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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.

Xenotransplantation: The Transplantation of Organs and Tissues Between Species

I Introduction.- 1 Introduction.- II Immunobiology of Xenograft Rejection.- 2 Hyperacute Xenograft Rejection.- 3 Role of Natural Antibody-Antigen Interactions in Xenotransplantation.- 4 Major Carbohydrate Xenotransplantation Antigens.- 5 Natural Antibody Polymorphism and Anti-Gal?1-3Gal Antibodies.- 6 Role of Complement in Xenograft Rejection.- 7 Genetic Control of Humoral Responses to Xenografts.- 8 Mechanisms of Delayed Xenograft Rejection.- 9 Anti-?galactosyl (Anti-Gal) Antibody Damage Beyond Hyperacute Rejection.- 10 Human Natural Killer Cells and Natural Antibodies Recognize Overlapping Molecular Structures on Discordant Xenogeneic Endothelium.- 11 Hemostasis in Xenotransplantation.- 12 Mechanisms of Cellular Xenograft Rejection.- 13 Human T Cell Response to Porcine Tissues.- 14 Cellular Interaction in Discordant Xenotransplantation.- 15 Immunoprivileged Sites for Alio- and Xenotransplantation.- 16 Immunobiology of Xenotransplantation in Rodents.- III Pathology of Xenograft Rejection.- 17 Histopathology of Kidney Xenograft Rejection.- 18 Histopathology of Cardiac Xenograft Rejection.- 19 Mechanism of Discordant Cardiac Xenograft Rejection - An Alternative Point of View Based on Ultrastructural Observations.- 20 Histopathology of Liver Xenotransplantation in the Nonhuman Primate.- 21 Immunopathology of Discordant Xenograft Rejection.- IV Experimental Xenotransplantation Between Closely Related Species.- 22 Experimental Concordant Kidney Xenotransplantation in Primates.- 23 Experimental Concordant Liver Xenotransplantation in Nonhuman Primates.- 24 Use of Tacrolimus (FK506) and Antimetabolites as Immunosuppressants for Xenotransplantation Across Closely Related Rodent Species.- V Experimental Xenotransplantation Between Widely Disparate Species.- 25 Roles of Anti-?Gal Antibody and Oligosaccharide Therapy in Xenotransplantation.- 26 Removal of Natural Antibodies by Immunoadsorption: Results of Experimental Studies.- 27 Neutralization of the Cytotoxic Effect of Anti-?Gal Antibodies with Monoclonal Anti-idiotypic Antibodies.- 28 Designer Tissues and Organs: Mouse to Man.- 29 Use of Anti-? Monoclonal Antibodies in Xenotransplantation: A Potential Approach To Overcome Vascular Rejection.- 30 Use of Intravenous Immunoglobulin as a Therapeutic Approach To Prevent Rejection Between Widely Disparate Species.- 31 Control of Complement-Mediated Tissue Damage by ?-Globulin: Application in Xenotransplantation.- 32 Prolongation of Discordant Xenograft Survival by Cobra Venom Factor.- 33 Therapeutic Effect of Soluble Complement Receptor Type I in Xenotransplantation.- 34 Immunobiology of Pig-to-Baboon Lung Xenotransplantation.- 35 Experimental Lung Xenografting: General Considerations.- 36 Newborn Pig-to-Baboon Cardiac Xenotransplantation: A Model of Delayed Xenograft Rejection.- 37 Total Lymphoid Irradiation: Immunosuppressive Therapy for Xenotransplantation.- 38 Xenogeneic Tolerance Through Hematopoietic Cell and Thymic Transplantation.- 39 Chimerism and Tolerance as an Approach to Xenotransplantation.- VI Experimental Pancreatic Islet Cell Xenotransplantation.- 40 Introduction.- 41 Isolated Pancreatic Islet Xenografting.- 42 Recent Approaches to the Isolation of Adult Porcine Islets of Langerhans.- 43 Xenotransplantation of Encapsulated Pancreatic Islets.- VII Pharmacologic Immunosuppression in Xenotransplantation.- 44 Pharmacologic Immunosuppressants in Xenotransplantation.- 45 Use of Brequinar Sodium To Prevent Xenograft Rejection.- 46 Leflunomide and the Malinonitriloamides in Xenotransplantation.- VIII Genetic Engineering of the Xenograft Donor.- 47 Use of Transgenic Animals as Xenotransplant Donors.- 48 Engineering of Xenografts To Provide Organs for Human Transplantation.- 49 Effect of Transgenic Expression of Human Decay Accelerating Factor on the Inhibition of Hyperacute Rejection of Pig Organs.- 50 Overcoming the Anti-Gal?(1-3)Gal Reaction To Avoid Hyperacute Rejection: Molecular Genetic Approaches.- 51 Gal?1-3Gal Xenoepitope: Donor-Targeted Genetic Strategies.- IX Aspects of Xenotransplantation in Humans.- 52 Evolutionary obstacles to xenotransplantation.- 53 Xenotransplantation and Infectious Diseases.- 54 Nucleic Acid-Based Discovery Techniques for Potential Xenozoonotic Pathogens.- 55 Comments on Ethics in Human Xenotransplantation.- X Clinical Experience.- 56 Clinical Xenotransplantation - A Brief Review of the World Experience.- 57 Extracorporeal Xenogeneic Liver Perfusion for the Treatment of Hepatic Failure.- 58 Baboon Liver Transplantation in Humans: Clinical Experience and Principles Learned.- 59 Clinical Islet Xenotransplantation.- 60 Conceptual Scientific Development of the Xenotransplantation Project in Goteborg.