期刊
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
卷 55, 期 -, 页码 53-62出版社
WILEY-BLACKWELL
DOI: 10.1042/BA20090210
关键词
gene therapy; lentivirus; mesenchymal stem cell (MSC); transduction; umbilical cord
资金
- National Natural Science Foundation of China [30471983, 30840053]
- Jiangsu Province's Outstanding Medical Academic Leader Program [LJ200614]
- Natural Science Foundation of the Jiangsu Province [BK2007705, BK2007092, BK2008232]
- Sci-Tech Innovation Team and Talents of Jiangsu University [2008-018-02]
- Scientific Research Foundation of Jiangsu University [07JDG056, 04CX07]
- Foundation of the Jiangsu Province [BA2009124]
Gene delivery into MSCs (mesenchymal stem cells) has great promise for gene therapy, and lentiviral transduction has recently been shown to be a highly efficient method for gene delivery. Our previous studies indicated that the umbilical cord is a new source of MSCs; however, it was unclear whether the UC-MSCs (umbilical-cord-derived MSCs) would retain their characteristics after LV (lentivirus)-mediated gene transduction. The aim of the present study is to investigate the feasibility of transducing UC-MSCs with lentiviral vectors and to determine whether these transduced stem cells would retain their ability to differentiate into different lineages. Herein, we demonstrate that the percentage of EGFP (enhanced green fluorescent protein)-positive cells increased with the MOI (multiplicity of infection) and the number of transduction cycles. In addition, we observed that the transduced MSCs were capable of differentiating into adipogenic and osteogenic lineages expressing lineage-specific genes while maintaining high EGFP expression levels. In their undifferentiated state, the UC-MSCs continued to express both the transgene [EGFP or TNF (tumour necrosis factor)-Tumstatin] and stem cell markers such as Oct-4, Nanog, BMI-1 and nucleostemin. The presence of exogenous antitumour molecule-coding gene integration was verified by PCR and RT-PCR (reverse transcription-PCR) and also by immunohistochemistry. It was also shown that TNF-Tumstatin that can be secreted by MSCs has a cytotoxic effect on prostate cancer cells in vitro. These findings suggest that lentiviral transduction may be used to deliver therapeutic genes to human UC-MSCs and this may have a wide range of applications in gene therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据