Commentary proposes treating donor organs during machine perfusion before transplantation

Commentary proposes treating donor organs during machine perfusion before transplantation

On September 14, a scientific commentary proposed using the time a retrieved organ spends connected to a perfusion machine to administer drug treatment. The commentary was prompted by a study in Cell on FXT-001, an experimental compound that protects cell membranes from oxidative damage.

Machine perfusion pumps oxygenated fluid or blood through a retrieved organ. This sustains the organ outside the body and allows its function to be assessed before transplantation. The commentary proposes using this same period to deliver a drug directly to the organ and measure its effect through indicators of organ function.

Damage begins when the organ loses its supply of oxygen and nutrients, and oxidative reactions intensify when blood flow is restored. Iron accelerates the oxidation of lipids in cell membranes. Membrane damage can lead to ferroptosis, a regulated form of cell death.

In 116 liver transplant recipients, malondialdehyde, a marker of lipid oxidation, peaked 30 minutes after blood flow was restored. Its level was associated with AST, a laboratory marker of liver injury. FXT-001 binds iron and inhibits free radical chain reactions in membrane lipids, which was the basis for testing it against this mechanism of injury.

In pig livers, FXT-001 was added to the cold storage solution; during subsequent perfusion, less AST was released into the perfusion fluid. In experiments with pig lungs, the compound was added to the perfusion fluid at the start of perfusion, and less water accumulated in the lungs.

Five pairs of human lungs deemed unsuitable for transplantation underwent simultaneous perfusion: one lung in each pair received FXT-001, and the other received a control solution. This paired comparison reduces the influence of differences between donors. Treated lungs accumulated less excess water, gained less weight, and retained their ability to expand more effectively.

The commentary proposes administering a drug locally during perfusion and assessing organ function before transplantation.