A novel off-liver sinusoidal progenitor cells in supporting transplantable bioliver engineering

Abstract

Liver transplantation is the only curative option for liver failure, which is currently limited by organ shortages. Although liver tissue engineering (LTE) with a strategy of decellularization/recellularization opens a new window to overcome this limitation, its challenges include the lack of specific seed cell sources and appropriate methods to support recellularization. In this preliminary study, both in vitro and in vivo experiments were performed. In vitro, we used novel off-liver progenitors of liver sinusoidal endothelial cells (LSECs) isolated from bone marrow mesenchymal stem cells (NG2/_BMMSCs) and a method to establish transplantable biolivers in an advanced decellularized liver scaffold (rDLS). This partial liver scaffolds (rDLS) shows advantages over whole liver scaffolds (nDLS) and also maintains both microvascular network and naturally regenerative microenvironmental niche, enhancing effective recellularization of the NG2/BMMSCs compared to nDLS in reconstructing hepatic main architectures of endothelial, sinusoidal and biliary tree before seeding hepatic stem cells (MLpvNG2 and ratOv cells). The recellularized hepatic stem cells-mediated bioliver was subsequently induced in a 3D bioreactor-like system with three different conditioned media (CM1–CM3) for different culture durations. Importantly, the NG2/_BMMSC-lined rDLSs effectively supported the functional bioliver engineering. In vivo, compared with control recipient pigs that underwent ∼90 % hepatectomy only, the recipients subjected to the same hepatectomy and received the bioliver presented greater survival durations. Overall, this study presents a new technology for fabricating a NG2/_BMMSC-based transplantable bioliver that may become a promising treatment for liver failure.