Şalva Emine, Turan Suna Özbaş, Ekentok Ceyda, Akbuğa Jülide
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Inonu University, 44280, Malatya, Turkey.
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.
Cytotechnology. 2016 Aug;68(4):1033-8. doi: 10.1007/s10616-015-9859-8. Epub 2015 Jul 2.
Establishing stable cell lines are useful tools to study the function of various genes and silence or induce the expression of a gene of interest. Nonviral gene transfer is generally preferred to generate stable cell lines in the manufacturing of recombinant proteins. In this study, we aimed to establish stable recombinant HEK-293 cell lines by transfection of chitosan complexes preparing with pDNA which contain LacZ and GFP genes. Chitosan which is a cationic polymer was used as gene delivery system. Stable HEK-293 cell lines were established by transfection of cells with complexes which were prepared with chitosan and pVitro-2 plasmid vector that contains neomycin drug resistance gene, beta gal and GFP genes. The transfection efficiency was shown with GFP expression in the cells using fluorescence microscopy. Beta gal protein expression in stable cells was examined by beta-galactosidase assay as enzymatically and X-gal staining method as histochemically. Full complexation was shown in the above of 1/1 ratio in the chitosan/pDNA complexes. The highest beta-galactosidase activity was obtained with transfection of chitosan complexes. Beta gal gene expression was 15.17 ng/ml in the stable cells generated by chitosan complexes. In addition, intensive blue color was observed depending on beta gal protein expression in the stable cell line with X-gal staining. We established a stable HEK-293 cell line that can be used for recombinant protein production or gene expression studies by transfecting the gene of interest.
建立稳定细胞系是研究各种基因功能以及沉默或诱导感兴趣基因表达的有用工具。在重组蛋白生产中,通常更倾向于使用非病毒基因转移来生成稳定细胞系。在本研究中,我们旨在通过转染含有LacZ和GFP基因的pDNA制备的壳聚糖复合物来建立稳定的重组HEK - 293细胞系。壳聚糖作为一种阳离子聚合物被用作基因传递系统。通过用壳聚糖和含有新霉素耐药基因、β - 半乳糖苷酶和GFP基因的pVitro - 2质粒载体制备的复合物转染细胞,建立了稳定的HEK - 293细胞系。使用荧光显微镜通过细胞中的GFP表达来显示转染效率。通过β - 半乳糖苷酶测定法以酶促方式和X - 半乳糖染色法以组织化学方式检测稳定细胞中β - 半乳糖苷酶蛋白的表达。壳聚糖/pDNA复合物在1/1以上的比例时显示出完全复合。壳聚糖复合物转染获得了最高的β - 半乳糖苷酶活性。壳聚糖复合物产生的稳定细胞中β - 半乳糖苷酶基因表达为15.17 ng/ml。此外,在稳定细胞系中通过X - 半乳糖染色观察到,根据β - 半乳糖苷酶蛋白表达出现强烈的蓝色。我们通过转染感兴趣的基因建立了一种可用于重组蛋白生产或基因表达研究的稳定HEK - 293细胞系。