title: Gene recombinant bone marrow mesenchymal stem cells as a tumor-targeted suicide gene delivery vehicle in pulmonary metastasis therapy using non-viral transfection.
abstract: One of the main limitations of anti-tumor gene therapy is the lack of an effective way to deliver therapeutic genes to tumor sites. Bone marrow mesenchymal stem cells (BMSCs) have been proposed as cellular delivery vehicles to tumor sites in tumor-targeted cancer gene therapy. Here, we investigated the therapeutic effects of cytomegalovirus-thymidine kinase expressing BMSCs (TK-BMSCs) on pulmonary melanoma metastasis combined with prodrug ganciclovir. BMSCs were successfully engineered through a non-viral gene vector. The gene recombinant BMSCs migrated to the pulmonary area and were found to have the tendency to target tumor nodules after systemic delivery. In vitro results demonstrate that the engineered BMSCs have significant suicide effects in the presence of ganciclovir in a dose-dependent manner and can exert a sufficient bystander effect on B16F10 tumor cells in co-culture experiments. In vivo studies confirmed the therapeutic effects of TK-BMSCs/ganciclovir on the metastasis tumor model.
  
  
  BACKGROUND
  This study investigates the possibility of gene transfer via bone marrow mesenchymal stem cells in anti-cancer gene therapy using a metastatic melanoma model and cytomegalovirus-thymidine kinase expressing stem cells, demonstrating clear therapeutic effects.
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China.
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Zhang
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China.
authors.forename: Zhong-Yue
authors.initials: ZY
authors.lastname: Yuan
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China. Electronic address: hu_yulan@hotmail.com.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Hu
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China. Electronic address: gaojianqing@zju.edu.cn.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D045744:Cell Line, Tumor; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003587:Cytomegalovirus / Q000235:genetics; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D059630:Mesenchymal Stem Cells; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D013937:Thymidine Kinase
keywords: BMSCs; CMV-TK/GCV; Non-viral gene vector; Pulmonary melanoma metastasis; Suicide gene therapy