RECONDITIONING OF TRANSPLANT LIVERS USING NORMOTHERMIC MACHINE PERFUSION AND PARACRINE FACTORS OF HUMAN LIVER STEM CELLS

The success of liver transplantation as a curative treatment for irreversible liver failure has led to a dramatic shortage in suitable donor organs. To expand the donor pool, livers previously considered unsuitable for transplantation are now increasingly used. Such ‘high-risk’ grafts are more susceptible to ischemia reperfusion injury (IRI), that results from consecutive interruption and reinstitution of blood and oxygen during the procedure. Cold static storage has been the gold standard for liver graft preservation, but recently, normothermic machine perfusion (NMP) has gained ground because of superior protective effects. We aim to investigate if NMP preservation combined with paracrine factors of human liver stem cells (HLSC) allows for a stronger reduction of the IRI of suboptimal organs, thus ‘reconditioning’ such grafts for transplantation. HLSC are a type of pluripotent adult stem cell that exert hepatoprotective and hepatoregenerative efffects through the release of extracellular vesicles. We will use preclinical models of pig isolated liver perfusion (ILP) and transplantation, and determine if NMP supplemented with HLSC-derived extracellular vesicles benefits the function of the damaged liver, regeneration and inflammation (in ILP setting), and graft survival (in vivo after transplantation). Such may be a very promising approach to improve the successful transplantation of high-risk livers.