P78	Transfer of stem cell-derived endothelial cells retarded neointimal lesions in the injured artery.
1Q.Xiao, 1Z.Zhang, 1L.Zeng, 2Z.Ali, 2K.M.Channon, 1Y.Hu, 1Q.Xu
1St George's University of London, London, GB; 2University of Oxford, Oxford, GB.

Background – Embryonic stem (ES) cells have the ability to differentiate into somatic cells of all tissue types, which can be used for tissue engineering and repair of damaged organs. However, no successful procedure for producing a large number of endothelial cells (ECs) from ES cells with high purity is available, and little is known about the therapeutic potential for these stem cell-derived ECs in repairing injured artery. Methods and Results – Mouse ES cells were cultivated on collagen-IV-coated flasks, and Sca-1+ progenitor cells were then isolated with magnetic beads. The isolated cells were cultured in DM medium containing 10ng/ml VEGF165 for 6 to 21 days. RT-PCR, immunofluorescence or Western blot analysis revealed that these cells expressed a full range of EC lineage-specific markers, including CD31 (PECAM-1), CD34, CD62E (E-selectin), CD105, CD106 (VCAM-1), CD109, CD141, CD144 (VE-cadherin), CD146, Flk-1 (VEGFR2), Flt-1 (VEGFR1), Sca-1, Tie1/2, and von Willbrand factor. Flow cytometry analysis confirmed that 98.7% of the cells were CD31 positive, and almost all the cells were DiI-acLDL uptake. When Sca-1+ progenitor-derived ECs mixed with Matrigel were subcutaneously implanted into mice, various vessel-like structures were observed. Furthermore, when these ECs infected with adenovirus-LacZ were transplanted into injured mouse artery, they were found to form neo-endothelium that covered the injured areas (86%±13.6%). This cell transplantation resulted in a significant decrease in neointima lesions 2 weeks after injury (8,036 mm2±866 mm2 vs 30,026 mm2±2500 mm2, p<0.001). Conclusions – We conclude that Sca-1+ progenitor cells derived from ES cells can differentiate into functional ECs, which accelerate reendothelialization of injured artery and reduce neointimal formation. These results indicate that these ECs may serve as a promising cellular source for vascular tissue engineering and cell therapy for vascular diseases.

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