The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation
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 challenge...
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| Format: | Article |
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Frontiers Media S.A.
2025-01-01
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| Series: | Transplant International |
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| Online Access: | https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13942/full |
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| author | S. A. Sanatkar K. Kinoshita A. Maenaka H. Hara D. K. C. Cooper |
| author_facet | S. A. Sanatkar K. Kinoshita A. Maenaka H. Hara D. K. C. Cooper |
| author_sort | S. A. Sanatkar |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7dc129fa97c842d78e266bc56217cf34 |
| institution | Kabale University |
| issn | 1432-2277 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Transplant International |
| spelling | doaj-art-7dc129fa97c842d78e266bc56217cf342025-01-13T14:28:21ZengFrontiers Media S.A.Transplant International1432-22772025-01-013710.3389/ti.2024.1394213942The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ TransplantationS. A. Sanatkar0K. Kinoshita1A. Maenaka2H. Hara3D. K. C. Cooper4Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesThe Transplantation Institute at the Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, ChinaCenter for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesAn 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.https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13942/fullimmunosuppressionxenotransplantationtransplantation immunologyswinenon-human primate |
| spellingShingle | S. A. Sanatkar K. Kinoshita A. Maenaka H. Hara D. K. C. Cooper The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation Transplant International immunosuppression xenotransplantation transplantation immunology swine non-human primate |
| title | The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation |
| title_full | The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation |
| title_fullStr | The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation |
| title_full_unstemmed | The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation |
| title_short | The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation |
| title_sort | evolution of immunosuppressive therapy in pig to nonhuman primate organ transplantation |
| topic | immunosuppression xenotransplantation transplantation immunology swine non-human primate |
| url | https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13942/full |
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