Department of Anatomy, Key Lab for Biomechanics of Chongqing, Third Military Medical University, Gao Tan Yan Street, Shaping Ba District, Chongqing 400038, China.
Biomaterials. 2010 Mar;31(7):1636-45. doi: 10.1016/j.biomaterials.2009.11.037. Epub 2009 Dec 16.
Endothelial progenitor cells (EPCs) mobilization and homing are critical to the development of an anti-thrombosis and anti-stenosis tissue-engineered blood vessel. The growth and activation of blood vessels are supported by nerves. We investigated whether nerve growth factors (NGF) can promote EPCs mobilization and endothelialization of tissue-engineered blood vessels. In vitro, NGF promoted EPCs to form more colonies, stimulated human EPCs to differentiate into endothelial cells, and significantly enhanced EPCs migration. Flow cytometric analysis revealed that NGF treatment increased the number of EPCs in the peripheral circulation of C57BL/6 mice. Furthermore, the treatment of human EPCs with NGF facilitated their homing into wire-injured carotid arteries after injection into mice. Decellularized rat blood vessel matrix was incubated with EDC cross-linked collagen and bound to NGF protein using the bifunctional coupling agent N-succinmidyl3-(2-pyridyldit-hio) propionate (SPDP). The NGF-bound tissue-engineered blood vessel was implanted into rat carotid artery for 1 week and 1 month. NGF-bound blood vessels possessed significantly higher levels of endothelialization and patency than controls did. These results demonstrated that NGF can markedly increase EPCs mobilization and homing to vascular grafts. Neurotrophic factors such as NGF have a therapeutic potential for the construction of tissue-engineered blood vessels in vivo.
内皮祖细胞（EPCs）的动员和归巢对于形成抗血栓和抗狭窄的组织工程血管至关重要。血管的生长和激活受到神经的支持。我们研究了神经生长因子（NGF）是否可以促进 EPCs 的动员和组织工程血管的内皮化。在体外，NGF 促进 EPCs 形成更多的集落，刺激人 EPCs 分化为内皮细胞，并显著增强 EPCs 的迁移。流式细胞术分析显示，NGF 处理增加了 C57BL/6 小鼠外周循环中 EPCs 的数量。此外，NGF 处理人 EPCs 后，促进其归巢到注射到小鼠体内的钢丝损伤颈动脉。脱细胞大鼠血管基质与 EDC 交联胶原孵育，并使用双功能偶联剂 N-琥珀酰亚胺基 3-(2-吡啶二硫代)丙酸酯（SPDP）将 NGF 蛋白结合到基质上。将 NGF 结合的组织工程血管植入大鼠颈动脉 1 周和 1 个月。与对照组相比，NGF 结合的血管具有更高水平的内皮化和通畅率。这些结果表明，NGF 可以显著增加 EPCs 向血管移植物的动员和归巢。神经营养因子如 NGF 具有治疗体内组织工程血管构建的潜力。
