Introduction

Stem cell-based therapies represent a valid approach to restore cardiac function due to their beneficial effect in reducing scar area formation and promoting angiogenesis. However, their translation into the clinic is limited by the poor differentiation and inability to secrete sufficient therapeutic factors. To address this issue, several strategies such as genetic modification and biophysical pre-conditioning have been used to enhance the efficacy of stem cells for cardiac tissue repair.

Methods

In this study, a biomimetic approach was used to mimic the natural mechanical stimulation of the myocardium tissue. Specifically, human adipose-derived stem cells (hASCs) were cultured on a thin gelatin methacrylamide (GelMA) hydrogel disc and placed on top of a beating cardiomyocyte layer. qPCR studies and metatranscriptomic analysis of hASCs gene expression were investigated to confirm the correlation between mechanical stimuli and cardiomyogenic differentiation. In vivo intramyocardial delivery of pre-conditioned hASCs was carried out to evaluate their efficacy to restore cardiac function in mice hearts post-myocardial infarction.

Results

The cyclic strain generated by cardiomyocytes significantly upregulated the expression of both mechanotransduction and cardiomyogenic genes in hASCs as compared to the static control group. The inherent angiogenic secretion profile of hASCs was not hindered by the mechanical stimulation provided by the designed biomimetic system. Finally, in vivo analysis confirmed the regenerative potential of the pre-conditioned hASCs by displaying a significant improvement in cardiac function and enhanced angiogenesis in the peri-infarct region.

Conclusion

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.

中文翻译：

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在仿生环境中预处理干细胞以增强心脏组织修复：体外和体内分析。

介绍

基于干细胞的疗法代表了恢复心脏功能的有效方法，因为它们在减少疤痕区域形成和促进血管生成方面具有有益作用。然而，由于分化差和无法分泌足够的治疗因子，它们的临床应用受到限制。为了解决这个问题，已经使用了几种策略，例如基因改造和生物物理预处理来增强干细胞对心脏组织修复的功效。

方法

在这项研究中，使用仿生方法来模拟心肌组织的自然机械刺激。具体来说，人类脂肪干细胞 (hASCs) 在薄的明胶甲基丙烯酰胺 (GelMA) 水凝胶盘上培养，并放置在跳动的心肌细胞层的顶部。对 hASCs 基因表达的 qPCR 研究和宏转录组学分析进行了研究，以确认机械刺激与心肌分化之间的相关性。进行了预处理的 hASC 的体内心肌内递送，以评估它们在心肌梗塞后恢复小鼠心脏心脏功能的功效。

结果

与静态对照组相比，心肌细胞产生的循环应变显着上调了 hASCs 中机械转导和心肌基因的表达。hASCs 固有的血管生成分泌谱不受所设计的仿生系统提供的机械刺激的阻碍。最后，体内分析通过显示心脏功能显着改善和梗死周围区域血管生成增强，证实了预处理 hASCs 的再生潜力。

结论

总体而言，这些研究结果表明，设计的仿生系统提供的循环应变是 hASCs 心肌分化的重要刺激物，因此可以成为提高基于干细胞的心血管修复功效的潜在解决方案。