Pig-to-human heart xenotransplantation in two recently deceased human recipients

Nader Moazami, Jeffrey M. Stern, Karen Khalil, Jacqueline I. Kim, Navneet Narula, Massimo Mangiola, Elaina P. Weldon, Larisa Kagermazova, Les James, Nikki Lawson, Greta L. Piper, Philip M. Sommer, Alex Reyentovich, Daniel Bamira, Tajinderpal Saraon, Bernard S. Kadosh, Michael DiVita, Randal I. Goldberg, Syed T. Hussain, Justin ChanJennie Ngai, Thomas Jan, Nicole M. Ali, Vasishta S. Tatapudi, Dorry L. Segev, Shivani Bisen, Ian S. Jaffe, Benjamin Piegari, Haley Kowalski, Maria Kokkinaki, Jeffrey Monahan, Lori Sorrells, Lars Burdorf, Jef D. Boeke, Harvey Pass, Chandra Goparaju, Brendan Keating, David Ayares, Marc Lorber, Adam Griesemer, Sapna A. Mehta, Deane E. Smith, Robert A. Montgomery

Research output: Contribution to journalArticlepeer-review

Abstract

Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours. Although both xenografts demonstrated excellent cardiac function immediately after transplantation and continued to function for the duration of the study, cardiac function declined postoperatively in one case, attributed to a size mismatch between the donor pig and the recipient. For both hearts, we confirmed transgene expression and found no evidence of cellular or antibody-mediated rejection, as assessed using histology, flow cytometry and a cytotoxic crossmatch assay. Moreover, we found no evidence of zoonotic transmission from the donor pigs to the human recipients. While substantial additional work will be needed to advance this technology to human trials, these results indicate that pig-to-human heart xenotransplantation can be performed successfully without hyperacute rejection or zoonosis.

Original languageEnglish (US)
Pages (from-to)1989-1997
Number of pages9
JournalNature Medicine
Volume29
Issue number8
DOIs
StatePublished - Aug 2023

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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