Development of machine perfusion strategies for liver support and beyond

Liver transplantation is a well-established treatment for end-stage liver disease, but the shortage of donor organs and the risk of ischemia-reperfusion injury remain significant challenges. Machine perfusion, an emerging technology, offers a promising solution by dynamically preserving and even repairing donor livers through extracorporeal perfusion. Recent advances in understanding the molecular mechanisms of ischemia-reperfusion injury have further highlighted the potential of machine perfusion to enhance liver preservation and expand the pool of viable donor organs.

This review aims to comprehensively summarize the research progress on machine perfusion strategies for liver preservation and explore their potential therapeutic applications beyond transplantation. We focus on the classification of machine perfusion methods based on temperature, their integration with novel therapeutic strategies, and their implications for improving liver viability and function. Key Scientific Concepts of Review: The review delves into three main types of machine perfusion: hypothermic machine perfusion (HMP), subnormothermic machine perfusion (SNMP), and normothermic machine perfusion (NMP). Each method offers distinct advantages in preserving liver function and reducing injury. We discuss how machine perfusion can be combined with mesenchymal stem cells, gene regulation, defatting cocktails, and modulators of autophagy and apoptosis to enhance liver repair and regeneration. Additionally, we highlight the potential of machine perfusion in supportive liver treatment, liver cancer therapy, and treatment efficacy evaluation. Despite these advancements, challenges such as optimizing perfusion parameters, understanding the immune status during perfusion, and ensuring long-term functionality of treated livers remain. This review emphasizes the need for further research to address these challenges and facilitate the clinical translation of machine perfusion technologies for advanced liver therapies.