The stimulation of the cardiac differentiation of mesenchymal stem cells in tissue constructs that mimic myocardium structure and biomechanics.
The stimulation of the cardiac differentiation of mesenchymal stem cells in tissue constructs that mimic myocardium structure and biomechanics.
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DOI：
10.1016/j.biomaterials.2011.04.038
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发表时间：
2011-08
期刊：
影响因子：
14
通讯作者：
Moldovan, Nicanor I.
中科院分区：
文献类型：
--
作者：
Guan, Jianjun;Wang, Feng;Li, Zhenqing;Chen, Joseph;Guo, Xiaolei;Liao, Jun;Moldovan, Nicanor I.
我们研究了与心肌的结构和机械特性相似的组织结构是否会诱导间充质干细胞(MSCs)分化为心脏谱系，以及进一步模仿心肌的三维细胞排列是否会促进心脏分化。组织结构是通过将骨髓间充质干细胞与弹性聚氨酯纳米纤维在电场中整合而产生的。工艺参数的控制导致了组织结构重现纤维结构和各向异性结构，以及天然猪心肌的典型应力-应变响应。动态培养时，MSCs在组织结构中增殖，但仍保持圆形形态。MRNA的表达显示心脏分化受到明显刺激。通过组织结构内间充质干细胞的三维排列来增强心脏分化。细胞对齐是通过在培养过程中静态拉伸组织结构来实现的。拉伸应变从25%增加到75%会增加细胞的三维排列程度。实时定量RT-PCR结果显示，当细胞呈高度排列时(应用75%的菌株)，其心脏标志物(GATA4、NKX2.5和MEF2C)的表达显著增加。分化的细胞还发展了钙通道，这是必须具有电生理特性的。这份报告在一定程度上解释了许多体内研究的结果，其中只有有限数量的注射的MSCs分化为心肌细胞。可能是心跳的压力(∼20%)不能使MSCs具有足够高的排列，从而实现显著的心脏分化。这项工作表明，在注射前将MSCs预分化为心肌细胞可能比简单地将未分化的MSCs注射到心脏中可能导致更大程度的心脏再生。
We investigated whether tissue constructs resembling structural and mechanical properties of the myocardium would induce mesenchymal stem cells (MSCs) to differentiate into a cardiac lineage, and whether further mimicking the 3-D cell alignment of myocardium would enhance cardiac differentiation. The tissue constructs were generated by integrating MSCs with elastic polyurethane nanofibers in an electrical field. Control of processing parameters resulted in tissue constructs recapitulating the fibrous and anisotropic structure, and typical stress-strain response of native porcine myocardium. MSCs proliferated in the tissue constructs when cultured dynamically, but retained a round morphology. mRNA expression demonstrated that cardiac differentiation was significantly stimulated. Enhanced cardiac differentiation was achieved by 3-D alignment of MSCs within the tissue constructs. Cell alignment was attained by statically stretching tissue constructs during culture. Increasing stretching strain from 25% to 75% increased the degree of 3-D cell alignment. Real time RT-PCR results showed that when cells assuming a high degree of alignment (with application of 75% strain), their expression of cardiac markers (GATA4, Nkx2.5 and MEF2C) remarkably increased. The differentiated cells also developed calcium channels, which are required to have electrophysiological properties. This report to some extent explains the outcome of many in vivo studies, where only a limited amount of the injected MSCs differentiated into cardiomyocytes. It is possible that the strain of the heartbeat (∼20%) cannot allow the MSCs to have an alignment high enough for a remarkable cardiac differentiation. This work suggests that pre-differentiation of MSCs into cardiomyocytes prior to injection may result in a greater degree of cardiac regeneration than simply injecting un-differentiated MSCs into heart.
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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
影响因子：
29.4
作者：
Amoroso, Nicholas J.;D'Amore, Antonio;Hong, Yi;Wagner, William R.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
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
DOI：
10.1073/pnas.0812242106
发表时间：
2009-09-01
影响因子：
11.1
作者：
Dvir, Tal;Kedem, Alon;Cohen, Smadar
通讯作者：
Cohen, Smadar
影响因子：
14
作者：
Huang, Chieh-Cheng;Liao, Chen-Kang;Sung, Hsing-Wen
通讯作者：
Sung, Hsing-Wen