Study demonstrates 24-hour rat liver viability in a normothermic machine perfusion system

Reviewed by Emily Henderson, B.Sc.Nov 18 2020

In a paper published in TECHNOLOGY, a team of researchers from Massachusetts General Hospital (MGH) has demonstrated 24-hour rat liver viability in a normothermic machine perfusion (NMP) system.

Rat liver perfusion is an efficient and cost-effective method to study how various pharmacologic agents impact liver parenchyma.

Normothermic machine perfusion (NMP) has the challenge of mirroring in-vivo settings as closely as possible for the liver allograft. This allows drugs, enzymatic reactions, repair processes, and metabolic pathways to affect liver function to their full capacity.

However, under normothermic conditions (35-38°C), the perfusions become exponentially more complex when the perfusion duration is extended, severely limiting our ability to observe liver physiology and pharmacologic effects after 6 hours.

This work builds on existing NMP systems with critical modifications in technique and design to extend the perfusion time of a rat liver allograft without complications or ischemic events.

Addressing these issues in NMP greatly expands the armamentarium of experiments that can be conducted to assess how livers respond to physiologic insults and pharmacologic agents over time ex-vivo.

Another major achievement of this research is the identification of perfusion metrics that are predictive of long-term (24-hour) perfusion success. Liver oxygen consumption and rises in intra-hepatic resistance (see image) are shown to be early predictive markers of perfusion system contamination.

These markers can be utilized in future experiments to assess the stability of long NMP experiments which can save valuable time and resources in pharmacologic studies.

The team from MGH is working now to utilize long-term rat liver normothermic perfusions to trial different pharmacologic delivery mechanisms, such as lipid nanoparticles, as a novel method of targeted drug delivery.