Development of a Large Animal Model of Ischemia-free Liver Transplantation in Pigs

Yunhua Tang; Jiahao Li; Tielong Wang; Zhiheng Zhang; Shanzhou Huang; Zebin Zhu; Linhe Wang; Qiang Zhao; Zhiyong Guo; Xiaoshun He

doi:10.1097/TXD.0000000000001597

Development of a Large Animal Model of Ischemia-free Liver Transplantation in Pigs

Transplant Direct. 2024 Apr 11;10(5):e1597. doi: 10.1097/TXD.0000000000001597. eCollection 2024 May.

Authors

Yunhua Tang^{1

2

3}, Jiahao Li^{1

2

3}, Tielong Wang^{1

2

3}, Zhiheng Zhang^{1

2

3}, Shanzhou Huang^{1

2

3}, Zebin Zhu^{1

2

3}, Linhe Wang^{1

2

3}, Qiang Zhao^{1

2

3}, Zhiyong Guo^{1

2

3}, Xiaoshun He^{1

2

3}

Affiliations

¹ Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
³ Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.

Abstract

Background: In organ transplantation, ischemia, and reperfusion injury (IRI) is considered as an inevitable event and the major contributor to graft failure. Ischemia-free liver transplantation (IFLT) is a novel transplant procedure that can prevent IRI and provide better transplant outcomes. However, a large animal model of IFLT has not been reported. Therefore, we develop a new, reproducible, and stable model of IFLT in pigs for investigating mechanisms of IFLT in IRI.

Methods: Ten pigs were subjected to IFLT or conventional liver transplantation (CLT). Donor livers in IFLT underwent 6-h continuous normothermic machine perfusion (NMP) throughout graft procurement, preservation, and implantation, whereas livers in CLT were subjected to 6-h cold storage before implantation. The early reperfusion injury was compared between the 2 groups.

Results: Continuous bile production, low lactate, and liver enzyme levels were observed during NMP in IFLT. All animals survived after liver transplantation. The posttransplant graft function was improved with IFLT when compared with CLT. Minimal histologic changes, fewer apoptotic hepatocytes, less sinusoidal endothelial cell injury, and proinflammatory cytokine (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) release after graft revascularization were documented in the IFLT group versus the CLT group.

Conclusions: We report that the concept of IFLT is achievable in pigs. This innovation provides a potential strategy to investigate the mechanisms of IRI and provide better transplant outcomes for clinical practice.