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Thermosensitive, Stretchable, and Piezoelectric Substrate for Generation of Myogenic Cell Sheet Fragments from Human Mesenchymal Stem Cells for Skeletal Muscle Regeneration
Advanced Functional Materials ( IF 19.0 ) Pub Date : 2017-11-09 , DOI: 10.1002/adfm.201703853
Jeong-Kee Yoon 1 , Mirnmoy Misra 2 , Seung Jung Yu 3 , Han Young Kim 1 , Suk Ho Bhang 4 , Seuk Young Song 1 , Ju-Ro Lee 1 , Seungmi Ryu 1 , Yeon Woong Choo 1 , Gun-Jae Jeong 1 , Sung Pil Kwon 1 , Sung Gap Im 3 , Tae Il Lee 2 , Byung-Soo Kim 1, 5
Affiliation  

In a native muscle microenvironment, electrical and mechanical stimuli exist in the form of action potentials and muscle contraction. Here, a cell culture system is developed that can mimic the in vivo microenvironment and provide these stimuli to cultured cells, and it is tested whether the stimulation can promote myogenic differentiation of human umbilical cord blood mesenchymal stem cells (hUCBMSCs). A thermosensitive, stretchable, and piezoelectric substrate (TSPS) is fabricated by polydimethylsiloxane spin‐coating of aligned ZnO nanorods and subsequent poly(N‐isopropylacrylamide) grafting on the polydimethylsiloxane surface. Pulsatile mechanoelectrical cues are provided to hUCBMSCs cultured on the TSPS by subjecting the TSPS to cyclic stretching and bending, resulting in significant promotion of myogenic differentiation of hUCBMSCs as well as intracellular signaling related to the differentiation. After differentiation ex vivo, the cells are detached from the TSPS in the form of cell sheet fragments. Injection of the cell sheet fragments of differentiated cells into injured mouse skeletal muscle shows improved cell retention and muscle regeneration as compared to injection of either undifferentiated cells or differentiated dissociated cells. This system may serve as a tool for research on the electrical and mechanical regulation of stem cells and may be used to potentiate stem cell therapies.

中文翻译:

热敏性,可拉伸和压电基板,用于从人间充质干细胞生成用于骨骼肌再生的成肌细胞片片段。

在天然肌肉微环境中,电和机械刺激以动作电位和肌肉收缩的形式存在。在这里,开发了可以模拟体内微环境并向培养的细胞提供这些刺激的细胞培养系统,并测试了该刺激是否可以促进人脐带血间充质干细胞(hUCBMSCs)的成肌分化。通过对二氧化锌纳米棒和随后的聚(N-异丙基丙烯酰胺)接枝到聚二甲基硅氧烷表面上。通过使TSPS经受周期性的拉伸和弯曲,可以向在TSPS上培养的hUCBMSCs提供多变的机电信号,从而显着促进hUCBMSCs的肌源性分化以及与分化有关的细胞内信号传导。离体分化后,细胞以细胞片片段的形式从TSPS分离。与注射未分化的细胞或分化的解离的细胞相比,将分化的细胞的细胞片片段注射到受伤的小鼠骨骼肌中显示出改善的细胞保留和肌肉再生。该系统可以用作研究干细胞的电气和机械调节的工具,并可以用于增强干细胞疗法。
更新日期:2017-11-09
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