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使用新型纳米纤维网的收缩性心脏移植物。

Contractile cardiac grafts using a novel nanofibrous mesh.

作者信息

Shin M, Ishii O, Sueda T, Vacanti J P

机构信息

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Wellman 627, 55 Fruit Street, Boston, MA 02114, USA.

出版信息

Biomaterials. 2004 Aug;25(17):3717-23. doi: 10.1016/j.biomaterials.2003.10.055.

Abstract

Cardiomyoctes are terminally differentiated cells and therefore unable to regenerate after infarction. The use of autologous bioengineered cardiac grafts has been suggested to replace infarcted myocardium and enhance cardiac function. Here we report the development of an in vitro system for engineered myocardium. Cardiac nanofibrous meshes (CNM) were developed by culturing cardiomyocytes from neonatal Lewis rats on electrospun, nanofibrous polycaprolactone (PCL) meshes. The mesh had an ECM-like topography and was suspended across a wire ring that acted as a passive load to contracting cardiomyocytes. The cardiomyocytes started beating after 3 days and were cultured in vitro for 14 days. The cardiomyocytes attached well on the PCL meshes and expressed cardiac-specific proteins such as alpha-myosin heavy chain, connexin43 and cardiac troponin I. The results demonstrate the formation of contractile cardiac grafts in vitro. Using this technique, cardiac grafts can be matured in vitro to obtain sufficient function prior to implantation. It is conjectured that cardiac grafts with clinically relevant dimensions can be obtained by stacking CNMs and inducing vascularization with angiogenic factors.

摘要

心肌细胞是终末分化细胞,因此在梗死之后无法再生。有人提出使用自体生物工程心脏移植物来替代梗死心肌并增强心脏功能。在此,我们报告一种用于工程化心肌的体外系统的开发。通过将新生Lewis大鼠的心肌细胞培养在静电纺丝的纳米纤维聚己内酯(PCL)网片上,开发出心脏纳米纤维网(CNM)。该网片具有类似细胞外基质的拓扑结构,并悬挂在一个金属丝环上,该金属丝环作为收缩心肌细胞的被动负载。心肌细胞在3天后开始跳动,并在体外培养14天。心肌细胞很好地附着在PCL网片上,并表达心脏特异性蛋白,如α-肌球蛋白重链、连接蛋白43和心肌肌钙蛋白I。结果证明在体外形成了收缩性心脏移植物。利用该技术,心脏移植物可在体外成熟,以便在植入前获得足够的功能。据推测,通过堆叠CNM并用血管生成因子诱导血管化,可获得具有临床相关尺寸的心脏移植物。

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