Lifelong reporter gene imaging in the lungs of mice following polyethyleneimine-mediated sleeping-beauty transposon delivery
Lifelong reporter gene imaging in the lungs of mice following polyethyleneimine-mediated sleeping-beauty transposon delivery
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DOI：
10.1016/j.biomaterials.2010.11.026
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发表时间：
2011-03-01
期刊：
影响因子：
14
通讯作者：
Deng, Win-Ping
中科院分区：
文献类型：
--
作者：
Lin, Erh-Hsuan;Keramidas, Michelle;Deng, Win-Ping
聚乙烯亚胺（PEI）是一种在体内有效传递基因的阳离子聚合物。含有睡美人转座子的质粒DNA在pei介导的递送后可在小鼠肺中诱导长期的转基因表达。在本报告中，我们使用无创生物发光成像（BLI）技术跟踪PEI/SB在小鼠肺中传递介导的报告基因表达。分娩后，报告基因信号在前两周内迅速衰减到几乎检测不到的水平，但在随后的几周内信号逐渐增强，最终达到稳定的水平，并一直保持到动物自然死亡。转基因表达的稳定与少量PEI/ sb标记的肺泡细胞的增殖有关，这些细胞在正常条件下和对急性局部损伤的反应中增殖，以修复上皮，并可能在肺泡的长期稳态维持中发挥作用。本文提供的数据表明，PEI/SB的全身递送特异性地诱导了一小群肺泡祖细胞的稳定转染。该技术为未来远端肺生物学和组织再生治疗的研究提供了一个有希望的平台。(C) 2010 Elsevier Ltd.版权所有。
Polyethyleneimine (PEI) is a cationic polymer that is effective in gene delivery in vivo. Plasmid DNA incorporating the Sleeping-Beauty (SB) transposon has been shown to induce long-term transgene expression in mouse lungs after PEI-mediated delivery. In the current report, we followed the reporter gene expression mediated by PEI/SB delivery in lungs of mice using the non-invasive bioluminescent imaging (BLI) technology. After delivery, the reporter gene signal showed a rapid decay in the first two weeks to a nearly undetectable level, but then the signal augmented gradually in the following weeks and finally reached a stable level that maintained until the natural death of animals. The stabilization of transgene expression is associated with the multiplication of a small number of PEI/SB-labeled alveolar cells, which proliferated both under normal conditions and in response to acute local injury for epithelia repair, and may play a role in long-term homeostatic maintenance in alveoli. The data presented here suggests that systemic delivery of PEI/SB induces stable transfection specifically in a small population of alveolar progenitor cells. The technique provides a promising platform for future research in distal lung biology and tissue regenerative therapy. (C) 2010 Elsevier Ltd. All rights reserved.