Exosomes from mesenchymal stem cells expressing miR-125b inhibit neointimal hyperplasia via myosin IE

Abstract

Intercellular communication between mesenchymal stem cells (MSCs) and their target cells in the perivascular environment is modulated by exosomes derived from MSCs. However, the potential role of exosome-mediated microRNA transfer in neointimal hyperplasia remains to be investigated. To evaluate the effects of MSC-derived exosomes (MSC-Exo) on neointimal hyperplasia, their effects upon vascular smooth muscle cell (VSMC) growth in vitro and neointimal hyperplasia in vivo were assessed in a model of balloon-induced vascular injury. Our results showed that MSC-Exo were internalised by VSMCs and inhibited proliferation and migration in vitro. Further analysis revealed that miR-125b was enriched in MSC-Exo, and repressed the expression of myosin 1E (Myo1e) by targeting its 3ʹ untranslated region. Additionally, MSC-Exo and exosomally transferred miR-125b repressed Myo1e expression and suppressed VSMC proliferation and migration and neointimal hyperplasia in vivo. In summary, our findings revealed that MSC-Exo can transfer miR-125b to VSMCs and inhibit VSMC proliferation and migration in vitro and neointimal hyperplasia in vivo by repressing Myo1e, indicating that miR-125b may be a therapeutic target in the treatment of vascular diseases.