Abstract
The neural ganglioside GD2 has recently been reported to be a novel surface marker that is only expressed on human bone marrow mesenchymal stem cells within normal marrow. In this study, an MRI-visible, targeted, non-viral vector for effective gene delivery to human bone marrow mesenchymal stem cells was first synthesized by attaching a targeting ligand, the GD2 single chain antibody (scAbGD2), to the distal ends of PEG-g-PEI-SPION. The targeted vector was then used to condense plasmid DNA to form nanoparticles showing stable small size, low cytotoxicity, and good biocompatibility. Based on a reporter gene assay, the transfection efficiency of targeting complex reached the highest value at 59.6% ± 4.5% in human bone marrow mesenchymal stem cells, which was higher than those obtained using nontargeting complex and lipofectamine/pDNA (17.7% ± 2.9% and 34.9% ± 3.6%, respectively) (P<0.01). Consequently, compared with the nontargeting group, more in vivo gene expression was observed in the fibrotic rat livers of the targeting group. Furthermore, the targeting capacity of scAbGD2-PEG-g-PEI-SPION was successfully verified in vitro by confocal laser scanning microscopy, Prussian blue staining, and magnetic resonance imaging. Our results indicate that scAbGD2-PEG-g-PEI-SPION is a promising MRI-visible non-viral vector for targeted gene delivery to human bone marrow mesenchymal stem cells.
Highlights
Human mesenchymal stem cells have the capability for self-renewal and differentiation into a broad spectrum of mesenchymal tissues, such as bone, fat, and cartilage [1,2,3]
We prove that scAbGD2PEG-g-PEI-superparamagnetic iron oxide nanoparticles (SPION) is an efficient MRI-visible non-viral vector for targeted gene delivery to human bone marrow mesenchymal stem cells (hBMSCs) in vitro and in vivo
The purified plasmid DNAs (pDNAs) were resuspended in deionized water and kept in aliquots at a concentration of 2.4 μg/μL. hBMSCs isolation for research was approved by the institutional review board of the third affiliated hospital of Sun Yat-Sen University according to a protocol previously described [23]
Summary
Human mesenchymal stem cells (hMSCs) have the capability for self-renewal and differentiation into a broad spectrum of mesenchymal tissues, such as bone, fat, and cartilage [1,2,3]. Human bone marrow mesenchymal stem cells (hBMSCs) have been widely studied because they are considerably more abundant and easier to obtain compared with hMSCs existing in the stroma of other tissues [4,5]. The neural ganglioside GD2 has been reported to be a novel surface marker that is only expressed on hBMSCs within normal marrow [9]. HMSCs derived from umbilical cord were reported to be the only cells that expressed this marker within umbilical cord at earlypassages [10]
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