A brief review of the current status of pig islet xenotransplantation
An estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of islets from gene-edited pigs, if successful, wo...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1366530/full |
| _version_ | 1797299764131266560 |
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| author | David K. C. Cooper Lisha Mou Lisha Mou Rita Bottino |
| author_facet | David K. C. Cooper Lisha Mou Lisha Mou Rita Bottino |
| author_sort | David K. C. Cooper |
| collection | DOAJ |
| description | An estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of islets from gene-edited pigs, if successful, would resolve this problem. Pigs are now available in which the expression of the three known xenoantigens against which humans have natural (preformed) antibodies has been deleted, and in which several human ‘protective’ genes have been introduced. The transplantation of neonatal pig islets has some advantages over that of adult pig islets. Transplantation into the portal vein of the recipient results in loss of many islets from the instant blood-mediated inflammatory reaction (IBMIR) and so the search for an alternative site continues. The adaptive immune response can be largely suppressed by an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway, whereas conventional therapy (e.g., based on tacrolimus) is less successful. We suggest that, despite the need for effective immunosuppressive therapy, the transplantation of ‘free’ islets will prove more successful than that of encapsulated islets. There are data to suggest that, in the absence of rejection, the function of pig islets, though less efficient than human islets, will be sufficient to maintain normoglycemia in diabetic recipients. Pig islets transplanted into immunosuppressed nonhuman primates have maintained normoglycemia for periods extending more than two years, illustrating the potential of this novel form of therapy. |
| first_indexed | 2024-03-07T22:56:21Z |
| format | Article |
| id | doaj.art-84c69ac459bb42eeb785198b33e29052 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T22:56:21Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-84c69ac459bb42eeb785198b33e290522024-02-23T04:27:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13665301366530A brief review of the current status of pig islet xenotransplantationDavid K. C. Cooper0Lisha Mou1Lisha Mou2Rita Bottino3Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United StatesInstitute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, ChinaMetaLife Center, Shenzhen Institute of Translational Medicine, Shenzhen, Guangdong, ChinaImagine Islet Center, Imagine Pharma, Pittsburgh, PA, United StatesAn estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of islets from gene-edited pigs, if successful, would resolve this problem. Pigs are now available in which the expression of the three known xenoantigens against which humans have natural (preformed) antibodies has been deleted, and in which several human ‘protective’ genes have been introduced. The transplantation of neonatal pig islets has some advantages over that of adult pig islets. Transplantation into the portal vein of the recipient results in loss of many islets from the instant blood-mediated inflammatory reaction (IBMIR) and so the search for an alternative site continues. The adaptive immune response can be largely suppressed by an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway, whereas conventional therapy (e.g., based on tacrolimus) is less successful. We suggest that, despite the need for effective immunosuppressive therapy, the transplantation of ‘free’ islets will prove more successful than that of encapsulated islets. There are data to suggest that, in the absence of rejection, the function of pig islets, though less efficient than human islets, will be sufficient to maintain normoglycemia in diabetic recipients. Pig islets transplanted into immunosuppressed nonhuman primates have maintained normoglycemia for periods extending more than two years, illustrating the potential of this novel form of therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1366530/fulldiabetesisletspancreaticnonhuman primatespiggenetically-engineered |
| spellingShingle | David K. C. Cooper Lisha Mou Lisha Mou Rita Bottino A brief review of the current status of pig islet xenotransplantation Frontiers in Immunology diabetes islets pancreatic nonhuman primates pig genetically-engineered |
| title | A brief review of the current status of pig islet xenotransplantation |
| title_full | A brief review of the current status of pig islet xenotransplantation |
| title_fullStr | A brief review of the current status of pig islet xenotransplantation |
| title_full_unstemmed | A brief review of the current status of pig islet xenotransplantation |
| title_short | A brief review of the current status of pig islet xenotransplantation |
| title_sort | brief review of the current status of pig islet xenotransplantation |
| topic | diabetes islets pancreatic nonhuman primates pig genetically-engineered |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1366530/full |
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