A role for matrix stiffness in the regulation of cardiac side population cell function.
A role for matrix stiffness in the regulation of cardiac side population cell function.
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DOI：
10.1152/ajpheart.00935.2014
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发表时间：
2015-05
期刊：
影响因子：
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通讯作者：
Y. Qiu;A. F. Bayomy;M. Gomez;M. Bauer;P. Du;Yanfei Yang;Xin Zhang;R. Liao
中科院分区：
文献类型：
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作者：
Y. Qiu;A. F. Bayomy;M. Gomez;M. Bauer;P. Du;Yanfei Yang;Xin Zhang;R. Liao
局部微环境的机械特性可能对成体组织祖细胞的命运和功能产生重要影响，改变再生过程。这在心肌梗塞后尤其重要，其中正常的、顺应性的心肌组织被纤维化的、僵硬的疤痕组织所取代。在这项研究中，我们研究了基质硬度对成人心脏侧群（CSP）祖细胞行为的影响。分离绵羊和鼠类 CSP 细胞并在聚二甲基硅氧烷基质上培养，复制正常和纤维化心肌的弹性模量。在硬质基质上培养的 CSP 细胞的增殖能力和细胞周期增加，伴随着心肌分化的减少和细胞老化的加速。此外，硬基质上的培养刺激了 CSP 细胞中细胞外基质和粘附蛋白基因表达的上调。总的来说，我们证明了微环境特性，包括基质刚度，在调节内源性 CSP 细胞的祖细胞功能中发挥着关键作用。了解组织微环境对驻留心脏祖细胞的影响是实现功能性心脏再生的关键一步。
The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration.