Engineered heart slices for electrophysiological and contractile studies.
Engineered heart slices for electrophysiological and contractile studies.
复制标题
DOI：
10.1016/j.biomaterials.2015.03.026
复制
发表时间：
2015-07
期刊：
影响因子：
14
通讯作者：
Tung L
中科院分区：
文献类型：
--
作者：
Blazeski A;Kostecki GM;Tung L
为了忠实地表现生理行为，设计工程心脏组织时的一个主要考虑因素是再现天然组织的复杂地形和生物化学。在这项研究中，我们提出了工程心脏切片（EHS），它将新生大鼠心室细胞（NRVC）接种到脱细胞心脏组织的薄片上，保留了天然细胞外基质（ECM）的重要方面。为了形成 EHS，将大鼠或猪的心室组织切成 300 µm 厚、5 至 16 mm 直径的圆盘，随后使用去污剂将其脱细胞，铺在盖玻片上，并接种 NRVC。 ECM 的有组织的纤维结构在去细胞化后仍然存在，并促进细胞伸长和排列，从而形成可以进行电调速的各向异性功能组织。起搏速率较高时收缩减少，光学测绘显示电传导呈各向异性，比率约为 2.0、动作电位的速率依赖性缩短和传导减慢，以及利多卡因（钠通道阻滞剂）引起的传导减慢。折返性心律失常也可以通过起搏诱发和终止。 EHS 构成了一种有吸引力的体外心脏组织，其中心脏细胞在脱细胞心脏 ECM 薄片上培养，提供传统细胞培养物中不存在的重要生化、结构和机械线索。
A major consideration in the design of engineered cardiac tissues for the faithful representation of physiological behavior is the recapitulation of the complex topography and biochemistry of native tissue. In this study we present engineered heart slices (EHS), which seed neonatal rat ventricular cells (NRVCs) onto thin slices of decellularized cardiac tissue that retain important aspects of native extracellular matrix (ECM). To form EHS, rat or pig ventricular tissue was sectioned into 300 µm-thick, 5 to 16 mm-diameter disks, which were subsequently decellularized using detergents, spread on coverslips, and seeded with NRVCs. The organized fiber structure of the ECM remained after decellularization and promoted cell elongation and alignment, resulting in an anisotropic, functional tissue that could be electrically paced. Contraction decreased at higher pacing rates, and optical mapping revealed electrical conduction that was anisotropic with a ratio of approximately 2.0, rate-dependent shortening of the action potential and slowing of conduction, and lidocaine (sodium channel blocker)-induced slowing of conduction. Reentrant arrhythmias could also be pace-induced and terminated. EHS constitute an attractive in vitro cardiac tissue in which cardiac cells are cultured on thin slices of decellularized cardiac ECM that provide important biochemical, structural, and mechanical cues absent in traditional cell cultures.