Enhanced Anti‐inflammatory Capacity of the Conditioned Medium Derived from Periodontal Ligament Stem Cells Modified with an Iron‐Based Nanodrug

Abstract Cell‐free therapy using conditioned medium (CM) from mesenchymal stem cells takes full advantage of the bioactive factors secreted by the cells while avoiding disadvantages such as immune rejection and tumor formation due to cell transplantation. In this study, human periodontal ligament stem cells (PDLSCs) are modified with the superparamagnetic iron oxide nanoparticle (SPION)‐based nanodrug ferumoxytol (PDLSC‐SPION). Compared with PDLSCs, PDLSC‐SPION showed good cell viability and better osteogenic differentiation ability. Cell‐free CM is collected and the anti‐inflammatory capacity of PDLSC CM and PDLSC‐SPION CM is assessed by treatment of lipopolysaccharide‐stimulated macrophages and IL‐17‐stimulated human gingival fibroblasts. Both CMs inhibited the expression of proinflammatory cytokines in cells, and the therapeutic effect is more distinct for PDLSC‐SPION CM than PDLSC CM, which may be due to their different proteomic compositions. Therefore, modification of PDLSCs with ferumoxytol enhances the anti‐inflammatory capacity of its CM, making it more potentially useful for the treatment of inflammatory diseases such as periodontitis.