心肌细胞在分化和成熟过程中的力发展。
Cardiac myocyte force development during differentiation and maturation.
机构信息
Department of Bioengineering, Rice University, and Division of Congenital Heart Surgery, Texas Children's Hospital, Houston, Texas, USA.
出版信息
Ann N Y Acad Sci. 2010 Feb;1188:121-7. doi: 10.1111/j.1749-6632.2009.05091.x.
Abstract
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 that of 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 that extracellular stiffness significantly affects maturation and differentiation of immature ventricular myocytes.
摘要
在即刻产前期间，心肌细胞的成熟与细胞外基质机械性能的变化相吻合。我们研究了细胞外基质硬度对在胶原蛋白包被凝胶上生长的新生大鼠心室肌细胞成熟的影响。在 10kPa 基质上的细胞形成了排列整齐的肌节，而在更硬基质上的细胞则形成了未对齐的肌节和应力纤维。与更硬或更软的基质相比，细胞在与天然心肌相似的硬度的凝胶上产生更大的机械力。为了研究心肌前体细胞的分化，我们利用工程化人类胚胎干细胞的克隆扩增。经嘌呤霉素选择的心肌细胞表现出与成年人类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，细胞外基质硬度显著影响未成熟心室肌细胞的成熟和分化。
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