Song Ki-Young, Correia Jorge C, Ruas Jorge L, Teixeira Ana I
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
The School of Mechatronical Engineering, Beijing Institute of Technology, Beijing, China.
Biotechnol Bioeng. 2021 Jun;118(6):2234-2242. doi: 10.1002/bit.27731. Epub 2021 Apr 6.
Microfluidic-based technologies enable the development of cell culture systems that provide tailored microenvironmental inputs to mammalian cells. Primary myoblasts can be induced to differentiate into multinucleated skeletal muscle cells, myotubes, which are a relevant model system for investigating skeletal muscle metabolism and physiology in vitro. However, it remains challenging to differentiate primary myoblasts into mature myotubes in microfluidics devices. Here we investigated the effects of integrating continuous (solid) and intermittent (dashed) walls in microfluidic channels as topological constraints in devices designed to promote the alignment and maturation of primary myoblast-derived myotubes. The topological constraints caused alignment of the differentiated myotubes, mimicking the native anisotropic organization of skeletal muscle cells. Interestingly, dashed walls facilitated the maturation of skeletal muscle cells, as measured by quantifying myotube cell area and the number of nuclei per myotube. Together, our results suggest that integrating dashed walls as topographic constraints in microfluidic devices supports the alignment and maturation of primary myoblast-derived myotubes.
基于微流控的技术能够开发出可为哺乳动物细胞提供定制化微环境输入的细胞培养系统。原代成肌细胞可被诱导分化为多核骨骼肌细胞，即肌管，这是用于体外研究骨骼肌代谢和生理学的相关模型系统。然而，在微流控装置中将原代成肌细胞分化为成熟肌管仍具有挑战性。在此，我们研究了在微流控通道中整合连续（实线）和间断（虚线）壁作为拓扑约束对旨在促进原代成肌细胞来源的肌管排列和成熟的装置的影响。拓扑约束导致分化的肌管排列，模拟了骨骼肌细胞天然的各向异性组织。有趣的是，通过量化肌管细胞面积和每个肌管的核数量来衡量，虚线壁促进了骨骼肌细胞的成熟。总之，我们的结果表明，在微流控装置中整合虚线壁作为地形约束可支持原代成肌细胞来源的肌管的排列和成熟。
