Molla Kazemiha Vahid, Bonakdar Shahin, Amanzadeh Amir, Azari Shahram, Memarnejadian Arash, Shahbazi Shirin, Shokrgozar Mohammad Ali, Mahdian Reza
National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Cytotechnology. 2016 Aug;68(4):1063-80. doi: 10.1007/s10616-015-9862-0. Epub 2015 Mar 6.
Mycoplasmas are the most important contaminants of cell cultures throughout the world. They are considered as a major problem in biological studies and biopharmaceutical economic issues. In this study, our aim was to find the best standard technique as a rapid method with high sensitivity, specificity and accuracy for the detection of mycoplasma contamination in the cell lines of the National Cell Bank of Iran. Thirty cell lines suspected to mycoplasma contamination were evaluated by five different techniques including microbial culture, indirect DNA DAPI staining, enzymatic mycoalert(®) assay, conventional PCR and real-time PCR. Five mycoplasma-contaminated cell lines were assigned as positive controls and five mycoplasma-free cell lines as negative controls. The enzymatic method was performed using the mycoalert(®) mycoplasma detection kit. Real-time PCR technique was conducted by PromoKine diagnostic kits. In the conventional PCR method, mycoplasma genus-specific primers were designed to analyze the sequences based on a fixed and common region on 16S ribosomal RNA with PCR product size of 425 bp. Mycoplasma contamination was observed in 60, 56.66, 53.33, 46.66 and 33.33 % of 30 different cell cultures by real-time PCR, PCR, enzymatic mycoalert(®), indirect DNA DAPI staining and microbial culture methods, respectively. The analysis of the results of the different methods showed that the real-time PCR assay was superior the other methods with the sensitivity, specificity, accuracy, predictive value of positive and negative results of 100 %. These values were 94.44, 100, 96.77, 100 and 92.85 % for the conventional PCR method, respectively. Therefore, this study showed that real-time PCR and PCR assays based on the common sequences in the 16S ribosomal RNA are reliable methods with high sensitivity, specificity and accuracy for detection of mycoplasma contamination in cell cultures and other biological products.
支原体是全球细胞培养中最重要的污染物。它们被视为生物学研究和生物制药经济问题中的一个主要难题。在本研究中,我们的目标是找到一种最佳标准技术,作为一种具有高灵敏度、特异性和准确性的快速方法,用于检测伊朗国家细胞库细胞系中的支原体污染。通过包括微生物培养、间接DNA DAPI染色、酶促Mycoalert(®)检测、常规PCR和实时PCR在内的五种不同技术,对30株疑似支原体污染的细胞系进行了评估。将五株受支原体污染的细胞系指定为阳性对照,五株无支原体污染的细胞系作为阴性对照。酶促方法使用Mycoalert(®)支原体检测试剂盒进行。实时PCR技术通过PromoKine诊断试剂盒进行。在常规PCR方法中,设计了支原体属特异性引物,用于基于16S核糖体RNA上的固定且常见区域分析序列,PCR产物大小为425 bp。通过实时PCR、PCR、酶促Mycoalert(®)、间接DNA DAPI染色和微生物培养方法,在30种不同细胞培养物中分别观察到支原体污染的比例为60%、56.66%、53.33%、46.66%和33.33%。对不同方法结果的分析表明,实时PCR检测在灵敏度、特异性、准确性、阳性和阴性结果的预测值方面均为100%,优于其他方法。常规PCR方法的这些值分别为94.44%、100%、96.77%、100%和92.85%。因此,本研究表明,基于16S核糖体RNA中常见序列的实时PCR和PCR检测是检测细胞培养物和其他生物制品中支原体污染的可靠方法,具有高灵敏度、特异性和准确性。