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107.1 Auxiliary liver xenotransplantation technique in a transgenic pig-to-non-human primate model: A surgical approach to prolong survival

Kyo Won Lee, Korea

Association professor
Department of Surgery
Samsung Medical Center

Abstract

Auxiliary liver xenotransplantation technique in a transgenic pig-to-non-human primate model: A surgical approach to prolong survival

Kyo Won Lee1, Jae Berm Park 1, Sung Hae Park 1, Kimyung Choi2, Joohyun Shim2, Jae Seok Yang 3, Sung Joo Kim4.

1Department of Surgery , Samsung Medical Center, Seoul , Korea; 2Optipharm Inc , Cheongju-si, Korea; 3Department of internal medicine , Yonsei University College of Medicine, Seoul , Korea; 4GenNBio, Pyeongtaek-Si, Korea

Introduction: Xenotransplantation using pigs' liver has long been proposed as an alternative method to overcome this donor shortage issue or more importantly as a bridge to allotransplantation. However, xenotransplantation in a pig to primate model has been challenged by profound thrombocytopenia and coagulation disorders, leading to uncontrollable hemorrhage and early mortality. Here we suggest that the left auxiliary technique using left lateral lobe graft can potentially be a useful model to help broaden knowledge on liver xenotransplantation (XLT).
Materials and methods: Fifteen consecutive (XLT) was carried out using male cynomolgus monkeys of specific pathogen-free health status as recipients. All experiments were approved by the Institutional Animal Care and Use Committee in Seoul National University Hospital (SNUH-IACUC). Right auxiliary XLT was performed in two cases, orthotopic XLT was performed in eight cases, and left auxiliary XLT was performed in five cases.
Results: Right auxiliary XLT cases were not survived after surgery from the massive bleeding during the recipient right liver hepatectomy. Right liver of primate encircle the inferior vena cava (IVC) and dissection between the right liver and IVC was the main cause of bleeding. Orthtopic XLT cases survived less than seven days which was resulted from the profound thrombocytopenia and coagulation disorder. Among the five left auxiliary XLT cases (figure 1), two cases survived more than three weeks without profound thrombocytopenia and anemia. One of that two animals survived 34 days after XLT which was reported longest survival after XLT performed in primate.   
Conclusion: Left auxiliary XLT is suitable operational technique for XLT experiment using non-human primate. With this technique, risk of thrombocytopenia and coagulation disorder can be minimized and long term survival after XLT can be obtained which was essential to assess the graft condition such as rejection after XLT.

The funding for this research was supported by a grant from the Korean Health Technology R&D Project through the Ministry of Health and Welfare of the Republic of Korea (HI20C0056)..

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IPITA-IXA-CTRMS Joint Congress • San Diego, CA, USA • October 26-29, 2023
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