BMP2 gene delivery to bone mesenchymal stem cell by chitosan-g-PEI nonviral vector

被引:28
作者
Yue, Jianhui [1 ,4 ]
Wu, Jun [2 ]
Liu, Di [1 ,3 ]
Zhao, Xiaoli [1 ,4 ]
Lu, William W. [2 ]
机构
[1] Chinese Acad Sci, Shenzhen Inst Adv Technol, Inst Biomed & Biotechnol, Ctr Human Tissues & Organs Degenerat, Shenzhen 518055, Peoples R China
[2] Univ Hong Kong, Dept Orthopaed & Traumatol, Pokfulam 999077, Hong Kong, Peoples R China
[3] Harbin Med Univ, Dept Pharmacol, Harbin 150081, Peoples R China
[4] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Marine Biomed Mat, Shenzhen 518055, Peoples R China
来源
NANOSCALE RESEARCH LETTERS | 2015年 / 10卷
基金
中国国家自然科学基金;
关键词
Chitosan; Polyethylenimine; Stem cell; Osteogenic differentiation; Gene delivery; MOLECULAR-WEIGHT POLYETHYLENIMINE; MORPHOGENETIC PROTEIN-2; GRAFT-POLYETHYLENIMINE; GROWTH-FACTOR; IN-VITRO; REGENERATION; THERAPY; NANOPARTICLES; SIRNA; DNA;
D O I
10.1186/s11671-015-0906-3
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Nanotechnology has made a significant impact on the development of nanomedicine. Nonviral vectors have been attracting more attention for the advantage of biosafety in gene delivery. Polyethylenimine (PEI)-conjugated chitosan (chitosan-g-PEI) emerged as a promising nonviral vector and has been demonstrated in many tumor cells. However, there is a lack of study focused on the behavior of this vector in stem cells which hold great potential in regenerative medicine. Therefore, in this study, in vitro gene delivering effect of chitosan-g-PEI was investigated in bone marrow stem cells. pIRES2-ZsGreen1-hBMP2 dual expression plasmid containing both the ZsGreen1 GFP reporter gene and the BMP2 functional gene was constructed for monitoring the transgene expression level. Chitosan-g-PEI-mediated gene transfer showed 17.2% of transfection efficiency and more than 80% of cell viability in stem cells. These values were higher than that of PEI. The expression of the delivered BMP2 gene in stem cells enhanced the osteogenic differentiation. These results demonstrated that chitosan-g-PEI is capable of applying in delivering gene to stem cells and providing potential applications in stem cell-based gene therapy.
引用
收藏
页数:11
相关论文
共 54 条
[1]   A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: Polyethylenimine [J].
Abdallah, B ;
Hassan, A ;
Benoist, C ;
Goula, D ;
Behr, JP ;
Demeneix, BA .
HUMAN GENE THERAPY, 1996, 7 (16) :1947-1954
[2]   Nucleofection-based ex vivo nonviral gene delivery to human stem cells as a platform for tissue regeneration [J].
Aslan, Hadi ;
Zilberman, Yoram ;
Arbeli, Vered ;
Sheyn, Dima ;
Matan, Yoav ;
Liebergall, Meir ;
Li, Jin Zhong ;
Helm, Gregory A. ;
Gazit, Dan ;
Gazit, Zulma .
TISSUE ENGINEERING, 2006, 12 (04) :877-889
[3]   Gene therapy approaches to regenerating bone [J].
Bleich, Nadav Kimelman ;
Kallai, Ilan ;
Lieberman, Jay R. ;
Schwarz, Edward M. ;
Pelled, Gadi ;
Gazit, Dan .
ADVANCED DRUG DELIVERY REVIEWS, 2012, 64 (12) :1320-1330
[4]   Gene therapy for new bone formation using adeno-associated viral bone morphogenetic protein-2 vectors [J].
Chen, Y ;
Luk, KDK ;
Cheung, KMC ;
Xu, R ;
Lin, MC ;
Lu, WW ;
Leong, JCY ;
Kung, HF .
GENE THERAPY, 2003, 10 (16) :1345-1353
[5]   Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions [J].
Elsabahy, Mahmoud ;
Nazarali, Adil ;
Foldvari, Marianna .
CURRENT DRUG DELIVERY, 2011, 8 (03) :235-244
[6]   Progress and Prospects: genetic treatments for disorders of bones and joints [J].
Evans, C. H. ;
Ghivizzani, S. C. ;
Robbins, P. D. .
GENE THERAPY, 2009, 16 (08) :944-952
[7]   Gene therapy for the regeneration of bone [J].
Evans, Christopher .
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED, 2011, 42 (06) :599-604
[8]   Gene therapy platform for bone regeneration using an exogenously regulated, AAV-2-based gene expression system [J].
Gafni, Y ;
Pelled, G ;
Zilberman, Y ;
Turgeman, G ;
Apparailly, F ;
Yotvat, H ;
Galun, E ;
Gazit, Z ;
Jorgensen, C ;
Gazit, D .
MOLECULAR THERAPY, 2004, 9 (04) :587-595
[9]   Gene-carried chitosan-linked-PEI induced high gene transfection efficiency with low toxicity and significant tumor-suppressive activity [J].
Gao, Jian-Qing ;
Zhao, Qing-Qing ;
Lv, Teng-Fei ;
Shuai, Wu-Ping ;
Zhou, Jun ;
Tang, Gu-Ping ;
Liang, Wen-Quan ;
Tabata, Yasuhiko ;
Hu, Yu-Lan .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2010, 387 (1-2) :286-294
[10]   Gene therapy clinical trials worldwide to 2012 an update [J].
Ginn, Samantha L. ;
Alexander, Ian E. ;
Edelstein, Michael L. ;
Abedi, Mohammad R. ;
Wixon, Jo .
JOURNAL OF GENE MEDICINE, 2013, 15 (02) :65-77