Therapeutics administered during ex vivo liver machine perfusion: An overview

Although the use of extended criteria donors has increased the pool of available livers for transplant, it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury (IRI), as these "marginal" organs are particularly vulnerable to IRI during the process of procurement, preservation, surgery, and post-transplantation. In this review, we explore the current basic science research investigating therapeutics administered during ex vivo liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation process. These various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway, utilizing defatting cocktails, and administering classes of agents such as vasodilators, anti-inflammatory drugs, human liver stem cell-derived extracellular vesicles, and δ-opioid agonists in order to reduce the damage of IRI. Ex vivo machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ, effectively deliver substrates and oxygen required for cellular metabolism, therapeutically administer pharmacological or cytoprotective agents, and continuously monitor organ viability during perfusion. The use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science studies. While novel therapeutic approaches to combat IRI are being developed through basic science research, their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.