Mesenchymal Stem Cells as a Novel Carrier for Targeted Delivery of Gene in Cancer Therapy Based on Nonviral Transfection

Abstract

The success of gene therapy relies largely on an effective targeted gene delivery system. Till recently, more and more targeted delivery carriers, such as liposome, nanoparticles, microbubbles, etc., have been developed. However, the clinical applications of these systems were limited for their several disadvantages. Therefore, design and development of novel drug/gene delivery vehicles became a hot topic. Cell-based delivery systems are emerging as an alternative for the targeted delivery system as we described previously. Mesenchymal stem cells (MSCs) are an attractive cell therapy carrier for the delivery of therapeutic agents into tumor sites mainly for their tumor-targeting capacities. In the present study, a nonviral vector, PEI(600)-Cyd, prepared by linking low molecular weight polyethylenimine (PEI) and β-cyclodextrin (β-CD), was used to introduce the therapeutical gene, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), to MSCs. Meanwhile, the characterization, transfection efficiency, cytotoxicity, cellular internalization, and its mechanism of this nonviral vector were evaluated. The in vitro expression of TRAIL from MSCs-TRAIL was demonstrated by both enzyme-linked immunosorbent assay and Western blot analysis. The lung tumor homing ability of MSCs was further confirmed by the in vitro and in vivo model. Moreover, the therapeutic effects as well as the safety of MSCs-TRAIL on lung metastases bearing C57BL/6 mice and normal C57BL/6 mice were also demonstrated. Our results supported both the effectiveness of nonviral vectors in transferring the therapeutic gene to MSCs and the feasibility of using MSCs as a targeted gene delivery carrier, indicating that MSCs could be a promising tumor target delivery vehicle in cancer gene therapy based on nonviral gene recombination.

Complexation of Apoptotic Genes with Polyethyleneimine (PEI)-Coated Poly-(DL)-Lactic-Co-Glycolic Acid Nanoparticles for Cancer Cell Apoptosis

“…40 41 Gene delivery systems have recently received great attention in cancer therapy due to their promising application routes by using suitable non-toxic delivery vehicles. [42][43][44] To achieve successful gene therapy, several types of gene delivering carriers consisting of both organic and inorganic materials have been developed. 45 46 Among these, nanoparticles have been recently studied as suitable carriers for gene delivery, 47-49 because they demonstrate potential capabilities of delivering specific genes through their excellent uptake via endocytosis.…”

Human Mesenchymal Stem Cells Promote Cancer Motility and Cytokine Secretion in vitro

“…Furthermore, nanoparticles would be separated by the reticuloendothelial system [Li et al, 2011]. The liposomes are rapidly recognized as well and cleared by the reticuloendothelial system from the circulating blood [Hu et al, 2012]. Therefore, a potential solution may be to use mesenchymal stem cells.…”

Direct Head-To-Head Comparison of Cationic Liposome-Mediated Gene Delivery to Mesenchymal Stem/Stromal Cells of Different Human Sources: A Comprehensive Study

“…Despite being a very appealing and promising field, one major barrier to the success of the genetic engineering of MSC is still the lack of a safe and efficient method of gene delivery (Reiser et al, 2005;Santos et al, 2011;Hu et al, 2012). Viral-based vectors, namely retrovirus and adenovirus, are currently the most commonly used system to deliver genes in clinical trials (Edelstein et al, 2007;Park et al, 2012), as they offer a robust and sustained high gene delivery efficiency and expression.…”