Sustained In Vivo Perfusion of a Re-Endothelialized Tissue Engineered Porcine Liver

Abstract

Objective A tissue engineered liver graft will provide a sustainable source of transplantable organs. A porcine liver scaffold was utilized to develop a re-endothelialized revascularized liver capable of sustained in vivo perfusion in a large animal model. Background Liver transplantation remains the only definitive treatment for end-stage liver disease. With only 6000 donor livers available each year nationally, the need far exceeds the supply. Innovative cell-based therapies, such as hepatic tissue engineering, offer alternatives to supplement the limited supply of quality organs for transplantation. Methods Whole livers harvested from 6-10 kg pigs underwent rapid perfusion decellularization resulting in an acellular scaffold with an intact vascular network and capsule. Scaffolds were re-endothelialized with Human or Porcine Endothelial Cells derived from Human or Pig Umbilical Vein (HUVEC or PUVEC cells) at physiologic perfusion pressures. PUVEC seeded grafts were implanted as auxiliary liver transplants in recipient pigs. Results Non-endothelialized grafts demonstrated thrombosis at 30 minutes post perfusion with absent vascular inflow. Re-endothelialized grafts demonstrated patent vascular inflow, absence of gross thrombus, and patent post-explant portal venogram after 72 hours of in vivo hemoperfusion. Histologic review demonstrated viable endothelial cells following graft explant. Conclusions Vascular patency of a re-endothelialized porcine whole liver graft was achieved in vivo in the absence of systemic anticoagulation. This implantable bioengineered re-endothelialized liver offers early proof of concept of a future unlimited source of patient specific livers for transplantation.