Nanovector for Gene Transfection and MR Imaging of Mesenchymal Stem Cells

作者:Pang, Pengfei; Wu, Chun; Gong, Faming; Zhu, Kangshun; Meng, Xiaochun; Cheng, Du; Hu, Xiaojun; Shan, Hong*; Shuai, Xintao
来源:Journal of Biomedical Nanotechnology, 2015, 11(4): 644-656.
DOI:10.1166/jbn.2015.1967

摘要

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.