Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing University, Chongqing, China.
Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
J Biomed Mater Res A. 2023 Sep;111(9):1344-1357. doi: 10.1002/jbm.a.37534. Epub 2023 Mar 20.
Though magnetic iron oxide nanoparticles (IONPs) are approved for clinical use as contrast agents for MR imaging in United States and Europe, and are widely used to label cells in research, the relationship between IONPs and mesenchymal stem cells (MSCs) is not fully addressed. Here the effects of consistently appeared γ-Fe O on the lineage commitment of MSCs were studied to optimize applications of IONPs in MSCs upon verification of viability. 30 nm 10 μg/mL induced highest promotions on osteogenesis, while 30 and 50 nm of 100 μg/mL elicited most chondrogensis in 14 days, where the effects on ALP, GAG and SOX9 appeared after 7 days, while on RUNX2 came out after 10 days. γ-Fe O enhanced intracellular and extracellular Fe and ROS, modulated F-actin and decreased Lamin A of MSCs at different time scale. The disturbances of F-actin, Lamin A or ROS altered the effects of γ-Fe O on MSC differentiation. Our results demonstrate that different size, concentration and modulation of γ-Fe O are needed in its MSC applications for bone and cartilage tissues. Furthermore, an undocumented phenomenon that the modulation of F-actin affected the Lamin A expression in MSCs was observed.
尽管磁性氧化铁纳米颗粒 (IONPs) 已被批准在美国和欧洲作为磁共振成像的对比剂用于临床,并且广泛用于研究中的细胞标记,但 IONPs 与间充质干细胞 (MSCs) 之间的关系尚未完全阐明。在这里,研究了一致出现的 γ-FeO 对 MSCs 谱系分化的影响,以在验证细胞活力后优化 IONPs 在 MSCs 中的应用。30nm 10μg/mL 诱导的成骨作用最高,而 30nm 和 50nm 的 100μg/mL 在 14 天内诱导出最高的软骨生成,其中 ALP、GAG 和 SOX9 的作用在 7 天后出现,而 RUNX2 的作用在 10 天后出现。γ-FeO 增强了细胞内和细胞外的 Fe 和 ROS,调节了 F-肌动蛋白并减少了 MSCs 的 Lamin A 在不同时间尺度上的表达。F-肌动蛋白、Lamin A 或 ROS 的紊乱改变了 γ-FeO 对 MSC 分化的影响。我们的结果表明,在骨和软骨组织的 MSC 应用中需要不同的大小、浓度和 γ-FeO 调节。此外,还观察到一个未记录的现象,即 F-肌动蛋白的调节影响了 MSCs 中的 Lamin A 表达。