Establishment of liver cancer disease model via normothermic machine perfusion.

Abstract

Purpose: To date, there are no effective therapeutic strategies for hepatocellular carcinoma (HCC). Traditionally, researches on HCC were carried out using hepatocellular carcinoma cells, organoids, and animal models. However, these models cannot accurately replicate the pathophysiological conditions underlying the onset and progression of human HCC. Therefore, more effective disease models are needed to study HCC.

Methods: Ten disease livers from HCC patients who underwent transplantation were subjected to normothermic machine perfusion (NMP) via the hepatic artery and portal vein in vitro. Perfusion parameters, blood gas levels, and contrast-enhanced ultrasound (CEUS) were continuously monitored to assess alterations in tumor activity. RNA sequencing (RNA-seq) and next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) were employed to assess the preservation of hepatic tissue integrity and tumor mutational profiles during in vitro perfusion. Oxaliplatin +5-FU was used to conduct the liver cancer treatment research.

Results: Normothermic machine perfusion successfully maintained liver survival for 92 h in vitro. Contrast-enhanced ultrasound can be used to assess alterations in tumor and liver activity during normothermic machine perfusion. The sequencing analysis revealed that normothermic machine perfusion (NMP) effectively preserved hepatic tissue integrity while retaining tumor genomic stability. The normothermic machine perfusion model of HCC can be used for the study of anti-cancer therapy.

Conclusions: Contrast-enhanced ultrasound can monitor alterations in tumor and liver activity, while normothermic machine perfusion can sustain the long-term survival of the liver in vitro, thus maintaining normal tumor characteristics. Therefore, this model provides a novel approach for studying tumor therapy.