Transplantation of a genetically modified porcine heart into a live human.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Griffith Bartley P, Grazioli Alison, Singh Avneesh K, Tully Andy, Galindo Javier, Saharia Kapil K, Shah Aakash, Strauss Erik R, Odonkor Patrick N, Williams Brittney, Silverman Henry J, Burke Allen, Drachenberg Cinthia B, Wells Chris L, Dickfeld Timm, Hong Susie N, Hicks Albert J, Ananthram Manjula, Gupta Anuj, Christenson Robert H, Tamburro Lo, Zhang Tianshu, Hershfeld Alena, Lewis Billeta, Feller Erika D, Kuravi Kasinath, Sorrells Lori, Morgand Erwan, Mezine Fariza, Goutaudier Valentin, Rothblatt Martine, Lau Christine L, Taylor Bradley, Perrin Steve, Loupy Alexandre, Ayares David, Mohiuddin Muhammad M
Аннотация
Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen. The xenograft initially functioned well, with excellent systolic and diastolic function during the first several weeks posttransplantation. Subsequently, the xenograft developed rapidly progressing diastolic heart failure, biventricular wall thickening and, ultimately, near-complete loss of systolic function necessitating initiation of extracorporeal membranous oxygenation on day 31. Given these setbacks, the patient chose to transition to comfort care after 40 days. As with our first patient, histology did not reveal substantial immune cell infiltration but suggested capillary endothelial injury with interstitial edema and early fibrosis. No evidence of porcine cytomegalovirus replication in the xenograft was observed. Strategies to overcome the obstacle of antibody-mediated rejection are needed to advance the field of xenotransplantation.