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High-efficiency quantitative control of mitochondrial transfer based on droplet microfluidics and its application on muscle regeneration
Science Advances ( IF 11.7 ) Pub Date : 2022-08-17 , DOI: 10.1126/sciadv.abp9245
Jiayu Sun 1 , Hiu Tung Jessica Lo 2, 3, 4 , Lei Fan 1 , Tsz Lam Yiu 2, 3, 4 , Adnan Shakoor 1 , Gang Li 2, 3, 4 , Wayne Y W Lee 2, 3, 4, 5 , Dong Sun 1, 6
Affiliation  

Mitochondrial transfer is a spontaneous process to restore damaged cells in various pathological conditions. The transfer of mitochondria to cell therapy products before their administration can enhance therapeutic outcomes. However, the low efficiency of previously reported methods limits their clinical application. Here, we developed a droplet microfluidics–based mitochondrial transfer technique that can achieve high-efficiency and high-throughput quantitative mitochondrial transfer to single cells. Because mitochondria are essential for muscles, myoblast cells and a muscle injury model were used as a proof-of-concept model to evaluate the proposed technique. In vitro and in vivo experiments demonstrated that C2C12 cells with 31 transferred mitochondria had significant improvements in cellular functions compared to those with 0, 8, and 14 transferred mitochondria and also had better therapeutic effects on muscle regeneration. The proposed technique can considerably promote the clinical application of mitochondrial transfer, with optimized cell function improvements, for the cell therapy of mitochondria-related diseases.

中文翻译:

基于液滴微流控的线粒体高效定量控制及其在肌肉再生中的应用

线粒体转移是在各种病理条件下恢复受损细胞的自发过程。在给药之前将线粒体转移到细胞治疗产品中可以提高治疗效果。然而,先前报道的方法的低效率限制了它们的临床应用。在这里,我们开发了一种基于液滴微流体的线粒体转移技术,可以实现高效、高通量的线粒体定量转移至单细胞。由于线粒体对肌肉至关重要,因此成肌细胞和肌肉损伤模型被用作概念验证模型来评估所提出的技术。体外和体内实验表明,具有 31 个转移线粒体的 C2C12 细胞与具有 0、8、14个转移线粒体对肌肉再生也有较好的治疗作用。所提出的技术可以显着促进线粒体转移的临床应用,优化细胞功能改善,用于线粒体相关疾病的细胞治疗。
更新日期:2022-08-17
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