{"title":"Future directions for xenotransplantation in lungs.","authors":"Hidetaka Hara, Hisashi Sahara, Toyofumi Fengshi Chen-Yoshikawa","doi":"10.1097/MOT.0000000000001161","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Advancements in preclinical xenotransplant studies have opened doors for clinical heart and kidney xenotransplantation. This review assesses recent progress in lung xenotransplantation research and its potential clinical implications.</p><p><strong>Recent findings: </strong>The efficacy of the humanized von Willebrand factor in reducing platelet sequestration in ex-vivo and in-vivo lung xenotransplant models was showcased. Combining human tissue factor pathway inhibitor and CD47 expression with selectin and integrin inhibition delayed neutrophil and platelet sequestration. Enhanced expression of human complement regulatory proteins and thrombomodulin in genetically engineered pig lungs improved graft survival by reducing platelet activation and modulating coagulation disruptions. Knocking out the CMAH gene decreased antibody-mediated inflammation and coagulation activation, enhancing compatibility for human transplantation. Furthermore, CMAH gene knockout in pigs attenuated sialoadhesin-dependent binding of human erythrocytes to porcine macrophages, mitigating erythrocyte sequestration and anemia. Meanwhile, in-vivo experiments demonstrated extended survival of xenografts for up to 31 days with multiple genetic modifications and comprehensive treatment strategies.</p><p><strong>Summary: </strong>Experiments have uncovered vital insights for successful xenotransplantation, driving further research into immunosuppressive therapy and genetically modified pigs. This will ultimately pave the way for clinical trials designed to improve outcomes for patients with end-stage lung disease.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Organ Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MOT.0000000000001161","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"TRANSPLANTATION","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose of review: Advancements in preclinical xenotransplant studies have opened doors for clinical heart and kidney xenotransplantation. This review assesses recent progress in lung xenotransplantation research and its potential clinical implications.
Recent findings: The efficacy of the humanized von Willebrand factor in reducing platelet sequestration in ex-vivo and in-vivo lung xenotransplant models was showcased. Combining human tissue factor pathway inhibitor and CD47 expression with selectin and integrin inhibition delayed neutrophil and platelet sequestration. Enhanced expression of human complement regulatory proteins and thrombomodulin in genetically engineered pig lungs improved graft survival by reducing platelet activation and modulating coagulation disruptions. Knocking out the CMAH gene decreased antibody-mediated inflammation and coagulation activation, enhancing compatibility for human transplantation. Furthermore, CMAH gene knockout in pigs attenuated sialoadhesin-dependent binding of human erythrocytes to porcine macrophages, mitigating erythrocyte sequestration and anemia. Meanwhile, in-vivo experiments demonstrated extended survival of xenografts for up to 31 days with multiple genetic modifications and comprehensive treatment strategies.
Summary: Experiments have uncovered vital insights for successful xenotransplantation, driving further research into immunosuppressive therapy and genetically modified pigs. This will ultimately pave the way for clinical trials designed to improve outcomes for patients with end-stage lung disease.
期刊介绍:
Current Opinion in Organ Transplantation is an indispensable resource featuring key, up-to-date and important advances in the field from around the world. Led by renowned guest editors for each section, every bimonthly issue of Current Opinion in Organ Transplantation delivers a fresh insight into topics such as stem cell transplantation, immunosuppression, tolerance induction and organ preservation and procurement. With 18 sections in total, the journal provides a convenient and thorough review of the field and will be of interest to researchers, surgeons and other healthcare professionals alike.