Purpose Of Review: This review highlights advances in liver xenotransplantation, focusing on immunologic barriers and mechanisms underlying graft failure and recipient demise, and discussion of recent in-vivo results.
Recent Findings: Pig to primate models of liver xenotransplantation have been plagued by thrombocytopenia, anemia, and coagulopathy. It is now known that platelet sequestration is mediated by liver sinusoidal endothelial cells and Kupffer cells in part by asialoglycoprotein receptor 1-driven mechanisms. Xenoantigens, specifically N-glycolylneuraminic acid, play a role in graft injury as well as red blood cell consumption. Finally incompatibilities between coagulation cascade molecules contribute to lethal coagulopathy, but can be counteracted with genetic modifications and coagulation factor supplementation. Survival has markedly increased with this strategy.
Summary: An increased understanding of the cellular mechanisms responsible for failure of in-vivo pig to primate liver xenotransplant models has led to improved outcomes, and this recent success supports initial clinical application.
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http://dx.doi.org/10.1097/MOT.0000000000000578 | DOI Listing |
Curr Opin Organ Transplant
January 2025
Transplant Institute, New York University Langone Health.
Purpose Of Review: Recent advancements in genetic engineering have propelled the field of xenotransplantation from preclinical models to early compassionate use cases. As first-in-human clinical trials (FIHCTs) approach, we examine recent developments, ethical and regulatory challenges, immunological considerations, and the clinical infrastructure necessary for successful xenotransplantation trials.
Recent Findings: Expanded access transplants of pig hearts, kidneys, and livers have identified key challenges.
Front Cell Infect Microbiol
January 2025
College of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
Introduction: Coronavirus disease 2019 (COVID-19) is characterized by fever, fatigue, dry cough, dyspnea, mild pneumonia and acute lung injury (ALI), which can lead to acute respiratory distress syndrome (ARDS), and SARS-CoV-2 can accelerate tumor progression. However, the molecular mechanism for the increased mortality in cancer patients infected with COVID-19 is unclear.
Methods: Colony formation and wound healing assays were performed on Huh-7 cells cocultured with syncytia.
Transpl Int
January 2025
Division of Transplant Surgery, Department of Surgery, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United States.
Liver xenotransplantation has emerged as a potential solution to the shortage of deceased human donor organs and is now becoming a reality due to recent developments in genetic engineering and immunosuppressive therapy. Early efforts using non-human primates and genetically modified pigs faced significant challenges such as thrombocytopenia and graft rejection. Understanding the mechanism behind those challenges and using novel genetically engineered pigs enabled researchers to overcome some of the hurdles, but more research is needed.
View Article and Find Full Text PDFXenotransplantation
January 2025
Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, National Centre for Cardiovascular Disease, Department of Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Organ transplants are used to treat many end-stage diseases, but a shortage of donors means many patients cannot be treated. Xenogeneic organs have become an important part of filling the donor gap. Many current studies of kidney, heart, and liver xenotransplantation have used gene-edited pig organs on brain-dead recipients.
View Article and Find Full Text PDFXenotransplantation
January 2025
Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Advancements in xenotransplantation intersecting with modern machine perfusion technology offer promising solutions to patients with liver failure providing a valuable bridge to transplantation and extending graft viability beyond current limitations. Patients facing acute or acute chronic liver failure, post-hepatectomy liver failure, or fulminant hepatic failure often require urgent liver transplants which are severely limited by organ shortage, emphasizing the importance of effective bridging approaches. Machine perfusion is now increasingly used to test and use genetically engineered porcine livers in translational studies, addressing the limitations and costs of non-human primate models.
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