Vandenburgh Herman, Shansky Janet, Benesch-Lee Frank, Barbata Victoria, Reid Jonathan, Thorrez Lieven, Valentini Robert, Crawford Gregory
Department of Pathology, RISE Research Building, Brown Medical School/Miriam Hospital, Providence, RI 02906, USA.
Muscle Nerve. 2008 Apr;37(4):438-47. doi: 10.1002/mus.20931.
A tissue-based approach to in vitro drug screening allows for determination of the cumulative positive and negative effects of a drug at the tissue rather than the cellular or subcellular level. Skeletal muscle myoblasts were tissue-engineered into three-dimensional muscle with parallel myofibers generating directed forces. When grown attached to two flexible micro-posts (mu posts) acting as artificial tendons in a 96-well plate format, the miniature bioartificial muscles (mBAMs) generated tetanic (active) forces upon electrical stimulation measured with a novel image-based motion detection system. mBAM myofiber hypertrophy and active force increased in response to insulin-like growth factor 1. In contrast, mBAM deterioration and weakness was observed with a cholesterol-lowering statin. The results described in this study demonstrate the integration of tissue engineering and biomechanical testing into a single platform for the screening of compounds affecting muscle strength.
一种基于组织的体外药物筛选方法能够在组织水平而非细胞或亚细胞水平确定药物的累积正负效应。骨骼肌成肌细胞被组织工程化为具有平行肌纤维并产生定向力的三维肌肉。当附着生长在充当人工肌腱的两个柔性微柱（μ柱）上，以96孔板形式存在时，微型生物人工肌肉（mBAM）在通过新型基于图像的运动检测系统测量的电刺激下产生强直（主动）力。mBAM肌纤维肥大和主动力会因胰岛素样生长因子1而增加。相比之下，使用降胆固醇他汀类药物时会观察到mBAM退化和无力。本研究中描述的结果表明，组织工程和生物力学测试已整合到一个单一平台中，用于筛选影响肌肉力量的化合物。
