The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation

Bibliographic Details
Title: The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation
Authors: S. A. Sanatkar, K. Kinoshita, A. Maenaka, H. Hara, D. K. C. Cooper
Source: Transplant International, Vol 37 (2025)
Publisher Information: Frontiers Media S.A., 2025.
Publication Year: 2025
Collection: LCC:Specialties of internal medicine
Subject Terms: immunosuppression, xenotransplantation, transplantation immunology, swine, non-human primate, Specialties of internal medicine, RC581-951
More Details: An overview is provided of the evolution of strategies towards xenotransplantation during the past almost 40 years, focusing on advances in gene-editing of the organ-source pigs, pre-transplant treatment of the recipient, immunosuppressive protocols, and adjunctive therapy. Despite initial challenges, including hyperacute rejection resulting from natural (preformed) antibody binding and complement activation, significant progress has been made through gene editing of the organ-source pigs and refinement of immunosuppressive regimens. Major steps were the identification and deletion of expression of the three known glycan xenoantigens on pig vascular endothelial cells, the transgenic expression of human “protective” proteins, e.g., complement-regulatory, coagulation-regulatory, and anti-inflammatory proteins, and the administration of an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway. Efforts to address systemic inflammation followed. The synergy between gene editing and judicious immunomodulation appears to largely prevent graft rejection and is associated with a relatively good safety profile. Though there remains an incidence of severe or persistent proteinuria (nephrotic syndrome) in a minority of cases. This progress offers renewed hope for patients in need of life-saving organ transplants.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1432-2277
Relation: https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13942/full; https://doaj.org/toc/1432-2277
DOI: 10.3389/ti.2024.13942
Access URL: https://doaj.org/article/7dc129fa97c842d78e266bc56217cf34
Accession Number: edsdoj.7dc129fa97c842d78e266bc56217cf34
Database: Directory of Open Access Journals
More Details
ISSN:14322277
DOI:10.3389/ti.2024.13942
Published in:Transplant International
Language:English