Ru nanoparticles coated with γ-Fe2O3 promoting and monitoring the differentiation of human mesenchymal stem cells via MRI tracking.

Abstract

Human mesenchymal stem cells (MSCs) can be successively passaged and can differentiate into multiple lineages. These attributes are important in tissue engineering, which has a great deal of attention in stem cell therapy. However, the effective labelling and tracking of MSCs in vivo remain major unresolved issues. Based on the use of iron oxides to label stem cells for magnetic resonance imaging (MRI), we synthesized nanoparticle (NPs) containing ruthenium (RuNPs), γ-Fe2O3@Ru (Fe2O3@Ru), and γ-Fe2O3@selenium (Fe2O3@Se) to label MSCs and promote osteogenic differentiation. Fe2O3@Ru and Fe2O3@Se could be used as T2-weighted MRI contrast agents. Fe2O3@Ru more effectively diffused in the cytoplasm and localized in the nuclei of MSCs, compared with Fe2O3@Se. RuNPs, Fe2O3@Ru, and Fe2O3@Se induced MSCs to differentiate into osteoblasts. Fe2O3@Ru, in particular, was a potent osteoinductive agent. Fe2O3@Ru also inhibited adipocytic differentiation. Promotion of the osteogenic differentiation of MSCs may be regulated by a Smad-dependent bone morphogenetic protein signaling pathway with reduced expression of CD44, CD73, and CD105. MSCs treated with Fe2O3@Ru NPs expressing osteoblast surface markers.