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| Delivery of genetic load during ex situ liver machine perfusion with potential for CRISPR-Cas9 gene editing: An innovative strategy for graft treatment |
| Eliano Bonaccorsi-Riani a , b , c , Andrew Gillooly c , Isabel M.A. Bruggenwirth c , d , Paulo N. Martins c , ∗ |
a Abdominal Transplant Unit, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium
b Pôle de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium
c Department of Surgery, Transplant Division, University of Massachusetts, Worcester-Massachusetts, USA
d Department of Surgery, Section of hepatobiliary surgery and liver transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands |
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Abstract Over the years, the shortage of suitable donor organs has challenged the transplant community in performing life-saving liver transplantation (LT). Recent reports from European and American liver transplant registries show persistently high waitlist mortality rates ranging between 10% and 18% [1,2]. To cope with this, liver transplant surgeons are increasingly forced to transplant organs from extended criteria donors. However, it is well known that these organs are more susceptible to the consequences of ischemia-reperfusion injury (IRI), including primary non-function (PNF) and non-anastomotic biliary strictures (NAS) after transplantation, which, by consequence, can increase the number of retransplantations, making organ shortage an endless cycle [3]. This unfavorable scenario has created a fertile environment for the development of organ machine perfusion (MP) strategies aiming to assess and optimize organs before transplantation [4]. A large amount of research has resulted in the development of different perfusion devices and protocols, which have been tested in preclinical and clinical studies, and, more recently, in randomized clinical trials [5]. Currently, hypothermic oxygenated machine perfusion (HOPE) is mainly used to improve mitochondrial status by decreasing oxidative stress and increasing cellular adenosine triphosphate (ATP) levels [6,7], whereas normothermic MP is better suited for evaluation of graft quality during the perfusion session by measuring different biological and physiological parameters.
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2021, Vol. 20 
