Cardiac differentiation of cardiosphere-derived cells in scaffolds mimicking morphology of the cardiac extracellular matrix.
Cardiac differentiation of cardiosphere-derived cells in scaffolds mimicking morphology of the cardiac extracellular matrix.
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DOI：
10.1016/j.actbio.2014.04.018
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发表时间：
2014-08
影响因子：
9.7
通讯作者：
Guan J
中科院分区：
文献类型：
--
作者：
Xu Y;Patnaik S;Guo X;Li Z;Lo W;Butler R;Claude A;Liu Z;Zhang G;Liao J;Anderson PM;Guan J
干细胞治疗具有心肌梗死（MI）后心脏组织再生的潜力。再生依赖于移植干细胞的心脏分化。我们假设干细胞传递的时间决定了心脏分化的程度，因为细胞分化依赖于基质特性，如生物力学、结构和形态，而心肌细胞外基质（ECM）中的这些特性随着心肌梗死后的时间不断变化。为了阐明ECM特性与心脏分化之间的关系，我们建立了一个基于ECM模拟纤维和一种心脏祖细胞的体外模型。心球衍生细胞（cdc）。同时采用纤维静电纺丝和细胞电喷涂技术制备结构体。通过将高度柔软的水凝胶与相对坚硬的聚氨酯共混，并调节制造参数，可以获得具有相似细胞粘附性能但整体模量、单纤维模量、纤维密度和纤维排列不同的组织结构。在1周的培养期间，cdc在构建物中存活。CDC心脏分化依赖于支架模量、纤维体积分数和纤维排列。两种相对较低支架模量（~ 50-60 kPa）的构建最显著地引导了CDC向成熟心肌细胞的分化，这可以通过心肌肌钙蛋白T （cTnT）、钙通道（CACNA1c）和心肌肌球蛋白重链（MYH6）的基因表达以及心肌肌钙蛋白I （cTnI）和连接蛋白43 （CX43）的蛋白表达来证明。在这两种低模量结构中，低纤维排列和高纤维体积分数的分化程度更大。这些结果表明，心脏ECM特性可能对传递干细胞的心脏分化有影响。
Stem cell therapy has the potential to regenerate heart tissue after myocardial infarction (MI). The regeneration is dependent upon cardiac differentiation of the delivered stem cells. We hypothesized that timing of the stem cell delivery determines the extent of cardiac differentiation as cell differentiation is dependent on matrix properties such as biomechanics, structure and morphology, and these properties in cardiac extracellular matrix (ECM) continuously vary with time after MI. In order to elucidate the relationship between ECM properties and cardiac differentiation, we created an in vitro model based on ECM-mimicking fibers and a type of cardiac progenitor cell, cardiosphere-derived cells (CDCs). A simultaneous fiber electrospinning and cell electrospraying technique was utilized to fabricate constructs. By blending a highly soft hydrogel with a relatively stiff polyurethane and modulating fabrication parameters, tissue constructs with similar cell adhesion property but different global modulus, single fiber modulus, fiber density and fiber alignment were achieved. The CDCs remained alive within the constructs during a 1 week culture period. CDC cardiac differentiation was dependent on the scaffold modulus, fiber volume fraction and fiber alignment. Two constructs with relatively low scaffold modulus, ~50–60 kPa, most significantly directed the CDC differentiation into mature cardiomyocytes as evidenced by gene expressions of cardiac troponin T (cTnT), calcium channel (CACNA1c) and cardiac myosin heavy chain (MYH6), and protein expressions of cardiac troponin I (cTnI) and connexin 43 (CX43). Of these two low-modulus constructs, the extent of differentiation was greater for lower fiber alignment and higher fiber volume fraction. These results suggest that cardiac ECM properties may have an effect on cardiac differentiation of delivered stem cells.
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影响因子：
3.7
作者：
Davis DR;Zhang Y;Smith RR;Cheng K;Terrovitis J;Malliaras K;Li TS;White A;Makkar R;Marbán E
通讯作者：
Marbán E
DOI：
10.1002/jbm.10204
发表时间：
2002-09-05
期刊：
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子：
--
作者：
Guan, JJ;Sacks, MS;Wagner, WR
通讯作者：
Wagner, WR
影响因子：
46.9
作者：
Holst, Jeff;Watson, Sarah;Rasko, John E. J.
通讯作者：
Rasko, John E. J.
DOI：
10.1115/1.2354200
发表时间：
2006-12-01
影响因子：
1.7
作者：
Gilbert, Thomas W.;Sacks, Michael S.;Chancellor, Michael B.
通讯作者：
Chancellor, Michael B.
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW