Background: Towards the goal of utilizing more livers for transplantation, transplant centers are looking to increase the use of organs from marginal donors. Livers from these donors, have been shown to be more susceptible to preservation and reperfusion injury. CD47 regulates NO signaling. At the time of reperfusion, a paradoxical up-regulation of its ligand thrombospondin-1 has been found to inhibit CD47 signaling, leading to decrease NO signaling and tissue perfusion.

Methods: Using a porcine model of donation after cardiac death (DCD), we studied the use of antibody-mediated CD47 blockade to improve liver graft function undergoing normothermic machine perfusion. Livers from 20 pigs (5 per group) were brought under either 30 or 60 minutes of warm ischemia time (WIT) followed by the administration of treatment (antiCD47) or control (IgG) and 6 hours of normothermic liver perfusion (NELP).

Results: ALT, AST, and bile production were determined at the end of NELP (6 hours) to assess liver function in all groups (A). The 60WIT control group had the highest ALT and AST levels after 6 hours of NELP compared to the rest of groups (p=0.0014 and p=0.0220, respectively). Bile production at the end of NELP was significantly higher in both treatment groups compared to their controls (p=0.0079 for 30WIT and p=0.0308 for 60WIT). The expression of Caspase-3 after 6 hours of NELP was studied by immunofluorescence staining in 60WIT livers as a marker of reperfusion injury (B). The control group showed higher expression of Caspase-3 after 6 hours of NELP (p=0.0428). pERK levels were analyzed by Western Blot in 60WIT livers as a marker of liver regeneration. Significantly higher expression of pERK was found at the end of NELP in the treatment group compared to control livers (p=0.003).

Conclusion: In the setting of normothermic preservation, CD47 blockade can improve liver graft function by reducing both mechanisms of preservation and reperfusion injury.

CITATION INFORMATION: Garcia-Aroz S., Xu M., Wang X., Hollingshead J., Khan A., Banan B., Kang L., Zhang Z., Upadhya G., Lin Y., Manning P., Chapman W. Improving DCD Livers Graft Function Using CD47 Blockade in the Setting of Normothermic Liver Perfusion Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress