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Abstract：
Cellular reprogramming technologies have been developed with different physicochemical factors to improve the reprogramming efficiencies of induced pluripotent stem cells (iPSCs). Ultrasound is a clinically applied noncontact biophysical factor known for regulating various cellular behaviors but remains uninvestigated for cellular reprogramming. Here, we present a new reprogramming strategy using low-intensity ultrasound (LIUS) to improve cellular reprogramming of iPSCs in vitro and in vivo. Under 3D microenvironment conditions, increased LIUS stimulation shows enhanced cellular reprogramming of the iPSCs. The cellular reprogramming process facilitated by LIUS is accompanied by increased mesenchymal to epithelial transition and histone modification. LIUS stimulation transiently modulates the cytoskeletal rearrangement, along with increased membrane fluidity and mobility to increase HA/CD44 interactions. Furthermore, LIUS stimulation with HA hydrogel can be utilized in application of both human cells and in vivo environment, for enhanced reprogrammed cells into iPSCs. Thus, LIUS stimulation with a combinatorial 3D microenvironment system can improve cellular reprogramming in vitro and in vivo environments, which can be applied in various biomedical fields.
摘要：
已经开发了具有不同物理化学因素的细胞重编程技术,以提高诱导多能干细胞(iPSC)的重编程效率。超声是一种临床应用的非接触生物物理因子，已知用于调节各种细胞行为，但仍未对细胞重编程进行研究。这里,我们提出了一种新的使用低强度超声（LIUS）的重编程策略，以改善体外和体内iPSCs的细胞重编程。在三维微环境条件下，增加的LIUS刺激显示iPSC的细胞重编程增强。LIUS促进的细胞重编程过程伴随着间充质向上皮转化和组蛋白修饰的增加。LIUS刺激瞬时调节细胞骨架重排，随着膜流动性和流动性的增加，增加HA/CD44相互作用。此外，具有HA水凝胶的LIUS刺激可用于人细胞和体内环境的应用，用于增强的重编程细胞进入iPSC。因此，使用组合3D微环境系统进行LIUS刺激可以改善体外和体内环境中的细胞重编程，可应用于各种生物医学领域。
