a Department of Prenatal Diagnostic Center , Guangzhou Women and Children's Medical Centre, Guangzhou Medical University , Guangzhou , People's Republic of China.
b State Key Laboratory of Oncology in South China , Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine , Guangzhou , People's Republic of China.
Artif Cells Nanomed Biotechnol. 2018;46(sup3):S18-S27. doi: 10.1080/21691401.2018.1489260. Epub 2018 Jul 22.
Early evaluation of iron overload (IO) and prompt iron-chelation therapy reduce the haematopoietic damage wrought by IO-induced reactive oxygen species (ROS). We examined whether MagA could simultaneously increase the sensitivity of magnetic resonance imaging (MRI) for iron measurement and attenuate oxidative damage to the haematopoietic microenvironment. After generation of a transgenic (Tg) mouse model, MRI, transmission electron microscopy and cytotoxicity assays were used to assess various parameters in mesenchymal stem cells (MSCs). Transverse relaxation rate (R2*) of MagA-expressing MSCs in the presence of iron supplement was higher compared with that of control cells. Besides, R2* value of liver from IO magA Tg mice was higher than that of wild type mice. Moreover, MagA contributed to reduce the cytotoxicity of iron against MSCs, reduce expression of p-p38 mitogen-activated protein kinase and ferritin, and reduce inhibition of the osteogenic differentiation caused by IO. These data support the use of magA as a reporter gene for cell tracking with MRI and indicate exciting new possibilities for use of MagA in the attenuation of injury due to oxidative stress caused by exogenous iron.
早期评估铁过载（IO）并及时进行铁螯合治疗，可减轻由 IO 诱导的活性氧（ROS）引起的造血损伤。我们研究了 MagA 是否可以同时提高磁共振成像（MRI）测量铁的敏感性，并减轻对造血微环境的氧化损伤。在生成转基因（Tg）小鼠模型后，使用 MRI、透射电子显微镜和细胞毒性测定来评估间充质干细胞（MSCs）中的各种参数。在补充铁的情况下，表达 MagA 的 MSC 的横向弛豫率（R2*）高于对照细胞。此外，IO MagA Tg 小鼠肝脏的 R2* 值高于野生型小鼠。此外，MagA 有助于降低铁对 MSC 的细胞毒性，降低 p-p38 丝裂原活化蛋白激酶和铁蛋白的表达，并降低 IO 引起的成骨分化抑制。这些数据支持使用 MagA 作为 MRI 细胞示踪的报告基因，并为 MagA 在减轻由外源性铁引起的氧化应激引起的损伤方面的应用提供了令人兴奋的新可能性。
