Korean J Transplant.  2022 Nov;36(Supple 1):S240. 10.4285/ATW2022.F-3790.

Auxiliary liver xenotransplantation technique in a transgenic pig to non-human primate model: a surgical approach to prolong survival and better understand graft rejection

• Lee KW
• Park JB

• KMID: 2535457
• DOI: http://doi.org/10.4285/ATW2022.F-3790

Abstract

Background
Xenotransplantation using pigs' liver has long been proposed as an alternative method to overcome worldwide donor shortage, 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 a left auxiliary technique using left lateral lobe graft can potentially be a useful model to help broaden knowledge on liver xenotransplantation (XLT).
Methods
Fifteen consecutive XLTs were 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-20-0108-S1A3). Right auxiliary XLTs were performed in two cases, orthotopic XLTs in eight cases, and left aux-iliary XLTs in five cases.
Results
None of the right auxiliary XLT cases survived after surgery due to massive bleeding during the recipient right hepatectomy. Right lobe of the primate's liver encircles the inferior vena cava (IVC) and dissection between the right liver and IVC was the main cause of bleeding. Orthotopic XLT cases survived less than 7 days, and the early mortality was related to pro-found thrombocytopenia and coagulopathy. Two recipients out of the five left auxiliary XLTs survived more than 3 weeks with-out thrombocytopenia or anemia. One of them survived 34 days, which is the longest survival reported after a pig-to-primate XLT.
Conclusions
Left auxiliary XLT is a feasible operative technique for XLT experiment using non-human primates. With this approach, the feared risk of thrombocytopenia and coagulopathy associated with XLT can be minimized, thus achieving extended survival and allowing for longer evaluation of xenograft. This may help better understand histopathological and immunological changes that occur in the xenograft following XLT.