Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jan 18, 2020; 10(1): 1-14
Published online Jan 18, 2020. doi: 10.5500/wjt.v10.i1.1
Therapeutics administered during ex vivo liver machine perfusion: An overview
Julianna E Buchwald, Jing Xu, Adel Bozorgzadeh, Paulo N Martins
Julianna E Buchwald, Jing Xu, Adel Bozorgzadeh, Paulo N Martins, Division of Transplantation, Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01655, United States
Author contributions: Buchwald JE, Xu J and Martins PN drafted the manuscript; Bozorgzadeh A reviewed the manuscript; all authors contributed to editing and approved the final manuscript version.
Conflict-of-interest statement: The authors have no conflict of interests to disclose.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Paulo N Martins, MD, PhD, Assistant Professor, Attending Doctor, Surgeon, Department of Surgery, Transplant Division, University of Massachusetts Medical School, 55 North Lake Avenue, Worcester, MA 01655, United States. paulo.martins@umassmemorial.org
Received: September 8, 2019
Peer-review started: September 8, 2019
First decision: October 14, 2019
Revised: October 26, 2019
Accepted: December 6, 2019
Article in press: December 6, 2019
Published online: January 18, 2020
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: Therapeutics, Liver transplantation, Ex vivo machine perfusion, Ischemia reperfusion injury, Organ preservation, Extended criteria donors

Core tip: The use of extended criteria donors has increased the donor pool of available livers for transplant but has also introduced other hurdles in protecting these vulnerable organs against ischemia-reperfusion injury (IRI). Current basic science research is aimed at mitigating the effects of IRI during the transplantation process by administering therapeutics during ex vivo liver machine perfusion. Of interest include therapeutics aimed at invoking the RNA interference pathway, utilizing defatting cocktails, and administering classes of agents such as vasodilators and anti-inflammatory drugs to reduce the damage of IRI following liver procurement and transplantation for ultimate preservation of the organ.