Cardiac myocyte force development during differentiation and maturation.

Cardiac myocyte force development during differentiation and maturation.
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DOI:
10.1111/j.1749-6632.2009.05091.x
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发表时间:
2010-02
影响因子:
5.2
通讯作者:
McCulloch AD
McCulloch AD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jacot JG;Kita-Matsuo H;Wei KA;Chen HS;Omens JH;Mercola M;McCulloch AD

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产前时期心肌细胞的成熟与细胞外基质机械特性的变化同时发生。我们研究了细胞外硬度对在胶原涂层凝胶上生长的新生大鼠心室肌细胞的心肌细胞成熟的影响。 10 kPa 基底上的细胞发育出对齐的肌节,而较硬基底上的细胞则具有未对齐的肌节和应力纤维。与在较硬或较软的基质上相比,细胞在硬度与天然心肌相似的凝胶上产生更大的机械力。为了研究肌细胞祖细胞的分化,我们使用了工程化人类胚胎干细胞的克隆扩增。嘌呤霉素选择的心肌细胞表现出与成人心肌细胞相似的基因表达谱,并产生与正常胎儿心肌细胞一致的力和动作电位。这些结果表明细胞外硬度显着影响未成熟心室肌细胞的成熟和分化。
The maturation of cardiac myocytes during the immediate prenatal period coincides with changes in the mechanical properties of the extracellular matrix. We investigated the effects of extracellular stiffness on cardiomyocyte maturation in neonatal rat ventricular myocytes grown on collagen-coated gels. Cells on 10 kPa substrates developed aligned sarcomeres, while cells on stiffer substrates had unaligned sarcomeres and stress fibers. Cells generated greater mechanical force on gels with stiffness similar to the native myocardium than on stiffer or softer substrates. To investigate the differentiation of myocyte progenitors, we used clonal expansion of engineered human embryonic stem cells. Puromycin-selected cardiomyocytes exhibited a gene expression profile similar to that of adult human cardiomyocytes and generated force and action potentials consistent with normal fetal cardiomyocytes. These results suggest extracellular stiffness significantly affects maturation and differentiation of immature ventricular myocytes.
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