Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies
Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies
复制标题
DOI：
10.1152/ajpheart.1999.277.2.h433
复制
发表时间：
1999-08-01
影响因子：
4.8
通讯作者：
Freed, LE
中科院分区：
文献类型：
--
作者：
Bursac, N;Papadaki, M;Freed, LE
本研究的目的是建立一个用于电生理研究的三维离体心肌模型系统。将含有较低或较高分数心肌细胞的原代新生大鼠心室细胞在生物反应器中的聚合物支架上培养，以分别形成常规或富集的心肌构建体。1周后，所有的结构包含一个外周组织样区域（50-70 μ m厚），其中分化的心肌细胞在3-D配置的多层组织。细胞大小（蛋白质/DNA）和代谢活性（四唑转化/DNA）的指数是相似的结构和新生大鼠心室。使用细胞外电极的线性阵列进行的电生理学研究表明，结构的外围区域表现出相对均匀的电特性和持续的宏观连续脉冲传播厘米大小的规模。富集结构的电生理特性上级于常规结构的电生理特性，但劣于天然心室的电生理特性。这些结果表明，3-D心肌构建体可以被设计成具有心脏特异性结构和电生理特性，并用于体外脉冲传播研究。
The objective of this study was to establish a three-dimensional (3-D) in vitro model system of cardiac muscle for electrophysiological studies. Primary neonatal rat ventricular cells containing lower or higher fractions of cardiac myocytes were cultured on polymeric scaffolds in bioreactors to form regular or enriched cardiac muscle constructs, respectively. After 1 wk, all constructs contained a peripheral tissue-like region (50-70 mu m thick) in which differentiated cardiac myocytes were organized in multiple layers in a 3-D configuration. Indexes of cell size (protein/DNA) and metabolic activity (tetrazolium conversion/DNA) were similar for constructs and neonatal rat ventricles. Electrophysiological studies conducted using a linear array of extracellular electrodes showed that the peripheral region of constructs exhibited relatively homogeneous electrical properties and sustained macroscopically continuous impulse propagation on a centimeter-size scale. Electrophysiological properties of enriched constructs were superior to those of regular constructs but inferior to those of native ventricles. These results demonstrate that 3-D cardiac muscle constructs can be engineered with cardiac-specific structural and electrophysiological properties and used for in vitro impulse propagation studies.