title: Design of magnetic gene complexes as effective and serum resistant gene delivery systems for mesenchymal stem cells.
abstract: Gene engineered mesenchymal stem cells (MSCs) have been proposed as promising tools for their various applications in biomedicine. Nevertheless, the lack of an effective and safe way to genetically modify these stem cells is still a major obstacle in the current studies. Herein, we designed novel magnetic complexes by assembling cationized pullulan derivatives with magnetic iron oxide nanoparticles for delivering target genes to MSCs. Results showed that this complexes achieved effective gene expression with the assistance of external magnetic field, and resisted the adverse effect induced by serum proteins on the gene delivery. Moreover, neither significant cytotoxicity nor the interference on the osteogenic differentiation to MSCs were observed after magnetofection. Further studies revealed that this effective and serum resistant gene transfection was partly due to the accelerated and enhanced intracellular uptake process driven by external magnetic field. To conclude, the current study presented a novel option for genetic modification of MSCs in an effective, relatively safe and serum compatible way.
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Zhang
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Jia-He
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Qian-Hao
authors.initials: QH
authors.lastname: Xu
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Xia-Rong
authors.initials: XR
authors.lastname: Wang
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Jingxiong
authors.initials: J
authors.lastname: Lu
authors.affiliation: Zhejiang Pharmaceutical College, Ningbo, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Jun-Ichiro
authors.initials: JI
authors.lastname: Jo
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Daishun
authors.initials: D
authors.lastname: Ling
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. Electronic address: yasuhiko@frontier.kyoto-u.ac.jp.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China. Electronic address: gaojianqing@zju.edu.cn.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000009:adverse effects*; D002470:Cell Survival; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D005936:Glucans / Q000737:chemistry*; D008280:Magnetics; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010012:Osteogenesis; D051381:Rats; D014162:Transfection / Q000379:methods*
chemical_list: D001798:Blood Proteins; D005936:Glucans; D058185:Magnetite Nanoparticles; C009109:pullulan
keywords: Iron oxide nanoparticles; Magnetofection; Mesenchymal stem cells; Pullulan; Serum resistant