The liver has a high potential to regenerate however, the relation between oval cells and endothelial cells in the portal area during liver regeneration has not been adequately described. We have focused on sca-1+ endothelial cells (SPEC: sca-1+CD31+CD45- cells) and analyzed their localization, growth potential, and the role of these cells in damaged liver. SPECs are localized in the portal area and comprise approximately 20-30% of CD31+CD45- cells. These cells have higher growth potential than sca-1- endothelial cells and grow aggressively when the liver is severely damaged on the lateral side of the oval cells. In an in vivo study we show that when the liver is severely damaged in the presence of a VEGF (vascular endothelial growth factor)-inhibitor, the frequency of SPECs decreased and the recovery of liver volume was also delayed. These results strongly suggest that SPECs play important roles in the recovery of severely damaged liver. (C) 2007 Published by Elsevier Inc.