NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi 54, India; Division of Stem Cell and Gene Therapy Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi 54, India.
NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi 54, India.
Toxicol In Vitro. 2018 Aug;50:179-189. doi: 10.1016/j.tiv.2018.03.009. Epub 2018 Mar 22.
The use of iron oxide nanoparticles for different biomedical applications, hold immense promise to develop negative tissue contrast in magnetic resonance imaging (MRI). Previously, we have optimized the labelling of mesenchymal stem cells (MSCs) with iron oxide nanoparticles complexed to different transfection agents like poly-l-lysine (IO-PLL) and protamine sulfate (Fe-Pro) on the basis of relaxation behaviour and its biological expressions. However, there is a distinct need to investigate the biocompatibility and biosafety concerns coupled with its cytotoxicity and genotoxicity. This study was prepared to evaluate the viability of cells, generation of ROS, changes in actin cytoskeleton, investigation of cell death, level of GSH and TAC, activities of SOD and GPx, and stability of DNA in MSCs after labelling. Results demonstrated a marginal alteration in toxicological parameters like ROS generation, cell length, actin cytoskeleton, total apoptosis and DNA damage was detected after stem cell labelling. Insignificant depletion of GSH and SOD level, and increase in GPx and TAC level in MSCs were measured after labelling with IO-PLL and Fe-Pro complexes, which later on recovered and normalized to its baseline. This MSCs labelling could provide a reference guideline for toxicological analysis and relaxometry based in vivo MRI detection.
氧化铁纳米颗粒在不同的生物医学应用中具有很大的应用潜力,可以在磁共振成像(MRI)中开发负组织对比。以前,我们已经根据弛豫行为及其生物学表达,优化了用不同转染剂(如聚赖氨酸(IO-PLL)和硫酸鱼精蛋白(Fe-Pro))复合的间充质干细胞(MSCs)的标记。然而,有必要研究其细胞毒性和遗传毒性与其生物相容性和生物安全性问题。这项研究旨在评估细胞活力、ROS 的产生、肌动蛋白细胞骨架的变化、细胞死亡的调查、GSH 和 TAC 的水平、SOD 和 GPx 的活性以及 MSC 中 DNA 的稳定性在标记后。结果表明,在干细胞标记后,ROS 生成、细胞长度、肌动蛋白细胞骨架、总凋亡和 DNA 损伤等毒理学参数有轻微改变。在 IO-PLL 和 Fe-Pro 复合物标记后,MSCs 中 GSH 和 SOD 水平显著降低,GPx 和 TAC 水平升高,但后来恢复并恢复到基线水平。这种 MSC 标记可以为基于体内 MRI 检测的毒理学分析和弛豫率提供参考指南。