The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines.
The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines.
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DOI：
10.1038/srep17258
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发表时间：
2015-11-26
影响因子：
4.6
通讯作者：
Kunath T
中科院分区：
文献类型：
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作者：
Canham MA;Van Deusen A;Brison DR;De Sousa PA;Downie J;Devito L;Hewitt ZA;Ilic D;Kimber SJ;Moore HD;Murray H;Kunath T
人类胚胎干细胞（hESC）衍生物在再生医学中的应用正在成为现实。尽管绝大多数hESC系仅用于研究目的，但约有50个系已在良好生产规范（GMP）条件下建立。从这些指定的细胞系中分化出来的细胞类型可用于治疗黄斑变性、帕金森氏症、亨廷顿氏症、糖尿病、骨关节炎和其他退行性疾病。在进行临床试验之前，了解hESC系的遗传稳定性是至关重要的。我们采用全基因组单核苷酸多态性（SNP）阵列分析方法对25株临床级hESC细胞系的分子核型进行了评价。共检测到15个大于100 kb的唯一拷贝数变异（cnv），其中大多数是自然发生的，没有一个与培养适应有关。此外，还观察到三个大于1 Mb的拷贝中性杂合性损失（CN-LOH）区域，它们都相对较小，并且是间隙性的，表明它们不是在培养中产生的。大量具有明确分子核型的临床级hESC细胞系为再生医学临床前和临床试验的发展提供了一个坚实的起步平台。
The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality. Although the vast majority of hESC lines have been derived for research purposes only, about 50 lines have been established under Good Manufacturing Practice (GMP) conditions. Cell types differentiated from these designated lines may be used as a cell therapy to treat macular degeneration, Parkinson’s, Huntington’s, diabetes, osteoarthritis and other degenerative conditions. It is essential to know the genetic stability of the hESC lines before progressing to clinical trials. We evaluated the molecular karyotype of 25 clinical-grade hESC lines by whole-genome single nucleotide polymorphism (SNP) array analysis. A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation. In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture. The large number of available clinical-grade hESC lines with defined molecular karyotypes provides a substantial starting platform from which the development of pre-clinical and clinical trials in regenerative medicine can be realised.