Aims: Late-outgrowth endothelial cells (OECs) exist in blood and other organs. We aimed to explore whether and how OECs participate in re-endothelialization and prevent vascular neointima formation after injury.
Methods and results: Rabbit bone marrow OECs were cultured for 4 weeks to increase their numbers. Transfusion of autologous OECs (2 × 10⁶-1 × 10⁷/kg) soon after rabbit ear central artery injury reduced the increase in intima area and the decrease in lumen area observed at days 14 and 28. Transfusion of autologous OECs (1 × 10⁷/kg) ameliorated some early (days 2 and 7) inflammatory and angiogenic responses (local and systemic) to the injury. Red fluorescence was seen within 7 days after transfusion of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein (Dil-acLDL)-incorporated OECs, and 1 h after perfusion of the isolated rabbit ear with Ringer-Locke solution containing Dil-acLDL-incorporated OECs, in the injured rabbit ear central artery. After transfusion of 5-bromo-2'-deoxyuridine (BrdU) incorporated autologous OECs, BrdU-positive cells appeared in the injured artery intima at day 3 and were present in the rescued artery endothelium at day 28. The OECs, ranging from 5%-15% of vascular smooth muscle cells (VSMCs), and the OEC-conditioned medium (5-15%) both inhibited VSMC proliferation and migration in vitro and regulated the arrangement of VSMCs. The VSMCs were helpful for OECs to form tubes in vitro.
Conclusion: Circulating OECs participate in re-endothelialization directly and inhibit VSMC migration and proliferation by a paracrine pathway; transfusion of large numbers of autologous OECs soon after vascular injury may prevent neointima formation.