Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix

Abstract

A critical donor organ shortage currently limits the treatment of patients with severe liver failure. Building on earlier work with decellularized hearts, Basak Uygun et al. have developed a transplantable liver graft using a decellularized liver matrix. This approach preserves the structural and functional characteristics of the native microvascular network, supports efficient recellularization and, when transplanted into rats, allows the viability and metabolic function of hepatocytes to be maintained. Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process 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 including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into 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.