Sinusoidal endothelial cell repopulation following ischemia/reperfusion injury in rat liver transplantation

Abstract

We evaluated the kinetics by which rat liver sinusoidal endothelial cells (LSECs) are repopulated in the reperfused transplanted liver after 18 hours of cold ischemic storage. We found that the majority of LSECs in livers cold-stored for 18 hours in University of Wisconsin solution are seriously compromised and often are retracted before transplantation. Sinusoids rapidly re-endothelialize within 48 hours of transplantation, and repopulation is coincident with up-regulation of hepatocyte vascular endothelial growth factor expression and vascular endothelial growth factor receptor-2 expression on large vessel endothelial cells and repopulating LSECs. Although re-endothelialization occurs rapidly, we show here, using several high-resolution imaging techniques and 2 different rat liver transplantation models, that engraftment of bone marrow-derived cells into functioning LSECs is routinely between 1% and 5%. Bone marrow plays a measurable but surprisingly limited role in the rapid repopulation and functional engraftment of bone marrow-derived LSECs after cold ischemia and warm reperfusion.