Human Umbilical Cord Blood–Derived Endothelial Cells Reendothelialize Vein Grafts and Prevent Thrombosis

Abstract

Objective— To accelerate vein graft reendothelialization and reduce vein graft thrombosis by infusing human umbilical cord blood–derived endothelial cells (hCB-ECs) because loss of endothelium contributes to vein graft thrombosis and neointimal hyperplasia. Methods and Results— Under steady flow conditions in vitro, hCB-ECs adhered to smooth muscle cells 2.5 to 13 times more than ECs derived from peripheral blood or human aorta ( P <0.05). Compared with peripheral blood and human aorta ECs, hCB-ECs had 1.4-fold more cell surface α 5 β 1 integrin heterodimers per cell ( P <0.05) and proliferated on fibronectin 4- to 10-fold more rapidly ( P <0.05). Therefore, we used hCB-ECs to enhance reendothelialization of carotid interposition vein grafts implanted in NOD.CB17-Prkdc scid /J mice. Two weeks postoperatively, vein grafts from hCB-EC–treated mice demonstrated approximately 55% reendothelialization and no luminal thrombosis. In contrast, vein grafts from sham-treated mice demonstrated luminal thrombosis in 75% of specimens ( P <0.05) and only approximately 14% reendothelialization. In vein grafts from hCB-EC–treated mice, 33±10% of the endothelium was of human origin, as judged by human major histocompatibility class I expression. Conclusion— The hCB-ECs adhere to smooth muscle cells under flow conditions in vitro, accelerate vein graft reendothelialization in vivo, and prevent vein graft thrombosis. Thus, hCB-ECs offer novel therapeutic possibilities for vein graft disease.