Creation of myocardial tubes using cardiomyocyte sheets and an in vitro cell sheet-wrapping device
Creation of myocardial tubes using cardiomyocyte sheets and an in vitro cell sheet-wrapping device
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DOI：
10.1016/j.biomaterials.2007.04.016
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发表时间：
2007-08-01
期刊：
影响因子：
14
通讯作者：
Okano, Teruo
中科院分区：
文献类型：
--
作者：
Kubo, Hirotsugu;Shimizu, Tatsuya;Okano, Teruo
再生医学包括注射分离细胞和移植组织工程化心肌补片，作为修复受损心肌的一种替代方法，受到了极大的关注。在本研究中，作为下一代心肌组织工程，我们展示了利用细胞片工程技术在体外制造搏动心肌管的方法。从温度响应型培养皿中获得三张新生大鼠心肌细胞片，使用一种新型的细胞片包裹装置将其包裹在纤维蛋白管周围。在细胞板包裹后3h内，管状结构呈现自发、同步的搏动。收缩力测量表明，随着静息长度的增加(启动机制)和细胞外钙离子浓度的增加，收缩力增加。此外，组织工程心肌管表现出可测量的收缩引起的内压变化(0.11+/-0.01 mm Hg，最大0.15 mm Hg，n=5)。组织学分析显示，心肌组织内有分化良好的肌节和弥漫性缝隙连接，类似于天然心肌。这些数据表明，组织工程心肌管具有天然的心脏样结构和功能。这些新的心肌组织结构应该有助于未来在生理学研究和药物筛选中的应用，并为创造能够独立辅助心脏的工程组织提供了一种可能的核心技术。(C)2007爱思唯尔有限公司。保留所有权利。
Regenerative medicine involving injection of isolated cells and transplantation of tissue-engineered myocardial patches, has received significant attention as an alternative method to repair damaged heart muscle. In the present study, as the next generation of myocardial tissue engineering we demonstrate the in vitro fabrication of pulsatile myocardial tubes using cell sheet engineering technologies. Three neonatal rat cardiomyocyte sheets, which were harvested from temperature-responsive culture dishes, were wrapped around fibrin tubes using a novel cell sheet-wrapping device. The tubular constructs demonstrated spontaneous, synchronized pulsation within 3 h after cell sheet wrapping. Contractile force measurements showed that the contractile force increased in accordance with both increasing rest length (Starling mechanism) and increasing extracellular Ca2+ concentration. Furthermore, the tissue-engineered myocardial tubes presented measurable inner pressure changes evoked by tube contraction (0.11 +/- 0.01 mmHg, max 0.15 mmHg, n = 5). Histological analyses revealed both well-differentiated sarcomeres and diffuse gap junctions within the myocardial tissues that resembled native cardiac muscle. These data indicate that tissue-engineered myocardial tubes have native heart-like structure and function. These new myocardial tissue constructs should be useful for future applications in physiological studies and pharmacological screening, and present a possible core technology for the creation of engineered tissues capable of independent cardiac assistance. (c) 2007 Elsevier Ltd. All rights reserved.