Endothelial-like cells differentiated from mesenchymal stem cells attenuate neointimal hyperplasia after vascular injury

The present study investigated the contribution of bone marrow-derived mesenchymal stem cells (BM-MSCs) to neointimal formation, and whether endothelial-like cells (ELCs) differentiated from BM-MSCs could attenuate intimal hyperplasia following vascular injury. BM-MSCs were isolated from rat femurs and tibias and expanded ex vivo. Differentiation into ELCs was induced by cultivation in the presence of 50 ng/ml vascular endothelial growth factor (VEGF). MSCs and ELCs were labeled with BrdU and injected via the femoral vein on the day of a balloon-induced carotid artery injury. Carotid artery morphology and histology were examined using ultrasound biomicroscopy and immunohistochemistry. Flow cytometry analysis measured CD31 and CD34 expression, and immunofluorescence analysis measured von Willebrand factor and VEGF receptor 2 expression in ELCs. Ultrasound biomicroscopy observed a significantly increased intima-media thickness in the phosphate-buffered saline (PBS) and BM-MSCs groups compared with the ELCs group. Intima/media ratios were significantly reduced in the ELCs group compared with the PBS and BM-MSCs groups. At 4 weeks of administration, the cells labeled with BrdU were abundantly located in the adventitial region and neointima. MSCs were able to differentiate into ELCs in vitro. Cell therapy with BM-MSCs was not able to attenuate neointima thickness, however transplantation with ELCs significantly suppressed intimal hyperplasia following vascular injury.