Genetically engineered pig heart transplantation in non-human primates
Abstract Background Improvement in gene modifications of donor pigs has led to the prevention of early cardiac xenograft rejection and significantly prolonged cardiac xenograft survival in both heterotopic and orthotopic preclinical non-human primate (NHP) models. This progress formed the basis for...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00731-y |
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| author | Avneesh K. Singh Corbin E. Goerlich Tianshu Zhang Billeta Lewis Alena Hershfeld Gheorghe Braileanu Kasinath Kurvi Kathryn Rice Faith Sentz Sarah Mudd Patrick Odonkor Erik Strauss Brittney Williams Allen Burke Anuj Gupta Cinthia B. Drachenberg David Ayares Bartley P. Griffith Muhammad M. Mohiuddin |
| author_facet | Avneesh K. Singh Corbin E. Goerlich Tianshu Zhang Billeta Lewis Alena Hershfeld Gheorghe Braileanu Kasinath Kurvi Kathryn Rice Faith Sentz Sarah Mudd Patrick Odonkor Erik Strauss Brittney Williams Allen Burke Anuj Gupta Cinthia B. Drachenberg David Ayares Bartley P. Griffith Muhammad M. Mohiuddin |
| author_sort | Avneesh K. Singh |
| collection | DOAJ |
| description | Abstract Background Improvement in gene modifications of donor pigs has led to the prevention of early cardiac xenograft rejection and significantly prolonged cardiac xenograft survival in both heterotopic and orthotopic preclinical non-human primate (NHP) models. This progress formed the basis for FDA approval for compassionate use transplants in two patients. Methods Based on our earlier report of 9-month survival of seven gene-edited (7-GE) hearts transplanted (life-supporting orthotopic) in baboons, we transplanted 10 gene-edited pig hearts into baboons (n = 4) using non-ischemic continuous perfusion preservation (NICP) and immunosuppression regimen based on co-stimulation blockade by anti-CD40 monoclonal antibody. This pivotal study expands on the 7-GE backbone, with 3 additional gene edits, using 10-GE pigs as donors to baboon recipients. Results 10 GE cardiac xenografts provide life-supporting function up to 225 days (mean 128 ± 36 days) in a non-human primate model. Undetectable or latent porcine cytomegalovirus (PCMV) does not influence cardiac xenograft survival in this study but still needs more exploration with a larger cohort. Xenograft histology demonstrates adipose (Fat) deposition (n = 1), chronic vasculopathy (n = 1), micro and macro thrombosis, and acute cellular rejection (n = 1). Conclusions These data demonstrate that 10 GE cardiac xenografts have variable cardiac xenograft survival in NHP due to perhaps presence of 4th antigen and require further study. However, these 10GE organs may be suitable for clinical cardiac xenotransplantation and have already been utilized in two human cases. |
| format | Article |
| id | doaj-art-48c41c7887df49e293026b6a0ddef197 |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-48c41c7887df49e293026b6a0ddef1972025-01-12T12:37:19ZengNature PortfolioCommunications Medicine2730-664X2025-01-015111210.1038/s43856-025-00731-yGenetically engineered pig heart transplantation in non-human primatesAvneesh K. Singh0Corbin E. Goerlich1Tianshu Zhang2Billeta Lewis3Alena Hershfeld4Gheorghe Braileanu5Kasinath Kurvi6Kathryn Rice7Faith Sentz8Sarah Mudd9Patrick Odonkor10Erik Strauss11Brittney Williams12Allen Burke13Anuj Gupta14Cinthia B. Drachenberg15David Ayares16Bartley P. Griffith17Muhammad M. Mohiuddin18Department of Surgery, The University of Maryland School of MedicineDepartment of Surgery, The University of Maryland School of MedicineDepartment of Surgery, The University of Maryland School of MedicineDepartment of Surgery, The University of Maryland School of MedicineDepartment of Surgery, The University of Maryland School of MedicineDepartment of Surgery, The University of Maryland School of MedicineRevivicor IncDepartment of Pathology, The University of Maryland School of MedicineDepartment of Surgery, The University of Maryland School of MedicineDepartment of Surgery, The University of Maryland School of MedicineDepartment of Anesthesiology, The University of Maryland School of MedicineDepartment of Anesthesiology, The University of Maryland School of MedicineDepartment of Anesthesiology, The University of Maryland School of MedicineDepartment of Pathology, The University of Maryland School of MedicineDepartment of Medicine, Division of Cardiology, University of Maryland School of MedicineDepartment of Pathology, The University of Maryland School of MedicineRevivicor IncDepartment of Surgery, The University of Maryland School of MedicineDepartment of Surgery, The University of Maryland School of MedicineAbstract Background Improvement in gene modifications of donor pigs has led to the prevention of early cardiac xenograft rejection and significantly prolonged cardiac xenograft survival in both heterotopic and orthotopic preclinical non-human primate (NHP) models. This progress formed the basis for FDA approval for compassionate use transplants in two patients. Methods Based on our earlier report of 9-month survival of seven gene-edited (7-GE) hearts transplanted (life-supporting orthotopic) in baboons, we transplanted 10 gene-edited pig hearts into baboons (n = 4) using non-ischemic continuous perfusion preservation (NICP) and immunosuppression regimen based on co-stimulation blockade by anti-CD40 monoclonal antibody. This pivotal study expands on the 7-GE backbone, with 3 additional gene edits, using 10-GE pigs as donors to baboon recipients. Results 10 GE cardiac xenografts provide life-supporting function up to 225 days (mean 128 ± 36 days) in a non-human primate model. Undetectable or latent porcine cytomegalovirus (PCMV) does not influence cardiac xenograft survival in this study but still needs more exploration with a larger cohort. Xenograft histology demonstrates adipose (Fat) deposition (n = 1), chronic vasculopathy (n = 1), micro and macro thrombosis, and acute cellular rejection (n = 1). Conclusions These data demonstrate that 10 GE cardiac xenografts have variable cardiac xenograft survival in NHP due to perhaps presence of 4th antigen and require further study. However, these 10GE organs may be suitable for clinical cardiac xenotransplantation and have already been utilized in two human cases.https://doi.org/10.1038/s43856-025-00731-y |
| spellingShingle | Avneesh K. Singh Corbin E. Goerlich Tianshu Zhang Billeta Lewis Alena Hershfeld Gheorghe Braileanu Kasinath Kurvi Kathryn Rice Faith Sentz Sarah Mudd Patrick Odonkor Erik Strauss Brittney Williams Allen Burke Anuj Gupta Cinthia B. Drachenberg David Ayares Bartley P. Griffith Muhammad M. Mohiuddin Genetically engineered pig heart transplantation in non-human primates Communications Medicine |
| title | Genetically engineered pig heart transplantation in non-human primates |
| title_full | Genetically engineered pig heart transplantation in non-human primates |
| title_fullStr | Genetically engineered pig heart transplantation in non-human primates |
| title_full_unstemmed | Genetically engineered pig heart transplantation in non-human primates |
| title_short | Genetically engineered pig heart transplantation in non-human primates |
| title_sort | genetically engineered pig heart transplantation in non human primates |
| url | https://doi.org/10.1038/s43856-025-00731-y |
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