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首页> 外文期刊>In Vitro Cellular and Developmental Biology. Animal: Journal of the Tissues Culture Association >Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7, and hTERT genes
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Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7, and hTERT genes

机译：人乳头瘤病毒E6，E7和hTERT基因永生化的人间充质干细胞的染色体不稳定

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Human mesenchymal stem cells (hMSCs) are expected to be an enormous potential source for future cell therapy, because of their self-renewing divisions and also because of their multiple-lineage differentiation. The finite lifespan of these cells, however, is a hurdle for clinical application. Recently, several hMSC lines have been established by immortalized human telomerase reverse transcriptase gene (hTERT) alone or with hTERT in combination with human papillomavirus type 16 E6/E7 genes (E6/E7) and human proto-oncogene, Bmi-1, but have not so much been characterized their karyotypic stability in detail during extended lifespan under in vitro conditions. In this report, the cells immortalized with the hTERT gene alone exhibited little change in karyotype, whereas the cells immortalized with E6/E7 plus hTERT genes or Bmi-1, E6 plus hTERT genes were unstable regarding chromosome numbers, which altered markedly during prolonged culture. Interestingly, one unique chromosomal alteration was the preferential loss of chromosome 13 in three cell lines, observed by fluorescence in situ hybridization (FISH) and comparative-genomic hybridization (CGH) analysis. The four cell lines all maintained the ability to differentiate into both osteogenic and adipogenic lineages, and two cell lines underwent neuroblastic differentiation. Thus, our results were able to provide a step forward toward fulfilling the need for a sufficient number of cells for new therapeutic applications, and substantiate that these cell lines are a useful model for understanding the mechanisms of chromosomal instability and differentiation of hMSCs.
机译：人间充质干细胞（hMSCs）有望因自身的自我更新分裂以及多系分化而成为未来细胞治疗的巨大潜力。然而，这些细胞的有限寿命是临床应用的障碍。最近，已通过永生化的人类端粒酶逆转录酶基因（hTERT）单独或与hTERT结合人类乳头瘤病毒16型E6 / E7型基因（E6 / E7）和人类原癌基因Bmi-1建立了几种hMSC系，但它们具有在体外条件下延长寿命期间，并没有详细描述它们的核型稳定性。在此报告中，仅用hTERT基因永生的细胞的核型几乎没有变化，而用E6 / E7 + hTERT基因或Bmi-1，E6 + hTERT基因永生的细胞的染色体数目不稳定，在长期培养过程中显着改变。有趣的是，一种独特的染色体改变是通过荧光原位杂交（FISH）和比较基因组杂交（CGH）分析观察到的三种细胞系中13号染色体的优先丢失。这四个细胞系均保持分化为成骨和成脂谱系的能力，并且两个细胞系经历了神经母细胞分化。因此，我们的结果能够为满足用于新的治疗应用的足够数量的细胞的需求提供一个前进的方向，并证实这些细胞系是了解染色体不稳定性和hMSCs分化机制的有用模型。

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