(318d) Re-Engineering of a Liver Graft Using Decellularized Liver Matrix

Orthotopic liver transplantation is the only available treatment for severe liver failure, but is currently limited by critical organ shortage. One technical challenge that has thus far limited the development of a tissue engineered liver graft is oxygen and nutrient transport. In this work, we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. Perfusion decellularization of cadaveric livers with sodium dodecyl sulfate generates a whole organ scaffold that preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes, and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function at approximately 30% functional capacity of normal liver, including albumin secretion, urea synthesis, and cytochrome P450 expression up to 10 days in vitro. Recellularized liver grafts can be endothelialized to create structures that resemble hepatic sinusoids. Recellularized liver grafts can be transplanted in rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof-of-principle for the generation of a transplantable liver graft as a potential treatment for liver disease.