Biophysics Group, Department of Physics and Astronomy, University College London, Gower Street, London, WC1E 6BT, UK.
UCL Healthcare and Biomagnetics and Nanomaterials Laboratory, 21 Albemarle Street, London, W1S 4BS, UK.
Sci Rep. 2017 Aug 10;7(1):7850. doi: 10.1038/s41598-017-08092-w.
Stem cell tracking in cellular therapy and regenerative medicine is an urgent need, superparamagnetic iron oxide nanoparticles (IONPs) could be used as contrast agents in magnetic resonance imaging (MRI) that allows visualization of the implanted cells ensuring they reach the desired sites in vivo. Herein, we report the study of the interaction of 3,4-dihydroxyhydrocinnamic acid (DHCA) functionalized IONPs that have desirable properties for T - weighted MRI, with bone marrow-derived primary human mesenchymal stem cells (hMSCs). Using the multiparametric high-content imaging method, we evaluate cell viability, formation of reactive oxygen species, mitochondrial health, as well as cell morphology and determine that the hMSCs are minimally affected after labelling with IONPs. Their cellular uptake is visualized by transmission electron microscopy (TEM) and Prussian Blue staining, and quantified using an iron specific colourimetric method. In vitro and in vivo studies demonstrate that these IONPs are biocompatible and can produce significant contrast enhancement in T-weighted MRI. Iron oxide nanoparticles are detected in vivo as hypointense regions in the liver up to two weeks post injection using 9.4 T MRI. These DHCA functionalized IONPs are promising contrast agents for stem cell tracking by T-weighted MRI as they are biocompatible and show no evidence of cytotoxic effects on hMSCs.
细胞治疗和再生医学中的干细胞示踪是一项紧迫的需求，超顺磁性氧化铁纳米粒子（IONPs）可用作磁共振成像（MRI）中的对比剂，能够可视化植入的细胞，确保它们在体内到达预期的部位。在此，我们报告了 3,4-二羟基肉桂酸（DHCA）功能化 IONPs 与骨髓来源的原代人骨髓间充质干细胞（hMSCs）相互作用的研究。使用多参数高内涵成像方法，我们评估了细胞活力、活性氧的形成、线粒体健康以及细胞形态，并确定 hMSCs 在标记 IONPs 后受影响最小。通过透射电子显微镜（TEM）和普鲁士蓝染色观察到它们的细胞摄取，并使用铁特异性比色法进行定量。体外和体内研究表明，这些 IONPs 具有生物相容性，并可在 T 加权 MRI 中产生显著的对比增强。使用 9.4T MRI，在注射后两周内，这些 IONPs 在肝脏中作为低信号强度区域被体内检测到。这些 DHCA 功能化的 IONPs 是用于 T 加权 MRI 干细胞示踪的有前途的对比剂，因为它们具有生物相容性，并且对 hMSCs 没有显示出细胞毒性作用的证据。
