Title | Human umbilical cord blood-derived endothelial cells reendothelialize vein grafts and prevent thrombosis. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | MA Brown, L Zhang, VW Levering, J-H Wu, LL Satterwhite, L Brian, NJ Freedman, and GA Truskey |
Journal | Arterioscler Thromb Vasc Biol |
Volume | 30 |
Start Page | 2150 |
Issue | 11 |
Pagination | 2150 - 2155 |
Date Published | 11/2010 |
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. CONCLUSIONS: 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. |
DOI | 10.1161/ATVBAHA.110.207076 |
Short Title | Arterioscler Thromb Vasc Biol |