Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs

Implanted bioengineered livers have not exceeded three days of continuous perfusion. Here, we show that decellularized whole porcine livers revascularized with human umbilical endothelial cells and implanted heterotopically into immunosuppressed pigs whose spleen has been removed can sustain perfusion for up to 15 days. We identified peak glucose consumption rate as a main predictor of the patency of the revascularized bioengineered livers (rBELs). On heterotopic implantation of the rBELs into pigs in the absence of anticoagulation therapy led to sustained perfusion for 3 days, followed by significant immune responses directed against the human endothelial cells. A 10-day steroid-based immunosuppression protocol and a splenectomy at time of rBEL implantation reduced the immune responses and resulted in continuous perfusion of the rBELs for over two weeks. We also show that the human endothelial cells in the perfused rBELs colonize the liver sinusoids and express sinusoidal endothelial markers similar to those in normal liver tissue. Revascularized liver scaffolds that can maintain blood perfusion at physiological pressures might eventually help overcome the chronic shortage of transplantable human livers.