Pekkanen-Mattila Mari, Kerkelä Erja, Tanskanen Jarno M A, Pietilä Mika, Pelto-Huikko Markku, Hyttinen Jari, Skottman Heli, Suuronen Riitta, Aalto-Setälä Katriina
REGEA, Institute for Regenerative Medicine, University of Tampere and Tampere University Hospital, Biokatu 12, Tampere, Finland.
Ann Med. 2009;41(5):360-70. doi: 10.1080/07853890802609542.
The differentiation efficiencies of human embryonic stem cell (hESC) lines differ from each other. To assess this in more detail we studied the cardiac differentiation of eight hESC lines derived in the same laboratory.
Substantial variation in growth and in the ability to form beating areas was seen between the different hESC lines; line HS346 gave the best efficiency (9.4%), while HS293 did not differentiate into beating colonies at all. Nine germ layer and differentiation markers were quantified during early differentiation in four hESC lines. The expression levels of Brachyury T, MESP1 and NKX2.5 were highest in the most efficient cardiac line (HS346). A systematic characterization of the beating cells revealed proper cardiac marker expression, electrophysiological activity, and pharmacological response.
The hESC lines derived in the same laboratory varied considerably in their potential to differentiate into beating cardiomyocytes. None of the expression markers could clearly predict cardiac differentiation potential, although the expression of early cardiomyogenic genes was upregulated in the best cardiac line. The proper cardiomyocyte characteristics and pharmacological response indicate that these cells could be used as a model for human cardiomyocytes in pharmacological and toxicological analyses when investigating new heart medications or cardiac side-effects.
人胚胎干细胞（hESC）系的分化效率各不相同。为了更详细地评估这一点，我们研究了在同一实验室获得的8个人胚胎干细胞系的心脏分化情况。
不同的人胚胎干细胞系在生长和形成跳动区域的能力方面存在显著差异；HS346系的分化效率最高（9.4%），而HS293系根本没有分化成跳动的细胞集落。在4个人胚胎干细胞系的早期分化过程中，对9种胚层和分化标志物进行了定量分析。在分化效率最高的心脏系（HS346）中，短尾相关转录因子T（Brachyury T）、中胚层后轴中胚层蛋白1（MESP1）和NK2同源盒2.5（NKX2.5）的表达水平最高。对跳动细胞的系统表征显示其具有正常的心脏标志物表达、电生理活性和药理反应。
在同一实验室获得的人胚胎干细胞系在分化为跳动心肌细胞的潜力方面差异很大。尽管在分化效率最高的心脏系中早期心肌发生基因的表达上调，但没有一种表达标志物能够明确预测心脏分化潜力。这些细胞具有正常的心肌细胞特征和药理反应，这表明在研究新型心脏药物或心脏副作用时，它们可作为人心肌细胞用于药理和毒理学分析的模型。
