Background: Previous studies have shown that mesenchymal stem cells (MSCs) transplantation can promote neovascularization and regenerate damaged myocardium. However, it remains unknown whether MSCs seeding can be used to repair injured cellular components in vascular diseases. In this study we explored the feasibility of applying MSCs to endothelium repair in endothelial damage and vasoproliferative disorders. Methods: Exvivomodelof endotheliumrepair wasdeveloped inwhichrabbitvascular smoothmuscle cells (SMCs) wereinoculated intothe upper chamber and rabbit endothelial cells (ECs)/human MSCs into the lower chamber of a co-culture system.3H-TdR incorporation and PCNA protein expression were assayed and migrated number of SMCs was calculated to evaluate the effect of MSCs seeding on SMCs growth. Flk-1 and vWF protein expressions were observed to analyze the plasticity of the seeded MSCs along endothelial lineage. Results: Inthisco-culture system,novWFproteinbutFlk-1 proteinwasobserved inthe25.71%of MSCsafter havingbeen co-cultured with mature rabbit ECs for 5 days. Compared with the control group, the proliferation and migration of SMCs was significantly increased by proliferative ECs but decreased by confluent ECs (n=6，P<0.01). MSCs seeding decreased the proliferation and migration of SMCsb compatible with the effect of proliferative ECs (n=6, P<0.001). However, no inhibition on SMCs growth was observed with MSCs seedingb in comparison to the effect of confluent ECs. Conclusions: MSCs seeding can inhibit the proliferation and migration of SMCs. MSCs co-cultured with mature ECs have the ability to undergo milieu-dependent differentiation toward ECs. ©2005 Elsevier Ireland Ltd. All rights reserved.