In recent years cell-based technologies have gained significant scientific attention, and have become a matter of intense public debate as well. Namely, (i) tissue engineering, the construction of tissues and whole organs using molecularly-designed resorbable biomaterials to create new tissue de novo with or without transplanting cells; (ii) the potential use of human embryonic stem cells for transplantation and regenerative medicine (with similar potential for adult-derived stem cells); (iii) and gene therapy, in relation with cell transplantation, have taken their places as the most discussed biomedical issues of the day. New findings in biomimetic materials, cell signalling pathways, extracellular matrix receptors and ligands, growth factors, and the human genome project are motivating the developments in these challenging research areas. This book includes manuscripts on tissue engineering, stem cells and gene therapies authored by world-renowned scientists of the field. The first section of the volume consists of four chapters giving perspectives for the current status and potential future of tissue engineering and stem cell technologies. The second section of the volume includes five chapters based on experimental and clinical data. In this section, the role of stem cells in liver tissue engineering, cell-based therapies in diabetes mellitus, and chronic degenerative diseases of the central nervous system, and adult-derived stem cell therapies are discussed. The two chapters of the third section focus on the biomarkers for tissue-engineered products, namely for tissue-engineered skin. The eight chapters of the fourth section discuss novel biomaterials developed for neural-, vascular-, aortic-, bone-, cartilage- and endocrine pancreas-tissue engineering applications. The last section of the book includes chapters on practical gene targeting applications, controlled release in gene therapy and tissue engineering, antibodies in cancer, acute-phase genes and phage-displayed peptide libraries. Proceedings of BIOMED 2002 The 9th International Symposium on Biomedical Science and Technology, held September 19-22, 2002, in Antalya, Turkey.

An up-to-date overview of blood and marrow transplantations, the book discusses in detail Indication to transplantation and pre-transplant considerations. An outlook on the latest developments and their future aspects is included, while problems and pre- and post-transplant complications are fully explored.

Despite many technological challenges faced by the xenotransplantation field, many major advances have been made in the last two decades. The field seeks to overcome the limitations and difficulties in organ procurement, which also apply to human cells and tissues, and facilitate the development of new therapies based on cell and engineered-tissue. Xenogeneic cells are simpler than solid organs and seem to pose less hurdles to attain long-term graft survival. In, Xenotransplantation: Methods and Protocols expert researchers study characterizations of xenogeneic interactions at the cellular and molecular levels and describe the use of relevant small-animal and pig-to-primate models. Related ethical and legal considerations are also covered. Written in the highly successful Methods in Molecular Biology (TM) series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Xenotransplantation: Methods and Protocols aids scientists in continuing to study xenotransplantation and its multiple aspects.

In the past few years the transplantation of organs in man has received publicity unprecedented in medical history. The first heart grafts were covered by press, radio, and television on a scal equiva lent to the news of the outbreak of a major war. Unwarranted and extravagant optimism has been followed by bitter criticism. This has undermined public confidence in the medical profession and seriously impeded progress in an important endeavour aimed at reducing human suffering. This unfortunate situation has arisen from widespread ignorance amongst the public and the medical profession of the background, present achievements, and future potential of organ grafting. Short statements by experts, frequently misquoted or cut short by television interviewers, and misinformed derogatory pronouncements by prejudiced medically qualified men, with no knowledge of the field, have produced a sorry state of confusion. It is the purpose of this book to attempt to clarify organ transplantation. The principles of organ transplantation are common to all organs but I will confine most of the discussion to transplantation of four vital organs, namely the kidney, liver, heart, and lung. ROY CALNE Cambridge January 1970 CONTENTS Preface IX List of Illustrations Xlll Acknowledgements XVll I. THE IDEA I II. THE SURGERY 7 III. REJECTION 15 IV. PREVENTION OF REJECTION 23 v. TISSUEMATCHING 39 VI. ORGAN PRESERVATION 47 VII. SUITABLE DONORS 53 VIII. ORGAN TRANSPLANTS 57 IX. ETHICS AND THE LAW 81 X."

The difference among pluripotent stem cells, multipotent stem cells, and unipotent stem cells is pointed out. Vast therapeutic applications of the following specific stem cells in disease and tissue injury are discussed: human embryonic stem cells, human mesenchymal stem cells, germ cell-derived pluripotent stem cells, induced pluripotent stem cells, human umbilical cord blood-derived stem cells, breast tumor stem cells,and hematopoietic stem cells. Because of the potential of human embryonic stem cells to produce unlimited quantities of any human cell type, considerable focus is placed on their therapeutic potential. Because of their pluripotency, these cells have been used in various applications such as tissue engineering, regenerative medicine, pharmacological and toxicological studies, and fundamental studies of cell differentiation. The formation of embryoid bodies, which are three-dimensional aggregates of embryonic stem cells, is explained as this is the first step in cell differentiation. Such embryoid body culture has been widely used as a trigger for the in vitro differentiation of embryonic stem cells. The basic capacity of self-renewal of human embryogenic stem cells is explained. The role of TGF-beta in the propagation of human embryonic stem cells is discussed. The differentiation of human embryonic stem cells into neurons, hepatocytes, cardiomyocytes, and retinal cells is fully explained. Donor policies for hematopoietic stem cells are also explained.

Advances in heart surgical treatment have been impressive in the last 15 years. In end-stage heart disease, procedures are now performed routinely which were only experimental one or two decades ago. Heart transplantation has become a well-established procedure. According to the Gen eral Registry of the International Society of Heart and Lung Transplantation. 40,738 heart transplantations had been performed through the end of 1997 with survival rates of 78 % at one year, 65 % at five years, and 42 % at ten years. The progress in this field has been due to intense efforts in understanding and modulating immune responses to the trans planted heart, to elaborate therapeutic strategies to constrain infections, and to improved out-patient care. Accordingly, heart transplantation is integrated into the facilities of the health care systems, the routine of physicians, and the awareness of patients. The resulting increase in potential organ recipients has not been met, however, by an equivalent increase of available donor organs. This increasing discrepancy has forced the technical improvement and clinical evalua tion of mechanical circulatory support systems as an option for treatment of critically ill patients with a failing heart. Initially, these assist devices were only used to maintain sufficient circulation in post-cardiotomy heart failure until myocardial function had recov ered. Since the late 1980s, their primary use has been that of bridging patients with heart failure until a suitable organ is available so that heart transplantation can be performed."

This is a time ofexcitement and progress in the field ofxenotransplantation. The work described in this book traces the development of the science of cross-spe cies transplantation, summarizes the current state ofour knowledge, and focuses on approaches directed toward future clinical application. The important question is not whether xenotransplantation will succeed, but rather how and under what circumstances xenografts will provide predictable enough results to warrant clinical application. The fact that the best results to date in clinical xenografting were achieved over three decades ago should not be a matter of discouragement, but rather a stimulus to apply new approaches to this area of work. The shortage of human organs for transplantation is cited frequently as the driving force behind the increased interest in xenotransplantation. This shortage is an undeniable fact, but there are additional potential advantages of xenotrans plantation, such as the ability to schedule replacement surgery on an elective basis and the modification of animals, organs, and tissues to improve acceptabil ity in the human host. The advances in the basic science ofxenotransplantation outlined in this book give hope that the immunologic barriers to xenotransplantation will be overcome and that transplanted organs and tissues will succeed consistently in humans. However, if our experience with human allografts provides an analogy, we may anticipate that clinical progress in xenografts will be plagued by failures and rewarded by successes, often without a complete understanding of the mechan isms involved."

Main focus of the new book will be the description and discussion of rat and mouse models for organ transplantation. Various microsurgical techniques will be presented which allow transplantation of functional organs in syngeneic systems. In particular, the extremely difficult methods necessary for organ transplantation in mice will be presented and evaluated. Besides these practical aspects the book will also cover the theoretical sides of organ transplantation like the immunobiology of allotransplantation. Special emphasis will be given to the resurgent field of xenotransplantation. The results from xenograft models developed in the recent years using rats or mice will be reviewed and their impact on future human xenotransplantation will be discussed.

MICHAEL F.A. WOODRUFF Emeritus Professor of Surgery, University of Edinburgh This book grew out of a very successful conference on Organ Transplantation held in Kuwait in December 1982. The material presented at the conference has been expanded and brought up to date, and the result is a well written and authoritative account of many aspects of organ transplantation by a distinguished team of contributors drawn from many countries. A unique feature of the book is the account it contains of the development of organ transplantation in the Middle East. Although, as yet, it has been virtually impossible in Islamic countries to take organs after death for use as transplants, it is beginning to look as if this situation may change. Meanwhile, using living volunteer donors and a small number of cadaveric organs sent from other countries, transplant teams in Kuwait and Turkey are obtaining results with kidney transplants which are as good, in terms of both transplant survival and patient survival, as those reported from acknowledged centres of excellence in the United States, Europe and other countries where organ transplantation has been established for many years.

Though kidney transplantation is considered a routine procedure, there are still significant challenges in post-transplant management. "Core Concepts in Renal Transplantation" is a clinically focused authoritative guide to the management of kidney transplantation. This comprehensive, state-of-the-art reference summarizes the recent changes in the field of transplantation, offering the complete range of up-to-date information on all the various aspects of basic immunobiology and the medical care of the transplant recipient. Written by a team of renowned authorities in renal transplantation, this concise resource is intended for both the nephrologist and the non-specialist with an interest in kidney transplantation.

Malignancies are frequent complications in organ transplantation, mainly as the result of infection with certain viruses and of long-term immunosuppression. The epidemiology confirms that the increased incidence concerns certain cancers, especially HIV-related skin cancers and EBV-related lymphoproliferative malignancies. This book covers all currently available information on this important topic of the relationships between transplantation and malignancies: preexisting cancers, posttransplant cancers, their etiology and pathophysiology, their prevention and treatment. A significant part of the volume is devoted to prophylaxis, early detection and modern forms of therapy in posttransplant lymphomas. As a conclusion of all these new data, the theory of immunosurveillance deserves to be significantly modified.

If most Americans accept the notion that the market is the most efficient means to distribute resources, why should body parts be excluded? Each year thousands of people die waiting for organ transplants. Many of these deaths could have been prevented were it not for the almost universal moral hand-wringing over the concept of selling human organs. Kidney for Sale by Owner, now with a new preface, boldly deconstructs the roadblocks that are standing in the way of restoring health to thousands of people. Author and bioethicist Mark Cherry reasserts the case that health care could be improved and lives saved by introducing a regulated transplant organs market rather than by well-meant, but misguided, prohibitions.

With contributions by D. Albrechtsen, O.H. Bentdal, H. Bondevik, I.B. Brekke, P. Fauchald, J.G. Fjeld, A. Flatmark, A. Foss, A. Hartmann, H. Holdaas, R. Innes, A. Jakobsen, N.E. Klow, B. Lien, O. Oyen, P.F. Pfeffer, K. Rootwelt, G. Sodal and K. Vatne

This volume is the work product of an international group of authors who are experienced in the field of musculoskeletal allografts. The chapters are written by experts in many differing areas of allografting and represents the current knowledge in this rapidly changing dynamic field. The reconstructive community and their patients owe a significant debt of gratitude to Doctors Czitrom and Winkler for this volume. William F. Enneking, M. D. Preface What follows is the result of a timely project bringing together the newest ideas of top experts worldwide in a rapidly growing technology: Orthopaedic Allograft Surgery. The title of the book reflects a method rather than a speciality. It transgresses well established subspecialities of orthopaedic surgery such as joint replacement, oncology, spine, trauma and sports medicine. The technology encompasses knowledge of tissue banking, biology and biomechanics, both in a research and clinical sense. The common denominator for those interested is the need and ability to provide or use allogeneic tissues in orthopaedic applications. Inherent to a multiauthored text based on chapters written by authors from many parts of the world is a variety in format and style. While we tried to some extent reducing large discrepancies, there was no attempt made to eliminate dissimilar ities. We did not aim for a homogeneous textbook. Rather, we asked for originality, novelty, individuality in the presentation of data and concepts. Consequently, chapters vary in format from that seen in a scientific article to that of a descriptive essay."

‘Jauhar weaves his own personal and family story into his history of the heart…very effectively… This gives a certain dramatic tension to the book, as it tells the fascinating and rather wonderful history of cardiology.’ –Henry Marsh, New Statesman

A Mail on Sunday Book of the Year

The heart lies at the centre of life. For cardiologist Sandeep Jauhar it is an obsession.

In this fascinating history he interweaves gripping scenes from the operating theatre with the moving tale of his family’s history of heart problems – from the death of his grandfather to the ominous signs of how he himself might die.

Jauhar looks at the pioneers who risked patients’ lives and their own careers, and confronts the limits of medical technology, arguing that how we live is more important than any device or drug we may invent. Heart is the all-encompassing story of the engine of life.

Ethical Problems in Dialysis and Transplantation presents an overview of issues with which nephrologists and decision makers are confronted in their daily practice. The search for a universal system of ethics and theories of justice are addressed. Furthermore the work provides a normative ethical discussion of ways of distributing resources with a view to selection and commercialization. Others chapters discuss a philosophical and religious analysis of stopping treatment and the clinical and ethical aspects of stopping treatment in dialysis. Different views from different countries on the subject of dialysis and transplantation are covered including the views expressed by contributors from India, Africa, Japan, Great Britain and China. The work presents the clinician with a guide to the ethical considerations underlying the treatment of dialysis and renal transplantation patients.

Clinical Management of Renal Transplantation presents The Belfast City and University Hospital experience in renal transplantation. Over the years, the Belfast Renal Transplant Unit has acquired considerable experience in all aspects of renal transplantation which have led to excellent results. The team working in the Belfast Renal Transplant Unit has built up an outstanding reputation which has become widely known. This volume is a comprehensive, practical reference work for senior medical students and nurses as well as for the established nephrologist and transplantation surgeon. It provides a clear and concise picture of the care needed by patients who are being prepared for renal transplantation or who have recently received a kidney transplant.

Is the nephrology community facilitating excess cardiovascular deaths in patients with kidney failure and anemia by treating to a subnormal hematocrit? Why have clinicians and nephrologists permitted health insurance companies and the government to decide when anemia therapy should begin in persons with progressive kidney failure? Is iron the only variable that can be manipulated to maximize response to recombinant erythropoietin? Are we using too much intravenous iron in kidney failure patients, and is oral iron supplementation worthless in sustaining iron stores during long-term erythropoietin treatment? When does left ventricular hypertrophy begin to emerge in patients with progressive renal disease and is there convincing evidence that anemia is a significant cause of LVH in this setting? Is darbepoetin alfa, a new novel, long-acting erythropoietin, really superior to recombinant erythropoietin? This book is a compilation of proceedings from a conference in Brooklyn convened to address these and other controversial and unresolved issues in renal anemia management.

This book covers all topics related to the imaging of organ transplantation. The main part of the book offers in-depth coverage of heart, renal, liver, lung, bone marrow and pancreatic and intestinal transplantation. Each of these topics is discussed firstly in a clinical chapter and then in a radiological chapter. This unique and superbly illustrated volume will be of great assistance to all who work in this field.

Kidney Transplants are the most frequently performed solid organ transplants. Pancreas transplantation offers unique survival and quality of life benefits to selected diabetics with or without concomitant renal failure. Usually, kidney and pancreas transplant recipients are managed by the same team of physicians and surgeons. Current textbooks dealing with kidney and pancreas transplantation are unfortunately usually in the form of introductory manuals or primers and lack crucial practical detail and scientific depth relevant to the practicing physician. The transplant physicians and surgeons at Cleveland Clinic have collaborated to produce a textbook devoted to kidney and pancreas transplantation that addresses the need for a work that is well grounded in scientific principles, quantitative clinical reasoning, clinical pharmacology, tested clinical practices and overall clinical applicability. Also addressed are key aspects in the initiation, maintenance and sustained growth of viable clinical programs in kidney and pancreas transplantation.

Internationally recognized scientists, clinicians, and technologists review and explain the fundamental molecular and cellular biology that has been applied to the emerging field of transplant immunology and xenotransplantation, and what impact these advances might optimally have on medicine and science. The authoritative experts writing here-many of whom made the basic discoveries underlying the recent advances-examine the biological and immunological hurdles to xenotransplantation, illuminating how the immune system interacts with the xenograft and laying a practical foundation for the use of genetic engineering and animal transplants in the treatment of human disease.

Developed by the Blood and Marrow Transplant team at Oregon Health & Science University Knight Cancer Institute, this pocket guide provides management guidelines for hematopoietic stem cell transplant patients from the moment of their initial consultation throughout the transplant process. It includes indications for transplant, essential details for patient/donor evaluation, recommendations for management of complications during and after transplant, and guidelines for long-term follow up as well as step-by-step instructions for common procedures and documentation guidelines.

An essential tool for providers, this guide presents a multidisciplinary approach to information you will need to provide quality care for your patients.

This book deals with organ failure and the way it can be managed artificially without requiring a transplant. Written by a mixture of European and US physicians and surgeons, each of the chapters compares the artificial organ to what is currently available from the transplant point of view to highlight the current and modern available techniques for organ replacement.

The book will be a useful reading for postgraduate students and people interested in modern surgical and medical technology.

MSC (mesenchymal stem cells) have been reported to initiate revascularization after injury, to facilitate engraftment of blood-forming stem cells, and to reduce the incidence of graft-vs. host disease through their immune-suppressive qualities. Finally, bone marrow-derived MSC have been reported to home to areas of solid tumor revascularization, and thus may be used as delivery vehicles to target ablative agents into dividing tumor cells. Recently the characteristics of human MSC from adipose (fat) tissue have also been identified. The possibility of repairing tissues, speeding stem cell engraftment, and targeting solid tumors for specific killing, using MSC easily harvested from bone marrow, or better yet, from unwanted fat tissue, holds broad appeal, and is an intriguing possibility that could have dramatic effect on health care.

This book has information on how to isolate, grow, and characterize MSC from marrow and fat, and gives important insight into how these cells may be used for gene delivery and cellular therapies in the future. Updates on emerging clinical trials are given.

Surgical Management of Heart Failure brings together the current knowledge on the surgical management of heart failure into one volume. It is designed to have copious illustrations and photographic material that will explain the techniques and surgical management of patients with heart failure in an effective modern format.