Dextran-coated iron oxide nanoparticles turn protumor mesenchymal stem cells (MSCs) into antitumor MSCs

[[abstract]]Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) with the tumor tropism have shown promise as a cellular deliverer of anticancer agents for cancer therapy. However, despite the fact that engineered MSCs have demonstrated profound anticancer effects, the exact intrinsic impact of MSCs themselves on tumor progression is still being debated. Therefore, in order to ensure pertinent MSC-based cancer therapy, it is essential to further explore the intrinsic antitumor and protumor effects of MSCs on tumor progression. Here, we show that dextran-coated iron oxide nanoparticles can not only increase the antitumor effect of native antitumor MSCs but also reverse the protumor effect of native protumor MSCs and hence turn protumor MSCs into antitumor MSCs in vivo, which can be attributed to the in vitro finding that dextran-coated iron oxide nanoparticles can not only inhibit the colony formation of cancer cells likely through induction of cytokine receptor expression to competitively capture the tumorous cytokine but also diminish cancer-mediated fibroblast differentiation and angiogenesis of protumor MSCs. This is the first report to demonstrate the induction of antitumor MSCs from protumor MSCs