Liver Transplantation Model

Indication / Application

Preclinical efficacy validation of novel immunosuppressive drugs, evaluation of organ preservation solutions (e.g., UW solution, HTK solution) and perfusion technologies, research into the mechanisms of hepatic ischemia-reperfusion injury (IRI), and validation of interventional vascular and biliary devices.

Modeling Method

1.Rodent Orthotopic Liver Transplantation (OLT - Modified Kamada Cuff Technique):

• Donor Harvest: The donor liver is isolated, cannulated via the portal vein, and flushed with cold preservation solution. The suprahepatic vena cava, portal vein, and infrahepatic vena cava are prepared.

• Cuff Preparation: Polyethylene cuffs are precisely mounted onto the donor portal vein and infrahepatic vena cava to allow rapid, sutureless anastomosis, significantly minimizing warm ischemia time (WIT).

• Recipient Operation & Revascularization: The recipient's native liver is removed. The graft is positioned orthotopically. The suprahepatic vena cava is anastomosed using continuous microsutures, followed by rapid cuff insertion for the portal vein and infrahepatic inferior vena cava. The bile duct is reconstructed using an internal stent tube.

2.Large Animal Porcine Orthotopic Liver Transplantation:

• Utilizing Bama mini-pigs, this clinically identical procedure involves hand-sewn vascular anastomoses of the hepatic veins, portal vein, hepatic artery, and biliary system under full systemic monitoring and mechanical ventilation, providing human-scale translational data.

Clinical Relevance

• Immunological Fidelity: By pairing specific inbred rat strains (e.g., Lewis donors to Brown Norway recipients), our models perfectly mirror human acute cellular rejection, characterized by severe inflammatory infiltration, endophlebitis, and bile duct damage.

• Ischemia-Reperfusion Simulation: Replicates clinical post-transplant syndrome and early graft dysfunction, allowing developers to test therapeutics designed to salvage marginal grafts or reduce ischemia-related tissue necrosis.

• Surgical Scale for Devices & Biomaterials: Our porcine OLT platform offers a clinical-grade surgical suite, allowing sponsors to evaluate advanced vascular anastomosis devices, hemostatic patches, and ex vivo machine perfusion systems.

Key Evaluation Endpoints

1.In Vivo & Survival Monitoring

• Postoperative Survival Curves: Daily tracking of recipient survival rates and clinical health scoring.

• Intraoperative Hemodynamics: Real-time monitoring of warm ischemia time (WIT), cold ischemia time (CIT), anhepatic phase duration, and systemic blood pressure stabilization.

• Non-Invasive Ultrasound Imaging: High-resolution Doppler ultrasound to verify graft vascular patency, portal vein blood flow velocity, and biliary duct dilatation.

2.Hepatobiliary Function & Systemic Profiling

• Hepatic Injury Markers: Serial blood sampling to monitor serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Lactate Dehydrogenase (LDH) spikes as direct indicators of IRI and hepatocellular necrosis.

• Biliary Function Diagnostics: Measurement of serum Total Bilirubin (TBIL) and Alkaline Phosphatase (ALP) to assess bile duct patency and secretory function.

• Immune Activation Profiles: Serial tracking of systemic and localized levels of key cytokines (IL-2, IFN-gamma, TNF-alpha, IL-6) and donor-specific antibody (DSA) generation.

3.Histopathology & Graft Integrity (Microstructural Analysis)

• Graft Rejection Scoring (Banff Criteria): H&E staining of the grafted liver to grade acute cellular rejection based on portal inflammation, bile duct damage, and subendothelial venulitis.

• Ischemia-Reperfusion Injury Assessment: Suzuki's histological grading to score sinusoidal congestion, hepatocyte vacuolization, and focal necrosis.

• Apoptosis & Tissue Remodeling: TUNEL assays to quantify hepatocellular apoptosis, paired with IHC tracking of CD3 (T-cell infiltration) and myeloperoxidase (MPO) activity (neutrophil infiltration).