Comparison of cardiomyogenic potential among human ESC and iPSC lines.
Comparison of cardiomyogenic potential among human ESC and iPSC lines.
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DOI：
10.3727/096368912x653165
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发表时间：
2012
影响因子：
3.3
通讯作者：
Lough JW
中科院分区：
文献类型：
--
作者：
Sepac A;Si-Tayeb K;Sedlic F;Barrett S;Canfield S;Duncan SA;Bosnjak ZJ;Lough JW
我们最近报道了用激活素- a和Bmp4在确定的培养基中诱导多能H1人胚胎干细胞（hESCs）团5天后，在3-4周内发生了节律性收缩心肌细胞的广泛分化。在这项研究中，同样的方法被用于评估人类诱导多能细胞（hipsc）是否可以类似地经历心肌细胞分化，hipsc理论上可能为移植治疗提供患者匹配细胞的无限来源。通过监测四种多能细胞系——H1和H9 hESCs以及C2a和C6a hiPSCs的节律性收缩、形态分化和心肌生成基因的表达，平行比较了它们的分化情况。通过表达心肌系标记物MESP1、ISL1和NKX2-5，将四种细胞系诱导为心肌系。然而，与H9，尤其是H1 hESCs中广泛出现的条纹和节律性收缩相反，两种hiPSC系都表现出较差的终末分化。这些发现表明，生成hipsc的精细模式，以及诱导它们的心肌生成，可能需要实现它们作为心脏再生介质的潜力。
We recently reported that following induction of clumps of pluripotent H1 human embryonic stem cells (hESCs) with activin-A and Bmp4 in defined medium for five days, widespread differentiation of rhythmically contracting cardiomyocytes occurs within 3–4 weeks. In this study the same approach was used to assess whether human induced pluripotent cells (hiPSCs), which may theoretically provide an unlimited source of patient-matched cells for transplantation therapy, can similarly undergo cardiomyocyte differentiation. Differentiation of four pluripotent cell-lines – H1 and H9 hESCs, and C2a and C6a hiPSCs – was compared in parallel by monitoring rhythmic contraction, morphologic differentiation, and expression of cardiomyogenic genes. Based on expression of the cardiomyogenic lineage markers MESP1, ISL1 and NKX2-5, all four cell-lines were induced into the cardiomyogenic lineage. However, in contrast to the widespread appearance of striations and rhythmic contractility seen in H9 and especially in H1 hESCs, both hiPSC lines exhibited poor terminal differentiation. These findings suggest that refined modes of generating hiPSCs, as well as of inducing cardiomyogenesis in them, may be required to fulfill their potential as agents of cardiac regeneration.