Xenotransplantation is a possible solution for the shortage of tissues for human transplantation. Multiple hurdles exist to clinical xenotransplantation, including immunologic barriers, metabolic differences between pigs--the source species most commonly considered--and humans, and ethical concerns. Since clinical trials were first proposed almost 10 years ago, the degree of risk for infection transmitted from the xenograft donor to the recipient has been extensively investigated. A number of potential viral pathogens have been identified including porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), and porcine lymphotropic herpesvirus (PLHV). Sensitive diagnostic assays have been developed for each virus. Human-tropic PERV are exogenous recombinants between PERV-A and PERV-C sequences and are present in only a subset of swine. Porcine cytomegalovirus can be excluded from herds of source animals by early weaning of piglets. In contrast, the risks associated with PLHV remain undefined. Microbiologic studies and assays for potential xenogeneic pathogens have furthered understanding of risks associated with xenotransplantation. Thus far, clinical xenotransplantation of pig tissues has not resulted in transmission of viral infection to humans; significant risks for disease transmission from swine to humans have not been confirmed. If immunologic hurdles can be overcome, it is reasonable to initiate carefully monitored clinical trials.
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http://dx.doi.org/10.1111/j.1600-6143.2004.00542.x | DOI Listing |
Life Med
October 2024
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 100037, China.
Oncol Res
January 2025
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Background: Circular RNAs play an important role in regulating lung adenocarcinoma (LUAD). Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD. However, the biological mechanism of circ_0015278 in LUAD has not been fully clarified, especially in ferroptosis.
View Article and Find Full Text PDFCurr 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.
Mol Oncol
January 2025
Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Patient-derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps required to create the humanized scaffolds and achieve successful acute myeloid leukemia (AML) engraftment.
View Article and Find Full Text PDFTranspl 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.
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