Long-term porcine islet graft survival in diabetic non-human primates treated with clinically available immunosuppressants
Jong-Min Kim
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorSo-Hee Hong
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorHyunwoo Chung
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorJun-Seop Shin
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorByoung-Hoon Min
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorHyun Je Kim
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
Department of Dermatology, Samsung Medical Center, Seoul, Korea
Search for more papers by this authorJiyeon Kim
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorEung Soo Hwang
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorHee-Jung Kang
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
Search for more papers by this authorJongwon Ha
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Chung-Gyu Park
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
Correspondence
Chung-Gyu Park, Department of Microbiology and Immunology, Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
Email: [email protected]
Search for more papers by this authorJong-Min Kim
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorSo-Hee Hong
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorHyunwoo Chung
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorJun-Seop Shin
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorByoung-Hoon Min
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorHyun Je Kim
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
Department of Dermatology, Samsung Medical Center, Seoul, Korea
Search for more papers by this authorJiyeon Kim
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorEung Soo Hwang
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorHee-Jung Kang
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
Search for more papers by this authorJongwon Ha
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Chung-Gyu Park
Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea
Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea
Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
Correspondence
Chung-Gyu Park, Department of Microbiology and Immunology, Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
Email: [email protected]
Search for more papers by this authorAbstract
Background
Although pancreatic islet transplantation is becoming an effective therapeutic option for patients with type 1 diabetes (T1D) who suffer from a substantially impaired awareness of hypoglycemia, its application is limited due to the lack of donors. Thus, pig-to-human islet xenotransplantation has been regarded as a promising alternative due to the unlimited number of “donor organs.” Long-term xenogeneic islet graft survival in pig-to-non-human primate (NHP) models has mainly been achieved by administering the anti-CD154 mAb-based immunosuppressant regimen. Since the anti-CD154 mAb treatment has been associated with unexpected fatal thromboembolic complications in clinical trials, the establishment of a new immunosuppressant regimen that is able to be directly applied in clinical trials is an urgent need.
Methods
We assessed an immunosuppressant regimen composed of clinically available agents at porcine islet transplantation in consecutive diabetic NHPs.
Results
Porcine islet graft survival in consecutive diabetic NHPs (n = 7; >222, >200, 181, 89, 62, 55, and 34 days) without severe adverse events.
Conclusion
We believe that our study could contribute greatly to the initiation of islet xenotransplantation clinical trials.
CONFLICT OF INTEREST
The authors of this manuscript have no conflicts of interest to disclose, as described by the American Journal of Transplantation.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| xen12659-sup-0001-SupInfo.docxWord document, 330.4 KB | Supplementary Material |
| xen12659-sup-0002-AppendixS1.docxWord document, 33.9 KB | Appendix S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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