Gaztelumendi Nerea, Nogués Carme
Universitat Autònoma de Barcelona (UAB). Bellaterra, Catalonia, Spain.
Sci Rep. 2014 Jun 17;4:5324. doi: 10.1038/srep05324.
Embryonic Stem Cells (ESCs) are expected to show a stable euploid karyotype, but in the last decade (sub)chromosomal aberrations have been systematically described in these cell lines when maintained in vitro. Culture conditions and long-term culture have been traditionally proposed as possible factors involved in the acquisition of chromosomal abnormalities. Thus, we analyzed the chromosome constitution, the undifferentiated state and the functional pluripotency of three different mouse ESCs grown under the same culture conditions. Two cell lines were unstable from early passages, whereas the third one retained its chromosome integrity after long-term culture despite using enzymatic methods for cell disaggregation. Trisomy 8 and 11 were clonally selected in both unstable cell lines, which also showed a higher growth rate than our normal cell line and suffered morphological changes in colony shape with increasing passage number. Regardless of the length of culture or the chromosome instability, all cell lines preserved their differentiation potential. These results confirm that double trisomy 8 and 11 confers a growth advantage to the abnormal cells, but not at the expense of cell differentiation. The presence of chromosome instability, widely related to tumor development and cancer disease, highlights the risk of using pluripotent cells in regenerative medicine.
胚胎干细胞（ESCs）预期会呈现稳定的整倍体核型，但在过去十年中，当这些细胞系在体外培养维持时，（亚）染色体畸变已被系统地描述出来了。传统上认为培养条件和长期培养可能是导致染色体异常出现的因素。因此，我们分析了在相同培养条件下生长的三种不同小鼠胚胎干细胞的染色体构成、未分化状态和功能多能性。两个细胞系从早期传代时就不稳定，而第三个细胞系尽管使用酶法进行细胞解离，但经过长期培养后仍保持其染色体完整性。在两个不稳定细胞系中均克隆选择出了8号和11号染色体三体性，这两个细胞系的生长速度也比我们正常细胞系更快，并且随着传代次数增加，集落形状出现形态学变化。无论培养时间长短或染色体是否不稳定，所有细胞系都保留了它们的分化潜能这些结果证实，8号和11号染色体双三体赋予了异常细胞生长优势，但并非以牺牲细胞分化为代价。染色体不稳定的存在与肿瘤发生和癌症疾病密切相关，这凸显了在再生医学中使用多能细胞的风险。
