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It is thirty years since the technique of high-yield preparation of isolated hepatocytes, by collagenase perfusion of the liver, was published. The original method described by Berry and Friend has undergone many minor modifications by other workers, and the two-step procedure introduced by Seglen in 1976 has become the most frequent way to prepare hepatocyte suspensions. An important development introduced by Bissell in 1973 was the use of the cells as the first step in monolayer culture. The availability of the isolated hepatocyte preparation as cells in suspension or culture has undoubtedly facilitated research on the liver. This was emphasised in our book, published (with Dr. Greg Barritt) in 1990, which described in detail methods of preparation and the properties of the isolated hepatocytes. It also discussed the usefulness of the preparation for the study of intermediary and xenobiotic metabolism, calcium ion transport, and the growth and differentiation of hepatocytes in culture. The book also touched briefly on a range of specialised techniques, including peri fusion, subcellular fractionation, transplantation, cryopreservation and measurement of intracellular pH. Although standard procedures for the manipulation of hepatocytes have not changed a great deal in ten years, they have undoubtedly been refined. This applies particularly to hepatocyte culture techniques, cryopreservation, and even to preparation of hepatocyte suspensions, where it is now feasible to use purified enzymes. There is also much more emphasis on the use and study of human hepatocytes, particularly in the field of pharmacology and therapeutics.
It is thirty years since the technique of high-yield preparation of isolated hepatocytes, by collagenase perfusion of the liver, was published. The original method described by Berry and Friend has undergone many minor modifications by other workers, and the two-step procedure introduced by Seglen in 1976 has become the most frequent way to prepare hepatocyte suspensions. An important development introduced by Bissell in 1973 was the use of the cells as the first step in monolayer culture. The availability of the isolated hepatocyte preparation as cells in suspension or culture has undoubtedly facilitated research on the liver. This was emphasised in our book, published (with Dr. Greg Barritt) in 1990, which described in detail methods of preparation and the properties of the isolated hepatocytes. It also discussed the usefulness of the preparation for the study of intermediary and xenobiotic metabolism, calcium ion transport, and the growth and differentiation of hepatocytes in culture. The book also touched briefly on a range of specialised techniques, including peri fusion, subcellular fractionation, transplantation, cryopreservation and measurement of intracellular pH. Although standard procedures for the manipulation of hepatocytes have not changed a great deal in ten years, they have undoubtedly been refined. This applies particularly to hepatocyte culture techniques, cryopreservation, and even to preparation of hepatocyte suspensions, where it is now feasible to use purified enzymes. There is also much more emphasis on the use and study of human hepatocytes, particularly in the field of pharmacology and therapeutics.
Liver Pathophysiology: Therapies and Antioxidants is a complete volume on morphology, physiology, biochemistry, molecular biology and treatment of liver diseases. It uses an integral approach towards the role of free radicals in the pathogenesis of hepatic injury, and how their deleterious effects may be abrogated by the use of antioxidants. Written by the most prominent authors in the field, this book will be of use to basic and clinical scientists and clinicians working in the biological sciences, especially those dedicated to the study and treatment of liver pathologies. - Presents the most recent advances in hepatology, with a special focus on the role of oxidative stress in liver injury. - Provides in vivo and in vitro models to study human liver pathology. - Explains the beneficial effects of antioxidants on liver diseases. - Contains the most recent and modern treatments of hepatic pathologies, including, but not limited to, stem cells repopulation, gene therapy and liver transplantation.
Stem Cells and Cancer in Hepatology: From the Essentials to Application offers basic scientists and clinicians in the fields of stem cells, hepatology and oncology an overview of the interaction between liver biology, stem cells and cancer. It discusses how the liver performs regeneration and repair, the role stem cells play in these processes, and the mechanisms by which liver cancers are initiated and developed. As the field of stem cells and cancer stem cells in hepatology is new and dynamic, thus making it difficult for researchers and clinicians to understand the most relevant historic and novel studies, this volume addresses that challenge.
Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.
In recent years there has been an increasing need for transplantation, but the number of donor livers available has increased only slightly, despite intensive public relations activities. New concepts in the field of transplantation, for instance the transplantation of living donor organs or the splitting of organs, are urgently required, to safeguard the treatment of patients with severe liver disease. The development and clinical application of cell therapy for patients with liver disease could soon present a significant enhancement of the therapeutic options. The aim of such cell therapy is to repair or improve the biological function of the chronically and acutely damaged liver. Even though systematic trials are not available, individual case reports and small series already show promising clinical results. Present concepts of cell therapy for liver diseases based on the use of primary hepatocytes have recently been considerably extended through new data on the biology of stem cells. The adult haematopoetic stem cell as a pool for hepatocyte grafts - what would be the perspectives for the clinical application? This book is the proceedings of the Falk Symposium No. 126 on `Hepatocyte Transplantation' (Progress in Gastroenterology and Hepatology Part III) held in Hannover, Germany, October 2-3, 2001, and is a forum for basic research, but also for questions concerning clinical applications in the field of hepatocyte transplantation.
Chronic liver failure is a frequent condition in clinical practice that encompasses all manifestations of patients with end-stage liver diseases. Chronic liver failure is a multiorgan syndrome that affects the liver, kidneys, brain, heart, lungs, adrenal glands, and vascular, coagulation, and immune systems. Chronic Liver Failure: Mechanisms and Management covers for the first time all aspects of chronic liver failure in a single book, from pathogenesis to current management. Each chapter is written by a worldwide known expert in their area and all provide the latest state-of-the-art knowledge. This volume is specifically designed to provide answers to clinical questions to all doctors dealing with patients with liver diseases, not only clinical gastroenterologists and hepatologists, but also to internists, nephrologists, intensive care physicians, and transplant surgeons.
Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.
This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
Hepatocytes account for approximately 80% of the liver mass and play a significant role in various aspects of liver physiopathology, exhibiting unrivaled complexity and diversity of functions. In Hepatocytes: Methods and Protocols, expert researchers provide the reader with methods, technical protocols, and review chapters focusing on selected areas of hepatocyte biology including isolation, culture, differentiation and stem cells, and hepatocyte use in clinical, basic, and applied research. With a specific emphasis on human hepatocytes, the volume presents chapters covering subjects including hepatocyte culture models, cryopreservation methods, differentiation assessment, liver ontogenesis, production of hepatocytes from stem cells, drug/xenobiotic metabolism, toxicity and transport, bile acid and blood coagulation factor production, infection by HBV and HCV, humanized animals, biortificial liver devices, hepatocyte transplantation. As a volume in the highly successful Methods in Molecular BiologyTM series, protocol chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Hepatocytes: Methods and Protocols will be useful to all those who are currently using or planning to use human, or animal, hepatocytes to investigate any aspect of liver physiopathology or who are interested in liver development or liver stem cells and liver biotherapy.