Background and aims: Orthotopic liver transplantation is only effective treatment for end-stage liver disease, however it is limited by shortage of donor livers. Therefore, novel methodology is required to replace organ transplantation by regenerative approaches. Tissue decellularization is an attractive technique to produce organ scaffold which can carrier any type of cell source including iPS derived cells. Decellularized scaffold was generated by removing viable cells from organ, potentially retaining liver architecture and native vascular network. To demonstrate clinical feasibility of this technology, we applied the same method to large animal and evaluated biological alterations of the scaffold after implantation. Methods: The decellularized scaffold of porcine liver was generated by whole-organ perfusion using Trypsin, SDS, TrytonX-100 and CHAPS. In order to prevent coagulation after blood perfusion, we infused the endothelial cells and hepatocytes into the scaffold under the monitoring of intravascular pressure and perfusion flow rate. In addition, we also infused the amphipathic polymer which was expected to show anti-coagulation activity in the scaffold after the reperfusion of the graft. After the implantation of the fabricated liver graft, blood flow was evaluated by angiography. We histologically evaluated cell infiltration, degree of coagulation and adhesion around the scaffold as well as cell viability and maturation of the liver architecture. Results: We could successfully transplant the recellularized scaffold in the porcine body by vessel anastomosis of portal vein and IVC. The graft was well perfused and preserved in the porcine abdominal cavity without bleeding or absorption. Histological study showed that the endothelial cells could cover most of the vessel lumen of the scaffold and the hepatocytes were well distributed in the parenchymal space. Although the coagulation was not completely avoided of the vascular system in the graft, the coagulation was less in the area sufficiently covered with the endothelial cells and the hepatocytes. Conclusions: Although it requires more improvement and customization especially for anti-coagulation, we could scale-up and optimize the system to apply this unique technology for clinical application.

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