So-Hee Hong1,2,3,4,5, Hyun-Je Kim1,2,3, Seong-Jun Kang1,2,5, Chung-Gyu Park6,7,8,9,10,11. 1. Xenotransplantation Research Center, Seoul National University, College of Medicine, Seoul, South Korea. 2. Department of Microbiology and Immunology, Seoul National University, College of Medicine, Seoul, South Korea. 3. Institute of Endemic Diseases, Seoul National University, College of Medicine, Seoul, South Korea. 4. Cancer Research Institute, Seoul National University, College of Medicine, Seoul, South Korea. 5. Department of Biomedical Sciences, Seoul National University, College of Medicine, Seoul, South Korea. 6. Xenotransplantation Research Center, Seoul National University, College of Medicine, Seoul, South Korea. chgpark@snu.ac.kr. 7. Department of Microbiology and Immunology, Seoul National University, College of Medicine, Seoul, South Korea. chgpark@snu.ac.kr. 8. Institute of Endemic Diseases, Seoul National University, College of Medicine, Seoul, South Korea. chgpark@snu.ac.kr. 9. Cancer Research Institute, Seoul National University, College of Medicine, Seoul, South Korea. chgpark@snu.ac.kr. 10. Department of Biomedical Sciences, Seoul National University, College of Medicine, Seoul, South Korea. chgpark@snu.ac.kr. 11. Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. chgpark@snu.ac.kr.
Abstract
PURPOSE OF REVIEW: Porcine islet xenotransplantation is a promising alternative to overcome the shortage of organ donors. For the successful application of islet xenotransplantation, robust immune/inflammatory responses against porcine islets should be thoroughly controlled. Over the last few decades, there have been numerous attempts to surmount xenogeneic immune barriers. In this review, we summarize the current progress in immunomodulatory therapy for the clinical application of porcine islet xenotransplantation. RECENT FINDINGS: Long-term graft survival of porcine islets was achieved by using anti-CD154 Ab-based regimens in a preclinical non-human primate (NHP) model. However, owing to a serious complication of thromboembolism in clinical trials, the development of an anti-CD154 Ab-sparing immunosuppressant procedure is required. The efficacy of new immunosuppressive practices that employ anti-CD40 Abs or other immunosuppressive reagents has been tested in a NHP model to realize their utility in porcine islet xenotransplantation. The recent progress in the development of immunomodulatory approaches, including the immunosuppressive regimen, which enables long-term graft survival in a pig-to-non-human primate islet xenotransplantation model, with their potential clinical applicability was reviewed.
PURPOSE OF REVIEW: Porcine islet xenotransplantation is a promising alternative to overcome the shortage of organ donors. For the successful application of islet xenotransplantation, robust immune/inflammatory responses against porcine islets should be thoroughly controlled. Over the last few decades, there have been numerous attempts to surmount xenogeneic immune barriers. In this review, we summarize the current progress in immunomodulatory therapy for the clinical application of porcine islet xenotransplantation. RECENT FINDINGS: Long-term graft survival of porcine islets was achieved by using anti-CD154 Ab-based regimens in a preclinical non-human primate (NHP) model. However, owing to a serious complication of thromboembolism in clinical trials, the development of an anti-CD154 Ab-sparing immunosuppressant procedure is required. The efficacy of new immunosuppressive practices that employ anti-CD40 Abs or other immunosuppressive reagents has been tested in a NHP model to realize their utility in porcine islet xenotransplantation. The recent progress in the development of immunomodulatory approaches, including the immunosuppressive regimen, which enables long-term graft survival in a pig-to-non-human primate islet xenotransplantation model, with their potential clinical applicability was reviewed.
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