Peters Marijn C, Zaldumbide Arnaud, Groeneveld Esmee J, Rabelink Martijn J W E, Peerlings Janneke H, van den Bogaerdt Antoon, Bouten Carlijn V C, Hoeben Rob C, Goumans Marie-Jose, van Wijk Abraham
Department of Pediatric Cardiothoracic Surgery, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, the Netherlands.
Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, the Netherlands.
JACC Basic Transl Sci. 2024 Sep 11;9(11):1345-1359. doi: 10.1016/j.jacbts.2024.07.003. eCollection 2024 Nov.
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.
患有心脏瓣膜缺陷的儿童一生需要多次更换供体瓣膜，因为这些瓣膜无法生长，且可能因免疫退化而导致早期失效。本研究测试了慢病毒递送病毒免疫逃避基因US2和人丝氨酸蛋白酶抑制剂9，以保护人心脏瓣膜免受免疫排斥。结果表明，我们可以有效下调心脏瓣膜细胞和完整心脏瓣膜组织中的人类白细胞抗原表达，从而降低人类白细胞抗原反应性CD8+T细胞克隆的活性，且不会诱导细胞毒性。本研究证明了人心脏瓣膜的免疫保护作用，使我们离为儿科患者提供持久的瓣膜移植更近了一步。
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