Combinatorial polymer electrospun matrices promote physiologically-relevant cardiomyogenic stem cell differentiation.
Combinatorial polymer electrospun matrices promote physiologically-relevant cardiomyogenic stem cell differentiation.
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DOI：
10.1371/journal.pone.0028935
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sung HJ
中科院分区：
文献类型：
--
作者：
Gupta MK;Walthall JM;Venkataraman R;Crowder SW;Jung DK;Yu SS;Feaster TK;Wang X;Giorgio TD;Hong CC;Baudenbacher FJ;Hatzopoulos AK;Sung HJ
心肌梗塞导致广泛的心肌细胞死亡，从而导致致命的心律失常或充血性心力衰竭。输送干细胞来重新填充受损的心脏组织可能是修复受损心脏的一种有吸引力且创新的解决方案。具有多种特性的指导性聚合物支架已被广泛用于指导干细胞的分化。在这项研究中，我们优化了电纺聚合物网的化学和机械性能，用于胚胎干细胞（ESC）向心肌细胞谱系的定向分化。通过以不同的摩尔比共聚三个不同的亚基来制备组合聚合物库，以调节所得聚合物的物理化学性质：亲水性聚乙二醇（PEG）、疏水性聚（ε-己内酯）（PCL）和带负电的羧化PCL（CPCL）。在电纺聚合物支架上培养小鼠 ESC，并通过测量活力、细胞内活性氧 (ROS)、α-肌球蛋白重链表达 (α-MHC) 和细胞内 Ca2+ 信号动力学来评估其向心肌细胞的分化。有趣的是，在最顺应的基质 4%PEG-86%PCL-10%CPCL 上的 ESC 表现出最高的 α-MHC 表达以及最成熟的 Ca2+ 信号动力学。为了研究支架模量在 ESC 分化中的作用，通过改变静电纺丝参数来降低支架纤维密度。研究发现，降低的模量可以增强 α-MHC 基因表达，并促进肌细胞 Ca2+ 处理的成熟。这些数据表明，通过共聚和静电纺丝技术调节聚合物支架的机械和化学性能，可以促进 ESC 衍生的心肌细胞分化和成熟。
Myocardial infarction results in extensive cardiomyocyte death which can lead to fatal arrhythmias or congestive heart failure. Delivery of stem cells to repopulate damaged cardiac tissue may be an attractive and innovative solution for repairing the damaged heart. Instructive polymer scaffolds with a wide range of properties have been used extensively to direct the differentiation of stem cells. In this study, we have optimized the chemical and mechanical properties of an electrospun polymer mesh for directed differentiation of embryonic stem cells (ESCs) towards a cardiomyogenic lineage. A combinatorial polymer library was prepared by copolymerizing three distinct subunits at varying molar ratios to tune the physicochemical properties of the resulting polymer: hydrophilic polyethylene glycol (PEG), hydrophobic poly(ε-caprolactone) (PCL), and negatively-charged, carboxylated PCL (CPCL). Murine ESCs were cultured on electrospun polymeric scaffolds and their differentiation to cardiomyocytes was assessed through measurements of viability, intracellular reactive oxygen species (ROS), α-myosin heavy chain expression (α-MHC), and intracellular Ca2+ signaling dynamics. Interestingly, ESCs on the most compliant substrate, 4%PEG-86%PCL-10%CPCL, exhibited the highest α-MHC expression as well as the most mature Ca2+ signaling dynamics. To investigate the role of scaffold modulus in ESC differentiation, the scaffold fiber density was reduced by altering the electrospinning parameters. The reduced modulus was found to enhance α-MHC gene expression, and promote maturation of myocyte Ca2+ handling. These data indicate that ESC-derived cardiomyocyte differentiation and maturation can be promoted by tuning the mechanical and chemical properties of polymer scaffold via copolymerization and electrospinning techniques.
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影响因子：
5
作者：
Etzion, S;Battler, A;Leor, J
通讯作者：
Leor, J
影响因子：
5.3
作者：
Hammon M;Herrmann M;Bleiziffer O;Pryymachuk G;Andreoli L;Munoz LE;Amann KU;Mondini M;Gariglio M;Airó P;Schellerer VS;Hatzopoulos AK;Horch RE;Kneser U;Stürzl M;Naschberger E
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影响因子：
5.2
作者：
Forte, Giancarlo;Carotenuto, Felicia;Di Nardo, Paolo
通讯作者：
Di Nardo, Paolo
影响因子：
3.7
作者：
Hao J;Daleo MA;Murphy CK;Yu PB;Ho JN;Hu J;Peterson RT;Hatzopoulos AK;Hong CC
通讯作者：
Hong CC