Radisic Milica, Fast Vladimir G, Sharifov Oleg F, Iyer Rohin K, Park Hyoungshin, Vunjak-Novakovic Gordana
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Tissue Eng Part A. 2009 Apr;15(4):851-60. doi: 10.1089/ten.tea.2008.0223.
Cardiac tissue engineering has a potential to provide functional, synchronously contractile tissue constructs for heart repair, and for studies of development and disease using in vivo-like yet controllable in vitro settings. In both cases, the utilization of bioreactors capable of providing biomimetic culture environments is instrumental for supporting cell differentiation and functional assembly. In the present study, neonatal rat heart cells were cultured on highly porous collagen scaffolds in bioreactors with electrical field stimulation. A hallmark of excitable tissues such as myocardium is the ability to propagate electrical impulses. We utilized the method of optical mapping to measure the electrical impulse propagation. The average conduction velocity recorded for the stimulated constructs (14.4 +/- 4.1 cm/s) was significantly higher than that of the nonstimulated constructs (8.6 +/- 2.3 cm/s, p = 0.003). The measured electrical propagation properties correlated to the contractile behavior and the compositions of tissue constructs. Electrical stimulation during culture significantly improved amplitude of contractions, tissue morphology, and connexin-43 expression compared to the nonsimulated controls. These data provide evidence that electrical stimulation during bioreactor cultivation can improve electrical signal propagation in engineered cardiac constructs.
心脏组织工程有潜力为心脏修复提供功能性、同步收缩的组织构建物,并用于在类似体内但可控的体外环境中进行发育和疾病研究。在这两种情况下,利用能够提供仿生培养环境的生物反应器对于支持细胞分化和功能组装至关重要。在本研究中,新生大鼠心脏细胞在生物反应器中置于具有电场刺激的高度多孔胶原支架上进行培养。像心肌这样的可兴奋组织的一个标志是能够传播电冲动。我们利用光学映射方法来测量电冲动传播。记录的受刺激构建物的平均传导速度(14.4 +/- 4.1厘米/秒)显著高于未受刺激的构建物(8.6 +/- 2.3厘米/秒,p = 0.003)。所测量的电传播特性与收缩行为和组织构建物的组成相关。与未模拟的对照组相比,培养期间的电刺激显著改善了收缩幅度、组织形态和连接蛋白43的表达。这些数据证明,生物反应器培养期间的电刺激可改善工程化心脏构建物中的电信号传播。