Gordeeva O F, Mitalipov Sh M
Ontogenez. 2008 Nov-Dec;39(6):405-19.
Permanent lines of pluripotent stem cells can be obtained from humans and monkeys using different techniques and from different sources--inner cell mass of the blastocyst, primary germ cells, parthenogenetic oocytes, and mature spermatogonia--as well as by transgenic modification of various adult somatic cells. Despite different origin, all pluripotent lines demonstrate considerable similarity of the major biological properties: active self-renewal and differentiation into various somatic and germ cells in vitro and in vivo, similar gene expression profiles, and similar cell cycle structure. Ten years of intense studies on the stability of different human and monkey embryonic stem cells demonstrated that, irrespective of their origin, long-term in vitro cultures lead to the accumulation of chromosomal and gene mutations as well as epigenetic changes that can cause oncogenic transformation of cells. This review summarizes the research data on the genetic and epigenetic stability of different lines of pluripotent stem cells after long-term in vitro culture. These data were used to analyze possible factors of the genome and epigenome instability in pluripotent lines. The prospects of using pluripotent stem cells of different origin in cell therapy and pharmacological studies were considered.
利用不同技术并从不同来源(囊胚的内细胞团、原始生殖细胞、孤雌生殖卵母细胞和成熟精原细胞),以及通过对各种成人体细胞进行转基因修饰,可从人类和猴子身上获得多能干细胞的永久细胞系。尽管来源不同,但所有多能细胞系在主要生物学特性上都表现出相当大的相似性:在体外和体内具有活跃的自我更新能力,并能分化为各种体细胞和生殖细胞,具有相似的基因表达谱以及相似的细胞周期结构。对不同人类和猴子胚胎干细胞稳定性进行的十年深入研究表明,无论其来源如何,长期体外培养都会导致染色体和基因突变的积累以及表观遗传变化,进而可能导致细胞发生致癌转化。本综述总结了长期体外培养后不同多能干细胞系遗传和表观遗传稳定性的研究数据。这些数据用于分析多能细胞系中基因组和表观基因组不稳定的可能因素。文中还探讨了使用不同来源的多能干细胞进行细胞治疗和药理研究的前景。