Nanovector for Gene Transfection and MR Imaging of Mesenchymal Stem Cells

Abstract

This study centers on the use of superparamagnetic iron oxide nanoparticles coated with polyethylene glycol-grafted polyethylenimine (PEG-g-PEI-SPION) as an MRI-visible and efficient nanovector for the gene modification and in vivo MRI tracking of rat bone marrow-derived mesenchymal stem cells (rBMSCs). PEG-g-PEI-SPION was first condensed with plasmid DNA to form nanoparticles, demonstrating low cytotoxicity and good biocompatibility for rBMSCs. Based on a reporter gene assay, PEG-g-PEI-SPION/pDNA had the highest transfection efficiency (62.6 ± 5.5%) in rBMSCs, which was significantly higher than that obtained using the cationic liposomes in lipofectamine 2000, a commercially available and worldwide used gene transfection agent, under the most optimal conditions (13.9 ± 2.6%; P < 0 05). More excitingly, the transplantation of rBMSCs modified by our MRI-visible vector complexed with a plasmid encoding human hepatocyte growth factor into fibrotic rat livers effectively restored albumin production and significantly suppressed transaminase activities. In addition, the transplanted rBMSCs displayed a sensitive signal on T 2 /T * 2 -weighted images in vitro and in vivo, which enabled effective MRI tracking of the cells for up to 14 days post-transplantation. Although mesenchymal stem cells are well-known to be refractory in most of the current nonviral gene delivery techniques, our results demonstrate that the MRI-sensitive PEG-g-PEI-SPION is a highly efficient and readily observable nanovector for gene delivery into rBMSCs.

Efficient delivery of C/EBP beta gene into human mesenchymal stem cells via polyethylenimine-coated gold nanoparticles enhances adipogenic differentiation

“…Therefore, non-viral vectors, including inorganic nanoparticles, are emerging as attractive gene delivery vectors, because they are generally biocompatible, easily functionalized, structurally varied, and able to carry miscellaneous genetic materials 20 . Inorganic nanoparticles used for gene delivery include superparamagnetic iron oxide 21 22 23 , silica nanoparticles 13 24 , quantum dots 25 , gold nanoparticles 26 27 28 29 , carbon nanotubes 30 , and calcium phosphate nanoparticles 31 . However, the majority of non-viral vectors are not efficient enough to deliver genes to difficult-to-transfect hMSCs.…”

Dose-, Treatment- and Time-Dependent Toxicity of Superparamagnetic Iron Oxide Nanoparticles on Primary Rat Hepatocytes

“…Superparamagnetic iron oxide nanoparticles (SPION), which possess unique physicochemical features such as ultrafine sizes and a large surface area to mass ratio [1,2], are currently the only clinically approved metal oxide nanoparticles and the most commonly used superparamagnetic nanoparticles [2,3]. SPION have a vast variety of biomedical applications [1,4,5] including magnetic resonance imaging [6][7][8], targeted delivery of drugs [5,9] or genes [10,11], tissue engineering [12,13], hyperthermia of cancer [14,15], magnetic transfections [16,17], among others. This is despite the ban on some commercial SPION due to toxicity; ferumoxytol (Feraheme), ferumoxides, ferucarbotran, ferumoxtran-10, ferristene and ferumoxsil are SPION based magnetic resonance imaging contrast agents at current clinical trials [6][7][8].…”

Molecular Imaging of Stem Cell Transplantation for Liver Diseases: Monitoring, Clinical Translation, and Theranostics

“…The results proved that these transplanted grafts effectively restored albumin production and significantly suppressed transaminase activities in the liver damaged animal models. Meanwhile, the transplanted MSCs displayed a sensitive signal on T2/T2 ∗ -weighted MR images, which enabled in vivo tracking of the cells for up to 14 days after transplantation [62]. …”