Improving Liver Graft Function Using CD47 Blockade in the Setting of Normothermic Machine Perfusion

Area of Science:

• Transplantation immunology
• Organ preservation
• Machine perfusion

Background:

• Transplant centers aim to increase liver transplantation by utilizing organs from marginal donors.
• Organs from marginal donors are more vulnerable to preservation and reperfusion injury.

Purpose of the Study:

• To investigate the efficacy of antibody-mediated CD47 blockade in improving liver graft function.
• To assess the impact of CD47 blockade on liver injury during normothermic machine perfusion in a porcine model of donation after circulatory death.

Main Methods:

• Utilized a porcine model with donation after circulatory death.
• Administered CD47 monoclonal antibody (CD47mAb) or control antibodies to livers subjected to 30 or 60 minutes of warm ischemia.
• Subjected livers to 6 hours of normothermic extracorporeal liver perfusion.

Main Results:

• CD47mAb treatment significantly reduced alanine transaminase levels and increased bile production in livers with both 30 and 60 minutes of warm ischemia.
• CD47 blockade led to decreased thrombospondin-1 protein levels and reduced caspase-3 expression.
• Enhanced expression of phosphorylated extracellular signal-regulated kinase was observed in CD47mAb-treated livers.

Conclusions:

• CD47mAb treatment mitigates ischemia/reperfusion injury by downregulating CD47/thrombospondin-1 signaling.
• This approach may reduce necrosis and apoptosis post-reperfusion.
• CD47 blockade shows potential to enhance liver regeneration during normothermic perfusion.