Synthetic bioreducible lipid‐based nanoparticles for miRNA delivery to mesenchymal stem cells to induce neuronal differentiation

MicroRNA (miRNA) functions in tissue regeneration and determines the fate of stem cells. Nanoparticle-based miRNA delivery systems for therapeutic applications have been studied in clinical settings. However, gene delivery to stem cells is still a challenging issue. Lipid-like nanoparticles produced using combinatorial approaches have recently been used for delivery of a variety of biologics. In this study, we investigated the ability of these lipids to deliver miRNA to human mesenchymal stem cells (hMSCs). First, small library screening of bioreducible lipids was performed using fluorophore-conjugated miRNA to determine the optimal chemical structure for miRNA delivery to hMSCs. Next, miRNA-9 (miR-9), which promotes neuronal differentiation of stem cells, was delivered to hMSCs using the lipids identified from the library screening. Morphological changes of the cells and upregulation of neuronal marker genes were observed after the delivery of miR-9. The synthetic bioreducible lipids are effective in facilitating miRNA delivery to hMSCs and promoting the neuronal differentiation.