Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2150-5. doi: 10.1161/ATVBAHA.110.207076. Epub 2010 Aug 26.
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.
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.
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.
通过输注人脐血源性内皮细胞(hCB-EC)来加速静脉移植物再内皮化并减少静脉移植物血栓形成,因为内皮细胞的丧失会导致静脉移植物血栓形成和新生内膜增生。
在体外稳定流动条件下,hCB-EC 与平滑肌细胞的黏附率比外周血或人主动脉衍生的 EC 高 2.5 至 13 倍(P<0.05)。与外周血和人主动脉 EC 相比,hCB-EC 每个细胞的细胞表面α(5)β(1)整联蛋白异二聚体多 1.4 倍(P<0.05),在纤连蛋白上的增殖速度快 4 至 10 倍(P<0.05)。因此,我们使用 hCB-EC 增强植入 NOD.CB17-Prkdc(scid)/J 小鼠的颈动脉间置静脉移植物的再内皮化。术后 2 周,hCB-EC 处理的小鼠的静脉移植物显示出约 55%的再内皮化,没有管腔血栓形成。相比之下,来自 sham 处理的小鼠的静脉移植物在 75%的标本中显示出管腔血栓形成(P<0.05),仅显示出约 14%的再内皮化。在 hCB-EC 处理的小鼠的静脉移植物中,通过人主要组织相容性复合体 I 表达判断,有 33±10%的内皮来源于人类。
hCB-EC 在体外流动条件下黏附于平滑肌细胞,在体内加速静脉移植物再内皮化,并防止静脉移植物血栓形成。因此,hCB-EC 为静脉移植物疾病提供了新的治疗可能性。