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健康和萎缩性 3-D 生物工程骨骼肌组织的电生理分析。

Electrophysiological analysis of healthy and dystrophic 3-D bioengineered skeletal muscle tissues.

机构信息

Department of Biology, University of Toronto Mississauga, Toronto, Canada.

Department of Cell and Systems Biology, University of Toronto, Toronto, Canada.

出版信息

Am J Physiol Cell Physiol. 2021 Oct 1;321(4):C749-C759. doi: 10.1152/ajpcell.00049.2021. Epub 2021 Aug 18.

Abstract

Recently, methods for creating three-dimensional (3-D) human skeletal muscle tissues from myogenic cell lines have been reported. Bioengineered muscle tissues are contractile and respond to electrical and chemical stimulation. In this study, we provide an electrophysiological analysis of healthy and dystrophic 3-D bioengineered skeletal muscle tissues, focusing on Duchenne muscular dystrophy (DMD). We enlist the 3-D in vitro model of DMD muscle tissue to evaluate muscle cell electrical properties uncoupled from presynaptic neural inputs, an understudied aspect of DMD. Our data show that previously reported electrophysiological aspects of DMD, including effects on membrane potential and membrane resistance, are replicated in the 3-D muscle tissue model. Furthermore, we test a potential therapeutic compound, poloxamer 188, and demonstrate capacity for improving the membrane potential in DMD muscle. Therefore, this study serves as a baseline for a new in vitro method to examine potential therapies for muscular disorders.

摘要

最近,已有研究报道了从成肌细胞系中创建三维(3-D)人体骨骼肌组织的方法。生物工程化的肌肉组织具有收缩性,并对电和化学刺激作出反应。在这项研究中,我们对健康和肌营养不良症的 3-D 生物工程化骨骼肌组织进行了电生理学分析,重点研究杜氏肌营养不良症(DMD)。我们利用 DMD 肌肉组织的 3-D 体外模型来评估肌肉细胞的电特性,这些特性与突触前神经输入解耦,这是 DMD 研究中一个未被充分研究的方面。我们的数据表明,之前报道的 DMD 的电生理学方面,包括对膜电位和膜电阻的影响,在 3-D 肌肉组织模型中得到了复制。此外,我们测试了一种潜在的治疗化合物,泊洛沙姆 188,并证明其有能力改善 DMD 肌肉的膜电位。因此,这项研究为一种新的体外方法提供了基础,可用于研究治疗肌肉疾病的潜在疗法。

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