上海交通大学学报（医学版）

›› 2013, Vol. 33 ›› Issue (2): 131-.doi: 10.3969/j.issn.1674-8115.2013.02.001

• 论著（基础研究） •    下一篇

新型低相对分子质量聚乙烯亚胺耦联载体(PEI-Bu)对大鼠原代骨髓间充质干细胞的基因转染效率及毒性评价

向晟楠1, 苏 靖2, 童文学1, 王传东1, 张 宁1, 戴尅戎1,3, 张晓玲1   

  1. 1.中国科学院 上海生命科学研究院/上海交通大学 医学院健康科学研究所骨科细胞与分子生物学研究组, 上海 200025； 2.上海交通大学 药学院, 上海 200240； 3.上海交通大学 医学院第九人民医院骨科, 上海 200011
  • 出版日期:2013-02-28 发布日期:2013-03-07
  • 通讯作者: 张晓玲, 电子信箱: xlzhang@sibs.ac.cn。
  • 作者简介:向晟楠（1986—）, 男, 彝族, 硕士；电子信箱: xsn20005@163.com。
  • 基金资助:

    国家科技部国际合作项目(2011DFA30790)；上海市教委曙光计划（10SG22）；上海市教委重点学科建设基金（J50206）；上海交通大学医工合作基金(YG2010MS48)

Toxicity and transfection efficiency of novel low molecular weight polyethylenimine conjugates (PEI-Bu) on rat primary mesenchymal stem cells

XIANG Sheng-nan1, SU Jing2, TONG Wen-xue1, WANG Chuan-dong1, ZHANG Ning1, DAI Ke-rong1,3, ZHANG Xiao-ling1   

  1. 1.Laboratory of Orthopedic Cellular and Molecular Biology, Institute of Health Sciences, Shanghai Jiaotong University School of Medicine &|Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China；2.School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China； 3.Department of Orthopaedics, the Ninth People´s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
  • Online:2013-02-28 Published:2013-03-07
  • Supported by:

    Foundation of the Ministry of Science and Technology of China, 2011DFA30790； Shanghai Education Committee Foundation, 10SG22, J50206； Shanghai Jiaotong University Foundation, YG2010MS48

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摘要：

目的 构建新型低相对分子质量聚乙烯亚胺(PEI)耦联载体，评估其对原代大鼠骨髓间充质干细胞（BMSCs）的细胞毒性及转染效率。方法 利用可降解的氨基甲酸酯化学键耦联相对分子质量为800的PEI 制备低相对分子质量的PEI （PEI 800）衍生物纳米非病毒载体，命名为PEI-Bu；进一步对PEI-Bu压缩DNA的能力、体外降解效率及对原代BMSCs的细胞毒性和基因转染效率进行生物学评价。结果 PEI-Bu能有效压缩质粒DNA并形成稳定的复合物，所形成的复合物粒径约50 nm。与实验室常用的已商品化的相对分子质量为25 000 的PEI （PEI 25 000）相比，PEI-Bu对大鼠原代BMSCs的细胞毒性较小，且基因转染效率更高。结论 作为一种新型的非病毒纳米载体，PEI-Bu能有效转染BMSCs，且安全性较高，具有进一步研发的价值。

关键词: 非病毒纳米载体, 聚乙烯亚胺, 骨髓间充质干细胞, 基因转染效率

Abstract:

Objective To construct the novel low molecular weight polyethylenimine (PEI) conjugates, and evaluate its toxicity and transfection efficiency on rat bone marrow mesenchymal stem cells (BMSCs). Methods Low molecular weight PEI derivative non-viral nano vector was developed by conjugation of PEI of 800 in molecular weight and degradable carbamate linkage, and was named as PEI-Bu. The DNA condensation capability, in vitro degradation efficiency as well as toxicity and transfection efficiency on primary BMSCs of PEI-Bu were investigated. Results PEI-Bu efficiently condensed plasmid DNA, and stable polyplexes were formed, with the size of polyplexes being about 50 nm. Compared with commercialized PEI 25 000 (PEI of 25 000 in molecular weight) commonly used in laboratories, PEI-Bu had lower toxicity and higher transfection efficiency on rat primary BMSCs. Conclusion As a novel non-viral nano vector, PEI-Bu can efficiently transfect BMSCs with favorable safety, which has a potential value for further development.

Key words: non-viral nano vector, polyethylenimine, bone marrow mesenchymal stem cells, gene transfection efficiency