The role of fucosylation in the promotion of endothelial progenitor cells in neovascularization and bone repair
The role of fucosylation in the promotion of endothelial progenitor cells in neovascularization and bone repair
复制标题
岩藻糖基化在促进内皮祖细胞新生血管形成和骨修复中的作用。
DOI：
10.1016/j.biomaterials.2014.01.025
复制
发表时间：
2014-04-01
期刊：
影响因子：
14
通讯作者：
Dong，Ningzheng
中科院分区：
文献类型：
--
作者：
Sun，Shengxuan;Liu，Zhenzhen;Dong，Ningzheng
骨髓来源的内皮祖细胞（EPCs）正在被测试作为治疗各种缺血性疾病的疗法。对靶组织的不良归巢是限制EPCs治疗功效的主要因素之一。在这里，我们表明，人脐带血来源的EPCs表达唾液酸刘易斯X（sLex）抗原，这是必要的选择素介导的细胞-细胞相互作用。在EPCs中表达α 1，3-岩藻糖基转移酶VI（FucT VI）可增强sLexsynthesis，E-和P-选择素结合，以及EPC与培养的肿瘤坏死因子-α刺激的人脐静脉内皮细胞的粘附。在静脉注射EPCs的后肢缺血小鼠模型中，FucT VI表达增加了缺血肌肉中的EPC归巢、新血管形成和血流量。在另一种小鼠股骨骨折模型中，表达FucT VI的EPCs在靶向骨折周围组织以增强血管生成、血流和骨修复方面比对照EPCs更有效。这些结果表明岩藻糖基化的EPCs可以作为一种改善的细胞来源来治疗缺血性疾病。
Bone marrow-derived endothelial progenitor cells (EPCs) are being tested as a therapy to treat a variety of ischemic diseases. Poor homing to targeted tissues is one of the major factors limiting the therapeutic efficacy of EPCs. Here, we show that human cord blood-derived EPCs expressed little sialyl Lewis X (sLex) antigen that is necessary for selectin-mediated cell–cell interactions. Expression of α1,3-fucosyltransferase VI (FucT VI) in the EPCs enhanced sLexsynthesis, E- and P-selectin-binding, and EPC adhesion to tumor necrosis factor-α-stimulated human umbilical vein endothelial cells in culture. In a mouse model of hind limb ischemia, in which EPCs were injected intravenously, FucT VI expression increased EPC homing, neovascularization, and blood flow in ischemic muscles. In another mouse model of femoral fracture, FucT VI-expressing EPCs were more efficient than control EPCs in targeting to peri-fracture tissues to enhance angiogenesis, blood flow and bone repair. These results indicate that fucosylated EPCs may be used to as an improved cellular source to treat ischemic diseases.