The use of BDNF to enhance the patency rate of small-diameter tissue-engineered blood vessels through stem cell homing mechanisms
The use of BDNF to enhance the patency rate of small-diameter tissue-engineered blood vessels through stem cell homing mechanisms
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利用BDNF通过干细胞归巢机制提高小直径组织工程血管的通畅率
DOI：
10.1016/j.biomaterials.2011.09.066
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发表时间：
2012-01-01
期刊：
影响因子：
14
通讯作者：
Zhu, Chuhong
中科院分区：
文献类型：
--
作者：
Zeng, Wen;Wen, Can;Zhu, Chuhong
小直径组织工程血管的通畅率是其在冠状动脉搭桥术中应用的决定因素。冠状动脉受迷走神经支配。迷走神经的起源富含脑源性神经营养因子（BDNF）。我们研究了 BDNF 是否可以通过促进干细胞归巢和旁分泌活性来提高小直径组织工程血管的通畅率。在体外，我们分离了早期和晚期内皮祖细胞（EPC），发现BDNF可以促进EPC的单克隆形成和旁分泌功能，并且还可以诱导晚期EPC的增殖、迁移和分化。 BDNF 可以增强平行板流动室中 EPC 的捕获。流式细胞术分析和激光扫描共聚焦显微镜显示BDNF可以增强C57BL/6小鼠EPC在金属丝损伤后的动员和归巢。在此基础上，通过SPDP将BDNF偶联至胶原蛋白孵育的血管基质材料的管腔表面，构建BDNF修饰的小直径组织工程血管。大鼠植入后8周血管通畅率明显高于对照组，内皮化水平优于对照组。这些结果表明，BDNF可以通过干细胞归巢和旁分泌有效改善小直径组织工程血管的通畅性，有望在冠状动脉旁路移植替代品的构建中发挥重要作用。 (C) 2011 Elsevier Ltd. 保留所有权利。
The patency rate of small-diameter tissue-engineered blood vessels is the determinant for their application in coronary artery bypass grafting. The coronary artery is innervated by vagus nerves. The origin of vagus nerves is rich in brain-derived neurotrophic factors (BDNF). We have investigated whether BDNF could improve the patency rate of small-diameter tissue-engineered blood vessels through promoting stem cell homing and paracrine activity. In vitro, we isolated early and late endothelial progenitor cells (EPCs) and found BDNF could promote single clone formation and paracrine function of EPCs, and could also induce the proliferation, migration and differentiation of late EPCs. BDNF could enhance the capturing of EPCs in parallel-plate flow chamber. Flow cytometric analysis and laser-scanning confocal microscope showed BDNF could enhance the mobilization and homing of C57BL/6 mouse EPCs after wire injury. Based on it, BDNF was coupled to the lumen surface of the blood vessel matrix material incubated with collagen through SPDP to construct BDNF-modified small-diameter tissue-engineered blood vessel. The blood vessel patency rate was significantly higher than that of control group 8 weeks after implantation in rats and the endothelialization level was superior to control. These results demonstrate that BDNF can effectively improve patency of small-diameter tissue-engineered blood vessels through stem cell homing and paracrine, and it is expected to play an important role in the construction of substitutes for coronary artery bypass grafting. (C) 2011 Elsevier Ltd. All rights reserved.