FAS-siRNA Pre-transplant liver graft therapy alleviates ischemia-reperfusion injury: Preliminary results in in a rodent liver transplant model

Bonaccorsi Riani, Eliano;Gillooly, A;Iesari, Samuele;Bruggenwirth, I;Martins, PN;et.al.
(2019) 19th Congress of the European Society for Organ Transplantation — Location: Copenhagen, Denmark (15.September.2019)

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Authors
  • Bonaccorsi Riani, ElianoUCLouvain
    Author
  • Gillooly, A
    Author
  • Iesari, Samueleorcid-logoUCLouvain
    Author
  • Bruggenwirth, I
    Author
  • Komuta, MinaUCLouvain
    Author
  • Gianello, Pierreorcid-logoUCLouvain
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  • Martins, PN
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Abstract
(en) 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. Aim: We sought to investigate if siRNA silencing of an apoptosis associated gene (FAS) could alleviate liver IRI. Methods: 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. Results: 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 compared 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. Conclusions: 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.
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Bonaccorsi Riani, E., Gillooly, A., Iesari, S., Bruggenwirth, I., Fergunson, C., Komuta, M., Leuvennik, H., Porte, R., Bozorgzadeh, A., Khvorova, A., Gianello, P., & Martins, P. (2019). FAS-siRNA Pre-transplant liver graft therapy alleviates ischemia-reperfusion injury: Preliminary results in in a rodent liver transplant model. Transplant International, 32(Supplement 2), 114-115. https://hdl.handle.net/2078.5/97107 (Original work published 2019)