ENDOTHELIAL-LIKE CELLS DERIVED FROM MESENCHYMAL STEM CELLS ATTENUATE NEOINTIMAL HYPERPLASIA AFTER VASCULAR INJURY: PP.21.339

Abstract

Objectives: The present study investigates the contribution of mesenchymal stem cells (MSCs) to neointimal formation, and whether endothelial-like cells differentiated from MSCs could attenuate intimal hyperplasia after vascular injury. Methods: Bone marrow-derived MSCs of SD rats were cultured in vitro routinely. Differentiation into endothelial-like cells was induced by cultivation of confluent cells in the presence of 50ng/ml vascular endothelial growth factor(VEGF). MSCs and endothelial-like cells were incubated with 20umol/L BrdU in 48 h for cells labeling. The labeling cells were injected via femoral vein on the day of balloon-induced carotid artery injury. Carotid arteries of all rats were examined by ultrasound biomicroscopy at day 7, 14 and 28 after the injury. Results: Flow cytometer analysis showed increased expression of CD31 and CD34, immunofluorescence analysis showed expression of endothelial-specific markers like vWF and VEGFR2 in endothelial-like cells. Ultrasound biomicroscopy showed significantly increases of IMT in the groups of PBS and MSCs compaired with endothelial-like cells group in 14 days after artery injured (0.10±0.02 mm vs 0.14±0.03 mm vs 0.13±0.02 mm, p < 0.01) and IMT significantly increased in 28 days after injury (0.16±0.02 mm vs 0.22±0.04 mm vs 0.23±0.05 mm, p < 0.01). Intimal/media (I/M) ratio were significantly reduced in endothelial-like cells group compared to PBS and MSCs groups (1.22±0.23 vs 2.52±0.64 vs 2.87±0.40, p < 0.001)(fig.1). Immunohistochemistry staining with anti-Brdu, a lot of Brdu-labeling cells were found in the adventitia, especially in the zone about vasa vasorum and few in the neointimal. Conclusions: These findings suggested that MSCs were able to differentiate into endothelial-like cells in vitro and cell therapy with MSCs could not attenuate the thickness of the neointima. Transplantation with endothelial-like cells derived from MSCs significantly suppressed intimal hyperplasia after vascular injury. A lot of transplanting cells were homing to adventitia.