The dependences of mesenchymal stem cells commitments on the size, concentration, internalization and exposure time of Iron Oxide Nanoparticles through F-actin, Lamin A and ROS.

Abstract

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-Fe₂ O₃ 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-Fe₂ O₃ enhanced intracellular and extracellular Fe³⁺ 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-Fe₂ O₃ on MSC differentiation. Our results demonstrate that different size, concentration and modulation of γ-Fe₂ O₃ 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.