Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs
Abstract Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies....
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| Format: | Article |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47679-6 |
| _version_ | 1797199371907891200 |
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| author | Daniel Eisenson Yu Hisadome Michelle Santillan Hayato Iwase WeiLi Chen Akira Shimizu Alex Schulick Du Gu Armaan Akbar Alice Zhou Kristy Koenig Kasinath Kuravi Farzana Rahman Lori Sorrells Lars Burdorf Kristina DeSmet Daniel Warren Leigh Peterson Marc Lorber David Ayares Andrew Cameron Kazuhiko Yamada |
| author_facet | Daniel Eisenson Yu Hisadome Michelle Santillan Hayato Iwase WeiLi Chen Akira Shimizu Alex Schulick Du Gu Armaan Akbar Alice Zhou Kristy Koenig Kasinath Kuravi Farzana Rahman Lori Sorrells Lars Burdorf Kristina DeSmet Daniel Warren Leigh Peterson Marc Lorber David Ayares Andrew Cameron Kazuhiko Yamada |
| author_sort | Daniel Eisenson |
| collection | DOAJ |
| description | Abstract Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials. |
| first_indexed | 2024-04-24T07:14:42Z |
| format | Article |
| id | doaj.art-fb29612df711444fae0734b22e8d1904 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T07:14:42Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-fb29612df711444fae0734b22e8d19042024-04-21T11:24:10ZengNature PortfolioNature Communications2041-17232024-04-011511710.1038/s41467-024-47679-6Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigsDaniel Eisenson0Yu Hisadome1Michelle Santillan2Hayato Iwase3WeiLi Chen4Akira Shimizu5Alex Schulick6Du Gu7Armaan Akbar8Alice Zhou9Kristy Koenig10Kasinath Kuravi11Farzana Rahman12Lori Sorrells13Lars Burdorf14Kristina DeSmet15Daniel Warren16Leigh Peterson17Marc Lorber18David Ayares19Andrew Cameron20Kazuhiko Yamada21Department of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Pathology, Nippon Medical SchoolDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineUnited Therapeutics CorporationUnited Therapeutics CorporationUnited Therapeutics CorporationUnited Therapeutics CorporationUnited Therapeutics CorporationDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineUnited Therapeutics CorporationUnited Therapeutics CorporationUnited Therapeutics CorporationDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineDepartment of Surgery, Division of Transplantation, The Johns Hopkins School of MedicineAbstract Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.https://doi.org/10.1038/s41467-024-47679-6 |
| spellingShingle | Daniel Eisenson Yu Hisadome Michelle Santillan Hayato Iwase WeiLi Chen Akira Shimizu Alex Schulick Du Gu Armaan Akbar Alice Zhou Kristy Koenig Kasinath Kuravi Farzana Rahman Lori Sorrells Lars Burdorf Kristina DeSmet Daniel Warren Leigh Peterson Marc Lorber David Ayares Andrew Cameron Kazuhiko Yamada Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs Nature Communications |
| title | Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs |
| title_full | Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs |
| title_fullStr | Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs |
| title_full_unstemmed | Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs |
| title_short | Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs |
| title_sort | consistent survival in consecutive cases of life supporting porcine kidney xenotransplantation using 10ge source pigs |
| url | https://doi.org/10.1038/s41467-024-47679-6 |
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