Review

Authors: Tianyu Lu, Bochao Yang, Ruolin Wang...

The increasing life expectancy of humans has led to a growing numbers of patients with chronic diseases and end-stage organ failure. Transplantation is an effective approach for the treatment of end-stage organ failure; however, the imbalance between organ supply and the demand for human organs is a bottleneck for clinical transplantation. Therefore, xenotransplantation might be a promising alternative approach to bridge the gap between the supply and demand of organs, tissues, and cells; however, immunological barriers are limiting factors in clinical xenotransplantation. Thanks to advances in gene-editing tools and immunosuppressive therapy as well as the prolonged xenograft survival time in pig-to-non-human primate models, clinical xenotransplantation has become more viable. In this review, we focus on the evolution and current status of xenotransplantation research, including our current understanding of the immunological mechanisms involved in xenograft rejection, genetically modified pigs used for xenotransplantation, and progress that has been made in developing pig-to-pig-to-non-human primate models. Three main types of rejection can occur after xenotransplantation, which we discuss in detail: (1) hyperacute xenograft rejection, (2) acute humoral xenograft rejection, and (3) acute cellular rejection. Furthermore, in studies on immunological rejection, genetically modified pigs have been generated to bridge cross-species molecular incompatibilities; in the last decade, most advances made in the field of xenotransplantation have resulted from the production of genetically engineered pigs; accordingly, we summarize the genetically modified pigs that are currently available for xenotransplantation. Next, we summarize the longest survival time of solid organs in preclinical models in recent years, including heart, liver, kidney, and lung xenotransplantation. Overall, we conclude that recent achievements and the accumulation of experience in xenotransplantation mean that the first-in-human clinical trial could be possible in the near future. Furthermore, we hope that xenotransplantation and various approaches will be able to collectively solve the problem of human organ shortage.

Topics: Animals; Animals, Genetically Modified; Biomarkers; Blood Coagulation Disorders; Disease Management; Gene Expression Regulation; Graft Rejection; Graft Survival; Haplorhini; Humans; Immunity, Cellular; Immunity, Humoral; Models, Animal; Species Specificity; Swine; Translational Research, Biomedical; Transplantation Immunology; Transplantation, Heterologous

PubMed: 32038617
DOI: 10.3389/fimmu.2019.03060

Review

Authors: Sol Epstein, Michal Stuss

Transplantation provides a valuable, often life-saving, treatment for end-stage failure of many organs, including the heart, kidneys, liver, pancreas and lungs. It is also an important therapeutic option in diseases of the bone marrow and the immune system. Despite the undoubted benefits for transplant patients, it is associated with an increased risk of many complications. The potential causes include: poor general health of the patient, heavy burden of the surgery itself and the need for the long-term use of immunosuppression. In addition, the patients are also on numerous other medications, e.g. anti-coagulants, diuretics. Osteoporosis and high risk of fractures have emerged as frequent and devastating complications of the transplantation process. This article provides a review of the current literature on osteoporosis after transplantation, and the treatment options for this serious illness.

Topics: Bone Density; Fractures, Bone; Humans; Immunosuppressive Agents; Organ Transplantation; Osteoporosis; Risk Factors; Transplantation Immunology

PubMed: 22069109
DOI: No ID Found

Review

Authors: Emma M Salisbury, David S Game, Robert I Lechler...

Although transplantation has been a standard medical practice for decades, marked morbidity from the use of immunosuppressive drugs and poor long-term graft survival remain important limitations in the field. Since the first solid organ transplant between the Herrick twins in 1954, transplantation immunology has sought to move away from harmful, broad-spectrum immunosuppressive regimens that carry with them the long-term risk of potentially life-threatening opportunistic infections, cardiovascular disease, and malignancy, as well as graft toxicity and loss, towards tolerogenic strategies that promote long-term graft survival. Reports of "transplant tolerance" in kidney and liver allograft recipients whose immunosuppressive drugs were discontinued for medical or non-compliant reasons, together with results from experimental models of transplantation, provide the proof-of-principle that achieving tolerance in organ transplantation is fundamentally possible. However, translating the reconstitution of immune tolerance into the clinical setting is a daunting challenge fraught with the complexities of multiple interacting mechanisms overlaid on a background of variation in disease. In this article, we explore the basic science underlying mechanisms of tolerance and review the latest clinical advances in the quest for transplantation tolerance.

Topics: Animals; Humans; Transplantation Immunology; Transplantation Tolerance

PubMed: 24213880
DOI: 10.1007/s00467-013-2659-5

Review

Authors: Choli Hartono, Thangamani Muthukumar, Manikkam Suthanthiran...

The first successful kidney transplantation between monozygotic identical twins did not require any immunosuppressive drugs. Clinical application of azathioprine and glucocorticosteroids allowed the transfer of organs between genetically disparate donors and recipients. Transplantation is now the standard of care, a life-saving procedure for patients with failed organs. Progress in our understanding of the immunobiology of rejection has been translated to the development of immunosuppressive agents targeting T cells, B cells, plasma cells, costimulatory signals, complement products, and antidonor antibodies. Modern immunopharmacologic interventions have contributed to the clinical success observed following transplantation but challenges remain in personalizing immunosuppressive therapy.

Topics: Allografts; B-Lymphocytes; Complement System Proteins; Graft Rejection; Humans; Immunosuppressive Agents; Plasma Cells; Transplantation Immunology

PubMed: 24003247
DOI: 10.1101/cshperspect.a015487

Authors: Maria-Luisa Alegre

Topics: Humans; Organ Transplantation; Transplantation Immunology

PubMed: 32619810
DOI: 10.1016/j.cellimm.2020.104156

Review

Authors: J E Castro

Topics: Animals; Antigens, Neoplasm; Graft Rejection; Humans; Immunotherapy; Kidney Transplantation; Major Histocompatibility Complex; Neoplasms; Transplantation Immunology; Transplantation, Homologous

PubMed: 399588
DOI: 10.1093/bja/51.1.29

Review

Authors: Joren C Madsen

Topics: Heart Transplantation; Humans; Immune Tolerance; Transplantation Immunology

PubMed: 29173391
DOI: 10.1016/j.healun.2017.10.003

Review

Authors: Jordi Ochando, Zahi A Fayad, Joren C Madsen...

Consistent induction of donor-specific unresponsiveness in the absence of continuous immunosuppressive therapy and toxic effects remains a difficult task in clinical organ transplantation. Transplant immunologists have developed numerous experimental treatments that target antigen-presentation (signal 1), costimulation (signal 2), and cytokine production (signal 3) to establish transplantation tolerance. While promising results have been obtained using therapeutic approaches that predominantly target the adaptive immune response, the long-term graft survival rates remain suboptimal. This suggests the existence of unrecognized allograft rejection mechanisms that contribute to organ failure. We postulate that trained immunity stimulatory pathways are critical to the immune response that mediates graft loss. Trained immunity is a recently discovered functional program of the innate immune system, which is characterized by nonpermanent epigenetic and metabolic reprogramming of macrophages. Since trained macrophages upregulate costimulatory molecules (signal 2) and produce pro-inflammatory cytokines (signal 3), they contribute to potent graft reactive immune responses and organ transplant rejection. In this review, we summarize the detrimental effects of trained immunity in the context of organ transplantation and describe pathways that induce macrophage training associated with graft rejection.

Topics: Animals; Graft Rejection; Humans; Immune Tolerance; Immunity, Innate; Macrophages; Organ Transplantation; Transplantation Immunology; Transplantation Tolerance

PubMed: 31561273
DOI: 10.1111/ajt.15620

Authors: Guido Moll, Wai H Lim, Olaf Penack...

Topics: Histocompatibility; Transplantation Immunology

PubMed: 38558808
DOI: 10.3389/fimmu.2024.1393026

Review

Authors: Bohdan Pomahac, Ryan M Gobble, Stefan Schneeberger...

Vascularized composite allotransplantation (VCA) is a novel therapeutic option for treatment of patients suffering from limb loss or severe facial disfigurement. To date, 72 hand and 19 facial transplantations have been performed worldwide. VCA in hand and facial transplantation is a complex procedure requiring a multidisciplinary team approach and extensive surgical planning. Despite good functional outcome, courses after hand and facial transplantation have been complicated by skin rejection. Long-term immunosuppression remains a necessity in VCA for allograft survival. To widen the scope of these quality-of-life-improving procedures, minimization of immunosuppression to limit risks and side effects is needed.

Topics: Composite Tissue Allografts; Facial Transplantation; Graft Rejection; Hand Transplantation; Humans; Immunosuppression Therapy; Motor Neurons; Patient Satisfaction; Transplantation Immunology; Transplantation, Homologous; Treatment Outcome

PubMed: 24478387
DOI: 10.1101/cshperspect.a015651