Therapeutics administered during ex vivo liver machine perfusion: An overview
Open Access
- 18 January 2020
- journal article
- review article
- Published by Baishideng Publishing Group Inc. in World Journal of Transplantation
- Vol. 10 (1), 1-14
- https://doi.org/10.5500/wjt.v10.i1.1
Abstract
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.Keywords
This publication has 85 references indexed in Scilit:
- A new liver graft preparation method for uncontrolled non-heart-beating donors, combining short oxygenated warm perfusion and prostaglandin E1Journal of Surgical Research, 2013
- The Impact of Hepatic Steatosis on Hepatic Ischemia-Reperfusion Injury in Experimental Studies: A Systematic ReviewBioMed Research International, 2013
- Liver Defatting: An Alternative Approach to Enable Steatotic Liver TransplantationAmerican Journal of Transplantation, 2012
- Ischemia–reperfusion injury in rat steatotic liver is dependent on NFκB P65 activationTransplant Immunology, 2012
- Carbon monoxide induces hypothermia tolerance in Kupffer cells and attenuates liver ischemia/reperfusion injury in ratsLiver Transplantation, 2011
- Metabolic preconditioning of donor organs: Defatting fatty livers by normothermic perfusion ex vivoMetabolic Engineering, 2009
- Origins and Mechanisms of miRNAs and siRNAsCell, 2009
- Inhibition of Kupffer cell-mediated early proinflammatory response with carbon monoxide in transplant-induced hepatic ischemia/reperfusion injury in ratsHepatology, 2008
- Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered miceJCI Insight, 2008
- A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunityThe Journal of Experimental Medicine, 2007