Disease Biophysics Group, Harvard Stem Cell Institute, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Biomaterials. 2010 May;31(13):3613-21. doi: 10.1016/j.biomaterials.2010.01.079. Epub 2010 Feb 9.
In vitro cardiovascular disease models need to recapitulate tissue-scale function in order to provide in vivo relevance. We have developed a new method for measuring the contractility of engineered cardiovascular smooth and striated muscle in vitro during electrical and pharmacological stimulation. We present a growth theory-based finite elasticity analysis for calculating the contractile stresses of a 2D anisotropic muscle tissue cultured on a flexible synthetic polymer thin film. Cardiac muscle engineered with neonatal rat ventricular myocytes and paced at 0.5 Hz generated stresses of 9.2 +/- 3.5 kPa at peak systole, similar to measurements of the contractility of papillary muscle from adult rats. Vascular tissue engineered with human umbilical arterial smooth muscle cells maintained a basal contractile tone of 13.1 +/- 2.1 kPa and generated another 5.1 +/- 0.8 kPa when stimulated with endothelin-1. These data suggest that this method may be useful in assessing the efficacy and safety of pharmacological agents on cardiovascular tissue.
在体心血管疾病模型需要再现组织尺度的功能,以提供体内相关性。我们开发了一种新的方法,用于在电和药理学刺激下测量工程心血管平滑肌和横纹肌的收缩性。我们提出了一种基于生长理论的有限弹性分析,用于计算在柔性合成聚合物薄膜上培养的二维各向异性肌肉组织的收缩应力。用新生大鼠心室肌细胞工程化并以 0.5 Hz 的频率起搏,在收缩期峰值产生 9.2 +/- 3.5 kPa 的应力,类似于成年大鼠乳头肌收缩性的测量值。用人脐动脉平滑肌细胞工程化的血管组织维持 13.1 +/- 2.1 kPa 的基础收缩张力,当用内皮素-1 刺激时产生另外 5.1 +/- 0.8 kPa 的张力。这些数据表明,该方法可能有助于评估心血管组织中药物的疗效和安全性。