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<p>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.</p>

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Transplantation of a genetically modified porcine heart into a live human

  • 期刊论文

  • 发表日期：

    2025年1月8日

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  • Bartley P. Griffith,
  • Alison Grazioli,
  • Avneesh K. Singh,
  • Andy Tully,
  • Javier Galindo,
  • Kapil K. Saharia,
  • Aakash Shah,
  • Erik R. Strauss,
  • Patrick N. Odonkor,
  • Brittney Williams,
  • Henry J. Silverman,
  • Allen Burke,
  • Cinthia B. Drachenberg,
  • Chris L. Wells,
  • Timm Dickfeld,
  • Susie N. Hong,
  • Albert J. Hicks III,
  • Manjula Ananthram,
  • Anuj Gupta,
  • Robert H. Christenson,
  • Lo Tamburro,
  • Tianshu Zhang,
  • Alena Hershfeld,
  • Billeta Lewis,
  • Erika D. Feller,
  • Kasinath Kuravi,
  • Lori Sorrells,
  • Erwan Morgand,
  • Fariza Mezine,
  • Valentin Goutaudier,
  • Martine Rothblatt,
  • Christine L. Lau,
  • Bradley Taylor,
  • Steve Perrin,
  • Alexandre Loupy,
  • David Ayares,
  • Muhammad M. Mohiuddin

摘要

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.