Jong-Min Kim1,2,3,4, So-Hee Hong1,2,3,5, Hyunwoo Chung1,2,5, Jun-Seop Shin1,3,4, Byoung-Hoon Min1,3,4, Hyun Je Kim1,2,4,5,6, Jiyeon Kim2,3, Eung Soo Hwang1,2,3, Hee-Jung Kang1,7, Jongwon Ha8, Chung-Gyu Park1,2,3,4,5. 1. Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul, Korea. 2. Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Korea. 3. Institute of Endemic Diseases, College of Medicine, Seoul National University, Seoul, Korea. 4. Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea. 5. Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea. 6. Department of Dermatology, Samsung Medical Center, Seoul, Korea. 7. Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea. 8. Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Abstract
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.
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.
Authors: Wayne J Hawthorne; Evelyn J Salvaris; Yi Vee Chew; Heather Burns; Joanne Hawkes; Helen Barlow; Min Hu; Andrew M Lew; Mark B Nottle; Philip J O'Connell; Peter J Cowan Journal: Front Immunol Date: 2022-06-16 Impact factor: 8.786
Authors: Qimeng Gao; Robert Davis; Zachary Fitch; Michael Mulvihill; Brian Ezekian; Paul Schroder; Robin Schmitz; Mingqing Song; Frank Leopardi; Marianna Ribeiro; Allison Miller; Dimitrios Moris; Brian Shaw; Kannan Samy; Keith Reimann; Kyha Williams; Bradley Collins; Allan D Kirk Journal: Xenotransplantation Date: 2021-11 Impact factor: 3.907