Genetic modifications of bonemarrow derived human mesenchymal stem cells (hMSCs) using microRNAs (miRs) may be used to\nimprove their therapeutic potential and enable innovative strategies in tissue regeneration.However, most of the studies use cultured\nhMSCs, although these can lose their stem cell characteristics during expansion. Therefore, we aimed to develop a nonviral miR\ncarrier based on polyethylenimine (PEI) bound to magnetic nanoparticles (MNPs) for efficient miR delivery in freshly isolated\nhMSCs. MNP based transfection is preferable for genetic modifications in vivo due to improved selectivity, safety of delivery, and\nreduced side effects.Thus, in this study different miR/PEI and miR/PEI/MNP complex formulations were tested in vitro for uptake\nefficiency and cytotoxicity with respect to the influence of an external magnetic field. Afterwards, optimized magnetic complexes\nwere selected and compared to commercially available magnetic vectors (Magnetofectamine, CombiMag).We found that all tested\ntransfection reagents had high miR uptake rates (yielded over 60%) and no significant cytotoxic effects. Our work may become\ncrucial for virus-free introduction of therapeutic miRs as well as other nucleic acids in vivo.Moreover, in the field of targeted stem\ncell therapy nucleic acid delivery prior to transplantation may allowfor initial cell modulation in vitro.
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