Xenotransplantation: The next quarter century

Transplantation has become a preferred therapy for the treatment of end stage organ failure, improving the quality and duration of recipients lives. The major limitation of organ transplantation is the shortage of suitable donor organs available for clinical use. Xenotransplantation using geneticall...

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Main Authors: A. Joseph Tector, Matt Tector, Rodrigo Vianna, Andrew Adams
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Transplantation Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2451959625000071
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author A. Joseph Tector
Matt Tector
Rodrigo Vianna
Andrew Adams
author_facet A. Joseph Tector
Matt Tector
Rodrigo Vianna
Andrew Adams
author_sort A. Joseph Tector
collection DOAJ
description Transplantation has become a preferred therapy for the treatment of end stage organ failure, improving the quality and duration of recipients lives. The major limitation of organ transplantation is the shortage of suitable donor organs available for clinical use. Xenotransplantation using genetically modified pig organs could provide an unlimited source of organs, allowing all patients in need to receive a transplant in a timely fashion. Xenotransplantation was limited to the experimental realm because of the presence of anti-pig antibodies that are present in the blood of every human (1, 2).The development of genetic engineering tools, especially CRISPR/Cas9 and somatic cell nuclear transfer made it possible to create pigs missing key glycan pig antigens so that the antibodies did not bind to the new pig (3-5). Preclinical results using kidneys from new donor pigs has improved to the point where nonhuman primate recipients are living for more than 4 years (Andrew Adams personal communication). The improvements in survival seen in preclinical models has led to clinical attempts at heart and kidney xenotransplantation (6, 7). Thus far in the first 5 clinical xenotransplant cases success has been modest, with only one graft (kidney) functioning past 60 days to date. The other patients receiving pig xenografts (2 hearts and 2 kidneys) succumbed to early antibody mediated rejection (AMR) (7-9). Nevertheless, the developments in preclinical and compassionate use xenotransplantation have resulted in the first FDA approved clinical trial with renal xenotransplantation. This article will deal with the issues that are likely to be the focus of the next 25 years with regards to development of clinical xenotransplantation.
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spelling doaj-art-052a43ca4c2841bc9bf36d02255e91362025-08-20T03:13:48ZengElsevierTransplantation Reports2451-95962025-06-0110210017710.1016/j.tpr.2025.100177Xenotransplantation: The next quarter centuryA. Joseph Tector0Matt Tector1Rodrigo Vianna2Andrew Adams3Department of Surgery, University of Miami School of Medicine, Miami, FL, USA; Founder Makana Therapeutics, Miami, FL, USA; Corresponding author at: Department of Surgery, University of Miami School of Medicine, Miami Transplant Institute, Miami, FL, USA.Makana Therapeutics, Miami, FL, USADepartment of Surgery, University of Miami School of Medicine, Miami, FL, USADepartment of Surgery, University of Minnesota, Minneapolis, MN, USATransplantation has become a preferred therapy for the treatment of end stage organ failure, improving the quality and duration of recipients lives. The major limitation of organ transplantation is the shortage of suitable donor organs available for clinical use. Xenotransplantation using genetically modified pig organs could provide an unlimited source of organs, allowing all patients in need to receive a transplant in a timely fashion. Xenotransplantation was limited to the experimental realm because of the presence of anti-pig antibodies that are present in the blood of every human (1, 2).The development of genetic engineering tools, especially CRISPR/Cas9 and somatic cell nuclear transfer made it possible to create pigs missing key glycan pig antigens so that the antibodies did not bind to the new pig (3-5). Preclinical results using kidneys from new donor pigs has improved to the point where nonhuman primate recipients are living for more than 4 years (Andrew Adams personal communication). The improvements in survival seen in preclinical models has led to clinical attempts at heart and kidney xenotransplantation (6, 7). Thus far in the first 5 clinical xenotransplant cases success has been modest, with only one graft (kidney) functioning past 60 days to date. The other patients receiving pig xenografts (2 hearts and 2 kidneys) succumbed to early antibody mediated rejection (AMR) (7-9). Nevertheless, the developments in preclinical and compassionate use xenotransplantation have resulted in the first FDA approved clinical trial with renal xenotransplantation. This article will deal with the issues that are likely to be the focus of the next 25 years with regards to development of clinical xenotransplantation.http://www.sciencedirect.com/science/article/pii/S2451959625000071
spellingShingle A. Joseph Tector
Matt Tector
Rodrigo Vianna
Andrew Adams
Xenotransplantation: The next quarter century
Transplantation Reports
title Xenotransplantation: The next quarter century
title_full Xenotransplantation: The next quarter century
title_fullStr Xenotransplantation: The next quarter century
title_full_unstemmed Xenotransplantation: The next quarter century
title_short Xenotransplantation: The next quarter century
title_sort xenotransplantation the next quarter century
url http://www.sciencedirect.com/science/article/pii/S2451959625000071
work_keys_str_mv AT ajosephtector xenotransplantationthenextquartercentury
AT matttector xenotransplantationthenextquartercentury
AT rodrigovianna xenotransplantationthenextquartercentury
AT andrewadams xenotransplantationthenextquartercentury