title: 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.
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Hu
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Zhang
authors.forename: Pei-Hong
authors.initials: PH
authors.lastname: Miao
authors.forename: Gu-Ping
authors.initials: GP
authors.lastname: Tang
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000378:metabolism
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; D047392:beta-Cyclodextrins; D011094:Polyethyleneimine