Targeted release of stromal cell-derived factor-1α by reactive oxygen species-sensitive nanoparticles results in bone marrow stromal cell chemotaxis and homing, and repair of vascular injury caused by electrical burns.
Targeted release of stromal cell-derived factor-1α by reactive oxygen species-sensitive nanoparticles results in bone marrow stromal cell chemotaxis and homing, and repair of vascular injury caused by electrical burns.
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活性氧敏感纳米颗粒定向释放基质细胞衍生因子 1 α，导致骨髓基质细胞趋化和归巢，修复电烧伤引起的血管损伤
DOI：
10.1371/journal.pone.0194298
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Xia ZF
中科院分区：
文献类型：
--
作者：
He F;Luo PF;Tang T;Zhang F;Fang H;Ji SZ;Sun Y;Wu GS;Pan BH;Huo ZB;Wang GY;Xia ZF
血管损伤的快速修复是电烧伤预后的重要因素。这种修复主要通过基质细胞衍生因子(SDF)-1α促进骨髓间充质干细胞（BMSCs）向内皮细胞的动员、趋化、归巢和靶向分化来实现。在循环中从局部损伤部位形成浓度梯度对SDF-1α的作用至关重要。在之前的研究中，我们开发了含有SDF-1α的活性氧（ROS）敏感的PPADT纳米颗粒，该纳米颗粒可以响应组织病变中高浓度的ROS降解，从而达到靶向释放SDF-1α的目的。本研究采用电烧伤大鼠血管损伤模型，研究PPADT纳米颗粒靶向释放SDF-1α对骨髓间充质干细胞趋化性和血管损伤修复的影响。220 V连续暴露6 s可使大鼠血管内皮细胞损伤，内层脱落，局部ROS水平显著升高，SDF-1α水平显著降低。注射Cy5标记的SDF-1α- ppadt纳米颗粒后，Cy5荧光的分布表明，SDF-1α主要分布在损伤部位，局部SDF-1α水平显著升高。注射纳米颗粒损伤7天后，观察到外源性绿色荧光蛋白标记的骨髓间充质干细胞在损伤部位聚集。损伤后10 d，内皮细胞排列更整齐、连续，血管形态相对完整，血管增多。这些结果表明，SDF-1α- ppadt纳米颗粒靶向损伤部位的SDF-1α释放，指导BMSC趋化和归巢，从而促进电烧伤后血管修复。
Rapid repair of vascular injury is an important prognostic factor for electrical burns. This repair is achieved mainly via stromal cell-derived factor (SDF)-1α promoting the mobilization, chemotaxis, homing, and targeted differentiation of bone marrow mesenchymal stem cells (BMSCs) into endothelial cells. Forming a concentration gradient from the site of local damage in the circulation is essential to the role of SDF-1α. In a previous study, we developed reactive oxygen species (ROS)-sensitive PPADT nanoparticles containing SDF-1α that could degrade in response to high concentration of ROS in tissue lesions, achieving the goal of targeted SDF-1α release. In the current study, a rat vascular injury model of electrical burns was used to evaluate the effects of targeted release of SDF-1α using PPADT nanoparticles on the chemotaxis of BMSCs and the repair of vascular injury. Continuous exposure to 220 V for 6 s could damage rat vascular endothelial cells, strip off the inner layer, significantly elevate the local level of ROS, and decrease the level of SDF-1α. After injection of Cy5-labeled SDF-1α-PPADT nanoparticles, the distribution of Cy5 fluorescence suggested that SDF-1α was distributed primarily at the injury site, and the local SDF-1α levels increased significantly. Seven days after injury with nanoparticles injection, aggregation of exogenous green fluorescent protein-labeled BMSCs at the injury site was observed. Ten days after injury, the endothelial cell arrangement was better organized and continuous, with relatively intact vascular morphology and more blood vessels. These results showed that SDF-1α-PPADT nanoparticles targeted the SDF-1α release at the site of injury, directing BMSC chemotaxis and homing, thereby promoting vascular repair in response to electrical burns.
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影响因子：
--
作者：
Kimura A;Namekata K;Guo X;Noro T;Harada C;Harada T
通讯作者：
Harada T
影响因子：
4
作者：
Gomez C;Martinez L;Mesa A;Duque JC;Escobar LA;Pham SM;Vazquez-Padron RI
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Vazquez-Padron RI
影响因子：
9.5
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通讯作者：
Zou, YZ
影响因子：
5.6
作者：
Cao, Yan-jun;Zhang, Yan-min;He, Lang-chong
通讯作者：
He, Lang-chong
影响因子：
9.3
作者：
Misra, Preeti;Lebeche, Djarnel;Frangioni, John V.
通讯作者：
Frangioni, John V.