricela López-Orozco and Clara Zúñiga-Pérez VI Contents Section 2 Animal Models of Liver Regeneration 121 Chapter 7 Analbuminemic Rat Model for Hepatocyte Transplantation 123 Katsuhiro Ogawa and Mitsuhiro Inagaki Chapter 8 Rodent Models with Humanized Liver: A Tool to Study Human Pathogens 141 Ivan Quétier, Nicolas Brezillon and Dina Kremsdorf Chapter 9 Liver Parenchyma Regeneration in Connection with Extended Surgical Procedure – Experiment on Large Animal 151 Vaclav Liska, Vladislav Treska, Hynek Mirka, Ondrej Vycital, Jan Bruha, Pavel Pitule, Jana Kopalova, Tomas Skalicky, Alan Sutnar, Jan Benes, Jiri Kobr, Alena Chlumska, Jaroslav Racek and Ladislav Trefil Section 3 Transplantation, Cell Therapies and Liver Bioengineering 175 Chapter 10 Liver Transplantation in the Clinic – Progress Made During the Last Three Decades 177 Marco Carbone,Giuseppe Orlando, Brian Sanders, Christopher Booth, Tom Soker, Quirino Lai, Katia Clemente, Antonio Famulari, Jan P. Lerut and Francesco Pisani Chapter 11 Potential of Mesenchymal Stem Cells for Liver Regeneration 189 Melisa Andrea Soland, Christopher D. Porada and Graça D. Almeida-Porada Chapter 12 Cell Based Therapy for Chronic Liver Disease: Role of Fetal Liver Cells in Restoration of the Liver Cell Functions 217 Chaturvedula Tripura, Aleem Khan and Gopal Pande Chapter 13 Liver Regeneration and Bioengineering – The Emergence of Whole Organ Scaffolds 241 Pedro M. Baptista, Dipen Vyas and Shay Soker To my family Preface This book focuses on the current knowledge regarding the physiologic processes that are triggered after hepatic injury and ultimately lead to liver regeneration. Some of these mechanisms are common to other tissues/organs, but the quickness, precision and effectiveness of liver regeneration in completely restoring its initial physiological function after injury is quite remarkable and unique among all the solid organs. Thus, the knowledge of these specific molecular and cellular mechanisms is crucial for the improvement of the current therapies and ultimately, complete recovery from liver disease. Hence, the first section of the book comprises multiple chapters that detail the mechanisms of molecular and cellular liver regeneration. Then, the second section describes different animal models used in this field of research, highlighting their significance and contribution to the study of liver regeneration. Finally, the last section presents a chapter on the gold standard for end-stage liver disease, liver transplantation, followed by numerous approaches and strategies for liver regeneration that rely on different cell therapies. The last chapter of this book describes some of the new approaches being developed that rely on tissue and organ bioengineering. It is then my hope as the book editor that this book will be able to help as many professionals and curious minds as possible, working in or out of the liver field, and that it can shed some light in the intricate mechanisms of organ regeneration. Pedro M. Baptista, Pharm.D., Ph.D. Researcher, Wake Forest Institute for Regenerative Medicine, USA [...]... throughout the whole liver lobule Collectively, these findings led to the conclusion that normal liver cell plates lack the existence of a main proliferative compartment and instead randomly distributed hepatocytes mediate normal liver turnover by slow clonal expansion without involvement of a liver stem cell (Ponder, 1996) 3 Liver regeneration The liver has an enormous capacity to regenerate by (1) replication... the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3'-methyl-4dimethylaminoazobenzene." Cancer Res 16(2): 142-148 Fausto, N (2000) "Liver regeneration. " J Hepatol 32(1 Suppl): 19-31 Fausto, N (2004) "Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells." Hepatology 39(6): 1477-1487 Fausto, N and J S Campbell (2003) "The role of hepatocytes and oval cells in liver regeneration. .. suggests their differentiation from liver stem cells (Theise et al., 1999) Since the hepatocytes are able to 4 Liver Regeneration regenerate themself to compensate liver mass loss, the existence of a liver stem cell, able to drive regeneration in conditions of extreme toxicity affecting the same hepatocytes, has long been debated Today, there is growing evidence that the liver stem cell exists and its isolation... the liver: regulation and implications for liver function" Pharmacol Ther; 53:275-354 Gebhardt, R.& Reichen J (1994) " Changes in distribution and activity of glutamine synthetase in carbon tetrachloride-induced cirrhosis in the rat: potential role in hyperammonemia" Hepatology;20:684-91 14 Liver Regeneration Grompe, M (2003) "The role of bone marrow stem cells in liver regeneration. " Seminars in liver. .. et al., 2000) 3 Liver progenitor cells and regeneration When liver parenchyma damage is particularly serious and hepatocytes are no longer able to proliferate, liver regeneration can occur through the intervention of bipotent progenitor cells that can proliferate and differentiate into hepatocytes and bile duct cells It was 1950 when Wilson and Leduc, studying the regeneration of rat liver after severe... al (2004) "Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes." Proceedings of the National Academy of Sciences of the United States of America 101(22): 8360-8365 16 Liver Regeneration Strick-Marchand, H and M C Weiss (2002) "Inducible differentiation and morphogenesis of bipotential liver cell lines from wild-type mouse... maturational liver lineage biology" Hepatology 53(3):1035-45.Ujike, K., T Shinji, et al (2000) "Kinetics of expression of connective tissue growth factor gene during liver regeneration after partial hepatectomy and D-galactosamine-induced liver injury in rats." Biochem Biophys Res Commun 277(2): 448-454 Vassilopoulos, G., P R Wang, et al (2003) "Transplanted bone marrow regenerates liver by cell fusion."... 2008) Currently, the liver transplantation is the treatment of choice for acute and chronic end-stage liver failure and for diseases refractory to other treatments; but the limited availability of donor organs is the major limiting factor in this therapeutic procedure Although different techniques of implants using either complete liver, liver reduced or hyper-reduced "split liver" (liver for two) have... non-parenchymal cells during liver regeneration (Forbes et al., 2004) The usual regeneration processes after acute and chronic liver injuries appear to rely predominantly on intrahepatic cells The most widely accepted view is that LPCs originate from liver- resident precursor or stem cells, which lie dormant and present in such low numbers as to be undetectable in normal liver However, they can be activated... (Bucher, 1963) Regeneration of the liver depends on both hyperplasia and hypertrophy of the hepatocytes, cells that in a normal adult liver exhibit a quiescent phenotype Hypertrophy begins within hours after PH then hyperplasia follows (Taub, 2004) This occurs first in the periportal region of the liver lobule then spreads toward the pericentral region (Fausto & Campbell 2003) The restoration of liver volume . LIVER REGENERATION Edited by Pedro M. Baptista Liver Regeneration Edited by Pedro M. Baptista Published by InTech. Additional hard copies can be obtained from orders@intechopen.com Liver Regeneration, Edited by Pedro M. Baptista p. cm. ISBN 978-953-51-0622-7