학술논문
Pig-to-human heart xenotransplantation in two recently deceased human recipients
Document Type
Article
Author
Moazami, Nader; Stern, Jeffrey M.; Khalil, Karen; Kim, Jacqueline I.; Narula, Navneet; Mangiola, Massimo; Weldon, Elaina P.; Kagermazova, Larisa; James, Les; Lawson, Nikki; Piper, Greta L.; Sommer, Philip M.; Reyentovich, Alex; Bamira, Daniel; Saraon, Tajinderpal; Kadosh, Bernard S.; DiVita, Michael; Goldberg, Randal I.; Hussain, Syed T.; Chan, Justin; Ngai, Jennie; Jan, Thomas; Ali, Nicole M.; Tatapudi, Vasishta S.; Segev, Dorry L.; Bisen, Shivani; Jaffe, Ian S.; Piegari, Benjamin; Kowalski, Haley; Kokkinaki, Maria; Monahan, Jeffrey; Sorrells, Lori; Burdorf, Lars; Boeke, Jef D.; Pass, Harvey; Goparaju, Chandra; Keating, Brendan; Ayares, David; Lorber, Marc; Griesemer, Adam; Mehta, Sapna A.; Smith, Deane E.; Montgomery, Robert A.
Source
Nature Medicine; August 2023, Vol. 29 Issue: 8 p1989-1997, 9p
Subject
Language
ISSN
10788956; 1546170X
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.