Fas-sirna pre-transplant liver graft therapy alleviates ischemia-reperfusion injury : Preliminary results in a rodent liver transplant model
Year: 2019
Type: conference-paper
Abstract: Background: Severe ischemia reperfusion injury (IRI) limits the use of extended criteria donors (ECD) in liver transplantation (LT). Apoptosis has been shown to play an important role in IRI.\nAim: We sought to investigate if siRNA silencing of an apoptosis associated gene (FAS) could alleviate liver IRI.\nMethods: In an arterialized rat liver transplant model, a single dose of 500μg of FAS siRNA was administered in the donor 2h before organ procurement. A prolonged static cold storage time of 22h was used to intensify the IRI effects. Additional transplants were performed with an ex-vivo siRNA treatment during the liver graft perfusion in a hypothermic machime perfusion system.\nResults: Recipients of treated donors presented lower levels of AST (1067±382 x 2087±203IU/L p=0.03) and ALT (775±161 x 1777±542IU/L p=0.05) at 24h post-LT when\ncompared with the control group (Figure 1). Confocal microscopy confirmed siRNA uptake in liver grafts (Figure 2 right panel). Because donor treatment in clinical trial setting can raise potential ethical and logistical issues regarding the use of different organs by different transplant teams, we set up a model where FAS siRNA was administered to the liver during 4 hours in an ex-vivo hypothermic machine perfusion system. Here again, siRNA was uptaken by the liver and the recipients of treated grafts showed lower levels of ALT/AST at 24h post-LT.\nConclusions: Our preliminary results suggest that silencing of apoptosis-associated genes could be used to alleviate IRI post-LT, which has the potential to increase the pool of transplantable liver grafts.
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2996715318