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Mechanobiologically-Activated, Scaffold-free Transplantation of Stem cells to Repair Injured Cardiac Tissues

机译:机械生物学活化的无支架干细胞移植修复受损的心脏组织。

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We have successfully designed a biomimetic system that closely mimics the native mechanical stimulation generated by CMs. The cyclic strain provided by the rhythmic beating allowed for the modulation of the genetic profile of hASCs. Specifically, we found an upregulation of mechano-transduction genes such as YAP1 and TAZ, as well as overexpression of cardiomyogenic markers as observed in the metatranscriptomic analysis. These findings are indicative of a direct correlation between this mechanical stimulus and cardiomyogenic differentiation of hASCs. Finally, upon transplantation of the pre-conditioned hASCs into AMI mice model, we observed an improvement in cardiac function and increased angiogenesis in the peri-infarct region after 21 days (Figure 1). Overall, these findings indicate that cyclic strain provided by the designed biomimetic system is an essential stimulant for hASCs cardiomyogenic differentiation, and therefore can be a potential solution to improve stem-cell based efficacy for cardiovascular repair without using any scaffold or carrier.
机译:我们已经成功设计了一种仿生系统,该系统可以模仿CM产生的自然机械刺激。有节奏的跳动所提供的周期性应变可调节hASC的遗传特征。具体而言,我们在元转录组学分析中发现了机械转导基因(如YAP1和TAZ)的上调,以及心肌表达标志物的过表达。这些发现表明这种机械刺激与hASCs的心肌原性分化之间存在直接的相关性。最后,将经过预处理的hASCs移植到AMI小鼠模型中后,我们观察到21天后心梗周围区域心脏功能的改善和血管生成的增加(图1)。总体而言,这些发现表明,所设计的仿生系统提供的循环应变是hASCs心肌分化的基本刺激因素,因此可以成为无需使用任何支架或载体即可提高基于干细胞的心血管修复功效的潜在解决方案。

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