A3: Targeting the Islet / Vascular Inflammation Interface in xenograft dysfunction

A major limitation in islet xenotransplantation is the immediate blood-mediated inflammatory reaction (IBMIR), which leads to dysfunction of a great portion of the transplanted islets. We focus here on targeting IBMIR by manipulating inflammation in the recipient. In this context, (a) we will target the vascular-endothelial inflammation and activation by focusing on the endothelial receptor Robo4 and its ligand Slit2 and (b) manipulate inflammation within the hepatic microenvironment of the recipient by modulating the balance between pro-inflammatory and anti-inflammatory / pro-resolving lipid mediators, in order to prevent IBMIR and xenograft dysfunction.