Targeted migration of bone marrow mesenchymal stem cells inhibits silica-induced pulmonary fibrosis in rats
Targeted migration of bone marrow mesenchymal stem cells inhibits silica-induced pulmonary fibrosis in rats
复制标题
骨髓间充质干细胞的靶向迁移抑制二氧化硅诱导的大鼠肺纤维化
DOI：
10.1186/s13287-018-1083-y
复制
发表时间：
2018-12-04
影响因子：
7.5
通讯作者：
Tian, Lin
中科院分区：
文献类型：
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作者：
Li, Xiaoli;An, Guoliang;Tian, Lin
背景：矽肺是一种常见的职业病，以矽肺结节和弥漫性肺纤维化为特征。我们证明了骨髓间充质干细胞（BMSCs）在二氧化硅诱导的肺纤维化中的抗纤维化作用。在本研究中，我们试图澄清归巢能力的骨髓基质细胞和其effects.Methods和结果的具体机制：的生物分布的骨髓基质细胞的近红外荧光（NIRF）成像确定在体内和体外。结果显示，用NIR-DiR染料标记的BMSC靶向二氧化硅损伤的肺组织，其中它们在注射后6小时达到峰值，并在第3天急剧下降。基于这些发现，在第一次注射后3天进行第二次BMSC注射。注射的BMSCs迁移到受损的肺，但没有转化为特定的肺细胞类型。有趣的是，BMSC条件培养基（BMSCs-CM）的注射显着减弱二氧化硅诱导的肺纤维化。BMSCs-CM处理组大鼠肺组织胶原沉积减少，肺结节数目减少。与这些发现平行的是，与二氧化硅组相比，BMSCs-CM处理组中I型胶原、III型胶原和纤连蛋白的mRNA水平以及转化生长因子（TGF）-β 1和羟脯氨酸的含量降低。此外，肺泡上皮细胞标志物上调BMSCs-CM treatment.Conclusions：骨髓间充质干细胞迁移到损伤区的肺二氧化硅灌注后，减弱肺纤维化。骨髓间充质干细胞的抗纤维化作用主要是通过旁分泌方式发挥的，而不是通过其分化能力发挥的。
Background: Silicosis is a common occupational disease, characterized by silicotic nodules and diffuse pulmonary fibrosis. We demonstrated an anti-fibrotic effect of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung fibrosis. In the present study, we sought to clarify the homing ability of BMSCs and the specific mechanisms for their effects.Methods and results: The biodistribution of BMSCs was identified by near-infrared fluorescence (NIRF) imaging in vivo and in vitro. The results showed that BMSCs labeled with NIR-DiR dyes targeted silica-injured lung tissue, wherein they reached a peak at 6 h post-injection and declined dramatically by day 3. Based on these findings, a second injection of BMSCs was administered 3 days after the first injection. The injected BMSCs migrated to the injured lungs, but did not undergo transformation into specific lung cell types. Interestingly, the injection of BMSC-conditioned medium (BMSCs-CM) significantly attenuated silica-induced pulmonary fibrosis. The collagen deposition and number of nodules were decreased in lung tissues of BMSCs-CM-treated rats. In parallel with these findings, the mRNA levels of collagen I, collagen III, and fibronectin, and the content of transforming growth factor (TGF)-beta 1 and hydroxyproline were decreased in the BMSCs-CM-treated group compared with the silica group. In addition, alveolar epithelial markers were upregulated by BMSCs-CM treatment.Conclusions: BMSCs migrated to injured areas of the lung after silica instillation and attenuated pulmonary fibrosis. The anti-fibrotic effects of BMSCs were mainly exerted in paracrine manner, rather than through their ability to undergo differentiation.