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聚乳酸-乙醇酸共聚物底物表面修饰对新生大鼠心肌细胞基因表达的调控

Modulation of gene expression in neonatal rat cardiomyocytes by surface modification of polylactide-co-glycolide substrates.

作者信息

Brown David A, Beygui Ramin E, MacLellan William R, Laks Hillel, Dunn James C Y, Wu Benjamin M

机构信息

Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, 7523 Boelter Hall, University of California, Los Angeles, California 90095, USA.

出版信息

J Biomed Mater Res A. 2005 Sep 1;74(3):419-29. doi: 10.1002/jbm.a.30344.

Abstract

Myocardial tissue engineering presents a potential treatment option for heart disease. Cardiomyocytes isolated at various stages of development retain the ability to form contractile networks in vitro, which suggests that it should be possible to reconstitute viable myocardium given the appropriate architecture, stimuli, and cardiomyogenic cell source. This study investigates the effects of modifying substrate surface energy (by plasma etching) and protein coating (by fibronectin adsorption) on neonatal rat ventricular myocyte (NRVM) function. Primary NRVMs were cultured for 96 h on modified and control films of a common degradable polymer, polylactide-co-glycolide. Cultures were analyzed for cell spreading, protein content, and mRNA expression of atrial natriuretic factor and beta-myosin heavy chain. The results demonstrate that NRVMs cultured on etched films significantly increased in spreading, myofibril development, protein content, and gene expression of atrial natriuretic factor and beta-myosin heavy chain compared with unetched films, and that this surface energy effect is overwhelmed by the addition of fibronectin. Conclusions from this study are that surface energy and protein adsorption influence the gene expression of adherent NRVMs, and may be important for modulating the function of engineered myocardium.

摘要

心肌组织工程为心脏病提供了一种潜在的治疗选择。在不同发育阶段分离的心肌细胞在体外仍保留形成收缩网络的能力,这表明在具备合适的结构、刺激和心肌生成细胞来源的情况下,重建有活力的心肌应该是可行的。本研究调查了通过等离子体蚀刻改变底物表面能以及通过纤连蛋白吸附进行蛋白质包被对新生大鼠心室肌细胞(NRVM)功能的影响。将原代NRVM在一种常见的可降解聚合物聚乳酸 - 乙醇酸的改性膜和对照膜上培养96小时。对培养物进行细胞铺展、蛋白质含量以及心房钠尿肽和β - 肌球蛋白重链的mRNA表达分析。结果表明,与未蚀刻的膜相比,在蚀刻膜上培养的NRVM在铺展、肌原纤维发育、蛋白质含量以及心房钠尿肽和β - 肌球蛋白重链的基因表达方面均显著增加,并且这种表面能效应会被纤连蛋白的添加所掩盖。本研究的结论是,表面能和蛋白质吸附会影响贴壁NRVM的基因表达,并且可能对调节工程化心肌的功能很重要。

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