Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China; Department of Clinical Nursing, School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China; Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, 210096, China.
Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
Exp Cell Res. 2019 Oct 1;383(1):111492. doi: 10.1016/j.yexcr.2019.07.005. Epub 2019 Jul 7.
Endothelial-mesenchymal transition (EndoMT) is a key step during lung fibrosis. Studies have shown that bone marrow mesenchymal stem cells (BMSCs) may act as therapeutic candidates for lung fibrosis. However, the effects of BMSCs on EndoMT induced by SiO have not been elucidated, and means to label and track grafted cells have been lacking. The current study explored whether BMSCs prevented pulmonary fibrosis by targeting EndoMT, as well as analyzed the distribution of BMSCs labeled with superparamagnetic iron oxide (SPIO) nanoparticles during treatment. TIE2-GFP mice, human umbilical vein endothelial cells (HUVECs), and BMSCs labeled with SPIO nanoparticles were used to explore the distributions and therapeutic effects of BMSCs in vivo and in vitro. We found that BMSCs reversed lung fibrosis by targeting EndoMT in vivo. Furthermore, we show that BMSCs labeled with SPIO nanoparticles could be used to track stem cells reliably in the lungs for 14 days. Conditioned medium from BMSCs attenuated the increased functional changes and reversed the SiO-induced upregulation of ER stress and autophagy markers irrespective of whether they were nanoparticle labeled or not. Our findings identify novel methods to track labeled BMSCs with therapeutic potential.
内皮-间质转化（EndoMT）是肺纤维化过程中的一个关键步骤。研究表明，骨髓间充质干细胞（BMSCs）可能作为肺纤维化的治疗候选物。然而，BMSCs 对二氧化硅（SiO）诱导的 EndoMT 的影响尚未阐明，且缺乏对移植细胞进行标记和跟踪的手段。本研究探讨了 BMSCs 是否通过靶向 EndoMT 来预防肺纤维化，并分析了超顺磁性氧化铁（SPIO）纳米颗粒标记的 BMSCs 在治疗过程中的分布。使用 TIE2-GFP 小鼠、人脐静脉内皮细胞（HUVECs）和 SPIO 纳米颗粒标记的 BMSCs 来探索 BMSCs 在体内和体外的分布和治疗效果。我们发现，BMSCs 通过在体内靶向 EndoMT 来逆转肺纤维化。此外，我们表明，SPIO 纳米颗粒标记的 BMSCs 可用于在肺部可靠地跟踪干细胞长达 14 天。BMSCs 的条件培养基可减轻功能变化的增加，并逆转 SiO 诱导的 ER 应激和自噬标志物的上调，无论是否进行了纳米颗粒标记。我们的研究结果确定了跟踪具有治疗潜力的标记 BMSCs 的新方法。
