Marijn C. Peters PhD , Arnaud Zaldumbide PhD , Esmee J. Groeneveld BSc , Martijn J.W.E. Rabelink BSc , Janneke H. Peerlings MSc , Antoon van den Bogaerdt MSc , Carlijn V.C. Bouten PhD , Rob C. Hoeben PhD , Marie-Jose Goumans PhD , Abraham van Wijk MD, PhD
{"title":"Immune Shielding of Human Heart Valves","authors":"Marijn C. Peters PhD , Arnaud Zaldumbide PhD , Esmee J. Groeneveld BSc , Martijn J.W.E. Rabelink BSc , Janneke H. Peerlings MSc , Antoon van den Bogaerdt MSc , Carlijn V.C. Bouten PhD , Rob C. Hoeben PhD , Marie-Jose Goumans PhD , Abraham van Wijk MD, PhD","doi":"10.1016/j.jacbts.2024.07.003","DOIUrl":null,"url":null,"abstract":"<div><div>Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen–reactive CD8+ T-cell clone without inducing cytotoxicity. This study demonstrates immune shielding of human heart valves and brings us closer to a durable valve graft in pediatric patients.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 11","pages":"Pages 1345-1359"},"PeriodicalIF":8.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC: Basic to Translational Science","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452302X24002602","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
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Abstract
Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen–reactive CD8+ T-cell clone without inducing cytotoxicity. This study demonstrates immune shielding of human heart valves and brings us closer to a durable valve graft in pediatric patients.
期刊介绍：
JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.
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