High-throughput, real-time monitoring of engineered skeletal muscle function using magnetic sensing.

High-throughput, real-time monitoring of engineered skeletal muscle function using magnetic sensing.
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DOI:
10.1177/20417314221122127
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发表时间:
2022-01
影响因子:
8.2
通讯作者:
Mack, David L.
Mack, David L.
中科院分区:
工程技术1区
文献类型:
--
作者:
Smith, Alec S. T.;Luttrell, Shawn M.;Dupont, Jean-Baptiste;Gray, Kevin;Lih, Daniel;Fleming, Jacob W.;Cunningham, Nathan J.;Jepson, Sofia;Hesson, Jennifer;Mathieu, Julie;Maves, Lisa;Berry, Bonnie J.;Fisher, Elliot C.;Sniadecki, Nathan J.;Geisse, Nicholas A.;Mack, David L.

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工程化肌肉组织是检测骨骼肌组织水平收缩特性的有力工具。然而,与标准分析方法相关的通量的限制限制了其用于纵向研究、高通量药物筛选和疾病建模的效用。在这里,我们提出了一种将3D工程化骨骼肌与磁传感系统相结合的方法,以促进对收缩动力学的非侵入性纵向分析。使用这个平台,我们表明,来自诱导多能干细胞和初级来源的工程化骨骼肌组织在培养中随着时间的推移收缩输出得到改善。我们演示了如何磁感应收缩性可以同时评估多个组织进行不同剂量的已知骨骼肌正性肌力药物,以及分层的健康与患病的功能配置文件在正常和营养不良的肌肉细胞。基于这些数据,这种组合的培养系统和基于磁体的收缩性平台极大地拓宽了3D工程化骨骼肌组织的潜力,从而影响了从实验室到临床的新型疗法的转化。
Engineered muscle tissues represent powerful tools for examining tissue level contractile properties of skeletal muscle. However, limitations in the throughput associated with standard analysis methods limit their utility for longitudinal study, high throughput drug screens, and disease modeling. Here we present a method for integrating 3D engineered skeletal muscles with a magnetic sensing system to facilitate non-invasive, longitudinal analysis of developing contraction kinetics. Using this platform, we show that engineered skeletal muscle tissues derived from both induced pluripotent stem cell and primary sources undergo improvements in contractile output over time in culture. We demonstrate how magnetic sensing of contractility can be employed for simultaneous assessment of multiple tissues subjected to different doses of known skeletal muscle inotropes as well as the stratification of healthy versus diseased functional profiles in normal and dystrophic muscle cells. Based on these data, this combined culture system and magnet-based contractility platform greatly broadens the potential for 3D engineered skeletal muscle tissues to impact the translation of novel therapies from the lab to the clinic.
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