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Polyethyleneimine-coating enhances adenoviral transduction of mesenchymal stem cells
Authors:Xinglei Yao  Na Zhou  Li Wan  Xiaodong Su  Zhao Sun  Hiroyuki Mizuguchi  Yasuo Yoshioka  Shinsaku Nakagawa  Robert Chunhua Zhao  Jian-Qing Gao
Affiliation:1. Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, 5# Dongdansantiao, 100005 Beijing, PR China;2. Institute of Pharmaceutics, Zhejiang University2, 866 Yuhangtang Road, Hangzhou 310058, PR China;3. Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 1# Shuaifuyuan, 100730 Beijing, PR China;4. Department of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan;5. Department of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan;6. Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
Abstract:Mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi-lineage potential, which makes them attractive targets for regenerative medicine applications. Efficient gene transfer into MSCs is essential for basic research in developmental biology and for therapeutic applications involving gene-modification in regenerative medicine. Adenovirus vectors (Advs) can efficiently and transiently introduce an exogenous gene into many cell types via their primary receptors, the coxsackievirus and adenovirus receptors (CARs), but not into MSCs, which lack CAR expression. To overcome this problem, an Adv coated with cationic polymer polyethyleneimine (PEI) was developed. In this study, we demonstrated that PEI coating with an optimal ratio can enhance adenoviral transduction of MSCs without cytotoxicity. We also investigated the physicochemical properties and internalization mechanisms of the PEI-coated Adv. These results could help to evaluate the potentiality of the PEI-coated Adv as a prototype vector for efficient and safe transduction into MSCs.
Keywords:Mesenchymal stem cells   Adenovirus vectors   Polyethyleneimine   Gene transduction
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